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Rev. Soc. Bras. Clín. Méd ; 18(3): 171-173, mar 2020.
Article in Portuguese | LILACS | ID: biblio-1361517


Este relato teve como objetivo apresentar um caso de elderly onset rheumatoid arthritis associada à trombocitose reacional significativa. À admissão, o paciente apresentava quadro de poliartrite de pequenas e grandes articulações associado à rigidez matinal. Após exames solicitados, evidenciaram-se trombocitose de 1.697.000 cel./mm³ e anticorpos antipeptídeos citrulinados positivos, sendo diagnosticado com artrite reumatoide do tipo elderly onset rheumatoid arthritis.

This report aimed at presenting a case of elderly-onset rheumatoid arthritis associated with significant reactive thrombocytosis. On admission, the patient presented polyarthritis of small and large joints associated with morning stiffness. After the performance of the requested tests, thrombocytosis of 1,697,000 cells/mm3 and positive anti-CCP were evidenced, and the patient was diagnosed with elderly-onset rheumatoid arthritis.

Humans , Male , Middle Aged , Arthritis, Rheumatoid/diagnosis , Thrombocytosis/diagnosis , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/blood , Rheumatoid Factor/analysis , Thrombocytosis/complications , Thrombocytosis/blood , Blood Cell Count , Blood Sedimentation , C-Reactive Protein/analysis , Edema/etiology , Anti-Citrullinated Protein Antibodies/isolation & purification
Medicina (B.Aires) ; 79(3): 161-166, June 2019. tab
Article in English | LILACS | ID: biblio-1020053


Rheumatoid arthritis is a clinical autoimmune syndrome that causes joint damage. The positive or negative anti-cyclic citrullinated protein (CCP) antibodies serodiagnosis differentiates two subsets of the disease, each with different genetic background. Previous studies have identified associations between KIR genes and rheumatoid arthritis but not with anti-CCP serodiagnosis. Therefore, we investigated the proportion of patients seropositive and seronegative to anti-CCP and its possible association with KIR (killer cell immunoglobulin-like receptor) genes. We included 100 patients with rheumatoid arthritis from western Mexico, who were determined for anti-CCP serodiagnosis by ELISA, and 16 KIR genes were genotyped by PCR-SSP. The proportion of seropositive anti-CCP patients was 83%, and they presented a higher frequency of KIR2DL2 genes than the seronegative group (73.6% vs. 46.2%, p = 0.044) which, in turn, presented a higher KIR2DL2-/ KIR2DL3+ genotype frequency than the first ones (46.2% vs. 17.2%, p = 0.043). These results suggest different KIR genetic backgrounds for each subset of the disease according to anti-CCP serodiagnosis.

La artritis reumatoide es un síndrome clínico autoinmune que causa daño en las articulaciones. El serodiagnóstico positivo o negativo para anticuerpos proteicos anti-cíclicos citrulinados (CCP) diferencia dos subconjuntos de la enfermedad, cada uno con diferente fondo genético. Estudios previos han identificado asociaciones entre los genes killer cell immunoglobulin- like receptor (KIR) y la artritis reumatoide, pero no con el serodiagnóstico de anti-CCP. Por lo tanto, investigamos la proporción de seropositividad y seronegatividad anti-CCP y su posible asociación con genes KIR. Se incluyeron 100 pacientes con artritis reumatoide del occidente de México, a quienes se les determinó su serodiagnóstico anti-CCP por ELISA y también se les realizó genotipificación de 16 genes KIR por PCR-SSP. La proporción de pacientes seropositivos anti-CCP fue del 83% y presentaron una mayor frecuencia génica KIR2DL2 que el grupo seronegativo (73.6% vs. 46.2%, p = 0.044), estos últimos presentaron mayor frecuencia genotípica KIR2DL2-/KIR2DL3+ que los primeros (46.2% vs. 17.2%, p = 0.043). Los resultados sugieren diferente fondo genético KIR para cada subconjunto de la enfermedad, de acuerdo con el serodiagnóstico anti-CCP.

Humans , Male , Female , Adult , Middle Aged , Aged , Arthritis, Rheumatoid/diagnosis , Autoantibodies/blood , Receptors, KIR2DL2/genetics , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/blood , Rheumatoid Factor/blood , Autoantibodies/genetics , Genotype , Mexico
Egyptian Journal of Hospital Medicine [The]. 2018; 71 (3): 2697-2700
in English | IMEMR | ID: emr-192518


The study aim: The purpose of this study is to measure the matrix metalloproteinase 7 [MMP7] in rheumatoid arthritis [RA] patients with interstitial lung disease [ILD] and to assess for any correlation with RA-disease activity

Research design: A cross sectional study

Sample: a purposive sample included 40 rheumatoid arthritis patients from Ain Shams University Hospitals Inpatient Department of Rheumatology and Outpatient Clinic. The results revealed that serum [S] MMP7 was significantly higher among RA patients with interstitial lung disease than patients without

Conclusion: The study documented that S.MMP7 may be used as a screening test for detection of interstitial lung disease in patients with rheumatoid arthritis

The study recommended: Measurement of serum MMP7 level to RA patients may be used as screening test for detection of ILD

Humans , Arthritis, Rheumatoid/blood , Lung Diseases, Interstitial , Cross-Sectional Studies
Säo Paulo med. j ; 135(6): 535-540, Nov.-Dec. 2017. tab
Article in English | LILACS | ID: biblio-904120


ABSTRACT BACKGROUND: Thyroid autoimmunity is more common in patients with rheumatic diseases than in healthy populations. The degree of association seems subject to influence from patients' geographical location. Here, we aimed to ascertain the prevalence of thyroid autoantibodies in a cohort of patients with systemic rheumatic disease and the degree of association between its presence and inflammatory activity. DESIGN AND SETTING: Cross-sectional observational study in a rheumatology unit. METHODS: 301 patients with systemic lupus erythematosus (SLE), 210 with rheumatoid arthritis (RA), 58 with scleroderma (SSc) and 80 with spondyloarthritis (SpA) were studied regarding thyroid function (TSH and T4), anti-thyroglobulin (TgAb) and anti-thyroperoxidase (TPOab) and compared with 141 healthy controls. Disease activity in patients with rheumatic disease was assessed through appropriate indexes. RESULTS: There were more antithyroid antibodies in SLE patients with hypothyroidism (P = 0.01; odds ratio, OR 2.7; 95% confidence interval, CI: 1.20-6.26) and in those without hypothyroidism (P = 0.06; OR 2.4; 95% CI: 1.28-4.55) than in controls. SSc patients also showed: P = 0.03 both with antithyroid antibodies and hypothyroidism (OR 3.4; 95% CI: 1.06-10.80) and without hypothyroidism (OR 3.1; 95% CI: 1.11-0.13). RA and SpA patients had the same prevalence as controls (P not significant). Presence of autoantibodies with and without hypothyroidism was not associated with the activity or functional indexes evaluated. CONCLUSION: SLE and SSc were associated with higher prevalence of thyroid autoantibodies in patients with and without hypothyroidism, unlike SpA and RA. There was no link between thyroid autoantibody presence and disease activity or functional impairment.

Humans , Male , Female , Adult , Middle Aged , Autoantibodies/blood , Autoimmune Diseases/blood , Rheumatic Diseases/blood , Iodide Peroxidase/blood , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Scleroderma, Systemic/immunology , Scleroderma, Systemic/blood , Autoantibodies/immunology , Case-Control Studies , Rheumatic Diseases/immunology , Prevalence , Cross-Sectional Studies , Spondylarthropathies/immunology , Spondylarthropathies/blood , Disability Evaluation , Iodide Peroxidase/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/blood
Rev. bras. reumatol ; 57(5): 385-391, Sept.-Oct. 2017. tab
Article in English | LILACS | ID: biblio-899442


Abstract Objectives: To correlate the basal expression of complement regulatory proteins (CRPs) CD55, CD59, CD35, and CD46 in B-lymphocytes from the peripheral blood of a cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with rituximab (RTX) with depletion and time repopulation of such cells. Methods: Ten patients with RA received two infusions of 1 g of RTX with an interval of 14 days. Immunophenotypic analysis for the detection of CD55, CD59, CD35, and CD46 on B-lymphocytes was carried out immediately before the first infusion. The population of B-lymphocytes was analyzed by means of basal CD19 expression and after 1, 2, and 6 months after the infusion of RTX, and then quarterly until clinical relapse. Depletion of B-lymphocytes in peripheral blood was defined as a CD19 expression <0.005 × 109/L. Results: Ten women with a median of 49 years and a baseline DAS28 = 5.6 were evaluated; 9 were seropositive for rheumatoid factor. Five patients showed a repopulation of B-lymphocytes after 2 months, and the other five after 6 months. There was a correlation between the basal expression of CD46 and the time of repopulation (correlation coefficient = −0.733, p = 0.0016). A similar trend was observed with CD35, but without statistical significance (correction coefficient = −0.522, p = 0.12). Conclusion: The increased CD46 expression was predictive of a faster repopulation of B-lymphocytes in patients treated with RTX. Studies involving a larger number of patients will be needed to confirm the utility of basal expression of CRPs as a predictor of clinical response.

Resumo Objetivos: Correlacionar a expressão basal das proteínas reguladoras do complemento (PRC) CD55, CD59, CD35 e CD46 nos linfócitos B do sangue periférico de uma coorte de 10 pacientes com artrite reumatoide (AR) iniciando tratamento com rituximabe (RTX) com a depleção e tempo de repopulação dessas células. Métodos: Dez pacientes com AR receberam duas infusões de 1 g de RTX com intervalo de 14 dias. Análises imunofenotípicas para detecção de CD55, CD59, CD35 e CD46 nos linfócitos B foram feitas imediatamente antes da primeira infusão. A população de linfócitos B foi analisada por meio da expressão de CD19 basal e após um, dois e seis meses após a infusão de RTX e então trimestralmente até a recaída clínica. Depleção de linfócitos B no sangue periférico foi definida como expressão de CD19 < 0,005 × 109/l. Resultados: Dez mulheres com mediana de 49 anos e DAS 28 basal de 5,6 foram avaliadas; nove eram soropositivas para o fator reumatoide. Cinco pacientes apresentaram repopulação de linfócitos B após dois meses e as outras cinco aos seis meses. Houve correlação entre a expressão basal de CD46 e o tempo de repopulação (coeficiente de correlação -0,733, p = 0,0016). Tendência semelhante foi observada com CD35, porém sem significância estatística (coeficiente de correção 0,522, p = 0,12). Conclusão: Expressão aumentada de CD46 foi preditora de repopulação mais rápida de linfócitos B em pacientes tratados com RTX. Estudos com um número maior de pacientes serão necessários para confirmar a utilidade da expressão basal das PRC como preditora de resposta clínica.

Humans , Female , Adult , Arthritis, Rheumatoid/drug therapy , B-Lymphocytes/metabolism , Antirheumatic Agents/therapeutic use , GPI-Linked Proteins/blood , Rituximab/therapeutic use , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Infusions, Intravenous , Drug Administration Schedule , B-Lymphocytes/drug effects , Biomarkers/blood , Treatment Outcome , Antirheumatic Agents/pharmacology , Rituximab/pharmacology , Middle Aged
Rev. bras. reumatol ; 57(4): 320-329, July.-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-899432


ABSTRACT Background: Systemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. Objectives: To evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease. Methods: Assessments included: body mass index, insulin resistance by Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay. Results: Outstanding results from these studies include: (1) In Rheumatoid arthritis patients, insulin resistance was well correlated with body mass index, but not with levels of serum cytokines. In fact, levels of cytokines were similar in all Rheumatoid arthritis patients, regardless of being obese, overweight or normal weight (2) Insulin resistance was significantly higher in Rheumatoid arthritis with normal weight than in normal weight (3) No significant difference was observed between insulin resistances of Rheumatoid arthritis with obesity and obesity (4) As expected, levels of circulating cytokines were significantly higher in Rheumatoid arthritis patients than in obesity. Conclusions: Obesity appears to be a dominant condition above inflammation to produce IR in RA patients. The dissociation of the inflammation and obesity components to produce IR suggests the need of an independent therapeutic strategy in obese patients with RA.

RESUMO Introdução: O bloqueio sistêmico do Fator de Necrose Tumoral-α (TNF-α) nos indivíduos com artrite reumatoide (AR) com resistência à insulina (RI) parece produzir mais melhoria na sensibilidade à insulina em pacientes com AR com peso normal do que em pacientes obesos com AR. Isso sugere que a inflamação sistêmica e a obesidade são fatores de risco independentes para a RI em pacientes com AR. Objetivos: Avaliar a resistência à insulina em pacientes com peso normal com AR (AR-PN), pacientes com sobrepeso com AR (AR-SP), pacientes com AR obesos (AR-OB) e indivíduos controle com peso normal (PN) e obesidade (OB) pareados; e a associação com as principais citocinas envolvidas na patogênese da doença. Métodos: As avaliações incluíram: índice de massa corporal (IMC), resistência à insulina com o modelo de avaliação da homeostase (Homa-IR), método Elisa e ensaio colorimétrico enzimático. Resultados: Os resultados marcantes do presente estudo incluíram: (1) Em pacientes com AR, a RI estava bem correlacionada com o Índice de Massa Corporal (quanto maior o IMC, maior a RI), mas não com os níveis séricos de citocinas. Na verdade, os níveis de citocinas eram semelhantes em todos os pacientes com AR, independentemente de serem obesos, com sobrepeso ou peso normal. (2) A RI foi significativamente maior no grupo AR-PN do que no grupo PN. (3) Não houve diferença estatisticamente significativa entre a RI de pacientes AR-OB e OB. (4) Como esperado, os níveis circulantes de citocinas foram significativamente maiores em pacientes com AR do que em OB. Conclusões: A obesidade parece ser uma condição mais importante do que a inflamação em produzir RI em pacientes com AR. A dissociação dos componentes da inflamação e da obesidade na produção de RI sugere a necessidade de uma estratégia terapêutica independente em pacientes obesos com AR.

Humans , Female , Adult , Arthritis, Rheumatoid/blood , Insulin Resistance/immunology , Tumor Necrosis Factor-alpha/blood , Obesity/blood , Arthritis, Rheumatoid/complications , Enzyme-Linked Immunosorbent Assay , Body Mass Index , Case-Control Studies , Interleukin-6/blood , Interleukin-1beta/blood , Middle Aged , Obesity/complications
Rev. bras. reumatol ; 57(4): 286-293, July.-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-899433


ABSTRACT Objectives: To evaluate the frequency of four serum biomarkers in RA patients and their relatives and identify possible associations with clinical findings of the disease. Methods: This was a transversal analytical study. Anti-cyclic citrullinated peptide (anti-CCP), anti-mutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in 210 RA patients, 198 relatives and 92 healthy controls from Southern Brazil. Clinical and demographic data were obtained through charts review and questionnaires. Results: A higher positivity for all antibodies was observed in RA patients when compared to relatives and controls (p < 0.0001). IgA-RF was more frequent in relatives compared to controls (14.6% vs. 5.4%, p = 0.03, OR = 2.98; 95% CI = 1.11-7.98) whereas anti-CCP was the most common biomarker among RA patients (75.6%). Concomitant positivity for the four biomarkers was more common in patients (46.2%, p < 0.0001). Relatives and controls were mostly positive for just one biomarker (20.2%, p < 0.0001 and 15.2%, p = 0.016, respectively). No association was observed between the number of positive biomarkers and age of disease onset, functional class or tobacco exposure. In seronegative patients predominate absence of extra articular manifestations (EAMs) (p = 0.01; OR = 3.25; 95% CI = 1.16-10.66). Arthralgia was present in positive relatives, regardless the type of biomarker. Conclusions: A higher number of biomarkers was present in RA patients with EAMs. Positivity of biomarkers was related to arthralgia in relatives. These findings reinforce the link between distinct biomarkers and the pathophysiologic mechanisms of AR.

RESUMO Objetivos: Avaliar a frequência de quatro marcadores sorológicos em pacientes com AR e seus familiares e identificar possíveis associações com achados clínicos da doença. Métodos: Estudo analítico transversal. Determinaram-se os níveis de anticorpos antipeptídeo citrulinado cíclico (anti-CCP), anticorpos antivimentina citrulinada-mutada (anti-MCV) e fator reumatoide (FR) IgA por Elisa e de FR-IgM por aglutinação em látex em 210 pacientes com AR, 198 familiares e 92 controles saudáveis do sul do Brasil. Coletaram-se dados clínicos e demográficos por meio da revisão de prontuários e questionários. Resultados: Observou-se maior positividade para todos os anticorpos em pacientes com AR em comparação com os familiares e controles (p < 0,0001). O FR-IgA era mais frequente em familiares quando comparados com os controles (14,6% versus 5,4%, p = 0,03, OR = 2,98; IC95% = 1,11 a 7,98). O anti-CCP foi o biomarcador mais comum entre pacientes com AR (75,6%). A positividade concomitante para os quatro biomarcadores foi mais comum nos pacientes (46,2%, p < 0,0001). Familiares e controles eram positivos em sua maioria para apenas um biomarcador (20,2%, p < 0,0001 e 15,2%, p = 0,016, respectivamente). Não foi observada associação entre o número de biomarcadores positivos e a idade de início da doença, classe funcional ou exposição ao fumo. Em pacientes soronegativos, predominou a ausência de manifestações extra-articulares (MEA) (p = 0,01; OR = 3,25; IC95% = 1,16 a 10,66). A artralgia estava presente em familiares positivos, independentemente do tipo de biomarcador. Conclusões: Um maior número de biomarcadores estava presente em pacientes com AR com MEA. A positividade dos biomarcadores estava relacionada com a artralgia em familiares. Esses achados reforçam a ligação entre os diferentes biomarcadores e os mecanismos fisiopatológicos da AR.

Humans , Male , Female , Adult , Arthritis, Rheumatoid/blood , Rheumatoid Factor/blood , Vimentin/blood , Anti-Citrullinated Protein Antibodies/blood , Arthritis, Rheumatoid/classification , Arthritis, Rheumatoid/complications , Enzyme-Linked Immunosorbent Assay , Biomarkers/blood , Case-Control Studies , Arthralgia/etiology , Middle Aged
Rev. bras. reumatol ; 57(3): 190-196, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-899423


ABSTRACT Objective: The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of patients with rheumatoid arthritis. Methods: Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+CD4+T, CD4+CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. Results: The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23 ± 10.71)% vs. (18.83 ± 7.32)%, p < 0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71 ± 1.63) vs. (2.00 ± 1.27), p = 0.002; (2.62 ± 2.08) vs. (0.62 ± 0.29), p < 0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90 (6.10 ± 80.10)% vs. (52.49 ± 19.18)%, p < 0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49 ± 19.18)% vs. (23.18 ± 5.62)% vs. (18.06 ± 7.80)%, X 2 = 24.03, p < 0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs [(46.02 ± 14.68)% vs. 17.90 (6.10 ± 80.10)% vs. (34.22 ± 10.33)%, X 2 = 38.29, p < 0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+CD25+T cells. Conclusion: AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.

RESUMO Objetivo: Analisar o papel do receptor de hidrocarboneto arílico (AhR) nos linfócitos T CCR6+ CD4+ e CD4+ CD25+ no sangue periférico de pacientes com artrite reumatoide (AR). Métodos: Foi aplicada citometria de fluxo para determinar a proporção de células AhR positivas em linfócitos CCR6+ CD4+ e CD4+ CD25+ do sangue periférico e células mononucleares periféricas de cada indivíduo. Os níveis de expressão relativa de ácido ribonucleico mensageiro (do inglês ribonucleic acid, RNAm,) de AhR e RNAm de enzima de primeiro estágio essencial para o AhR (CYP1A1) foram testados por reação em cadeia de polimerase (do inglês polymerase chain reaction, PCR,) em tempo real. Resultados: A percentagem de células AhR positivas nas células mononucleares do sangue periférico foi maior no grupo com AR do que nos indivíduos saudáveis [(35,23 ± 10,71)% vs. (18,83 ± 7,32)%, (p < 0,01)]. Os níveis de expressão de AhR e CYP1A1 estavam aumentados em pacientes com AR quando comparados com os controles [(3,71 ± 1,63) vs. (2,00 ± 1,27), p = 0,002; (2,62 ± 2,08) vs. (0,62 ± 0,29), p < 0,01, respectivamente]. Em pacientes com AR, a percentagem de células AhR positivas nos linfócitos T CD4+ CD25+ foi significativamente inferior à dos controles [17,90 (6,10 ± 80,10)]% vs. (52,49 ± 19,18)%, p < 0,01]; em controles saudáveis, a percentagem de células AhR positivas nos linfócitos T CD4+ CD25+ foi significativamente mais elevada do que nos linfócitos T CCR6+ CD4+ e também foi significativamente maior do que nas células mononucleares do sangue periférico (do inglês peripheral blood mononuclear cells, PBMC,) [(52,49 ± 19,18)% vs. (23,18 ± 5,62)% vs. (18,06 ± 7,80)%, X 2 = 24,03, p < 0,01]; em pacientes com AR, a percentagem de células AHR positivas nos linfócitos T CCR6+ CD4+ era significativamente maior em comparação com os linfócitos T CD4+ CD25+ e PBMC (46,02 ± 14,68)% vs. [17,90 (6,10 ± 80.10)]% vs. (34,22 ± 10,33)%, X2 = 38,29, p < 0,01]; no entanto, não foi encontrada correlação estatisticamente significativa entre os dados clínicos e células AhR positivas em linfócitos T CCR6+ CD4+ e CD4+ CD25+. Conclusão: O Ahr pode participar do progresso patológico da AR ao controlar a diferenciação de linfócitos Th17 e Treg no sangue periférico.

Humans , Female , Child , Arthritis, Rheumatoid/immunology , T-Lymphocytes/metabolism , Receptors, Aryl Hydrocarbon/blood , Basic Helix-Loop-Helix Transcription Factors/blood , Arthritis, Rheumatoid/blood , Biomarkers/blood , CD4-Positive T-Lymphocytes/metabolism , Case-Control Studies , T-Lymphocytes, Regulatory/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Interleukin-2 Receptor alpha Subunit/blood , Receptors, CCR6/blood , Th17 Cells/metabolism , Real-Time Polymerase Chain Reaction , Flow Cytometry , Middle Aged
Rev. bras. reumatol ; 57(3): 238-244, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-899413


ABSTRACT Objective: To evaluate the influence of periodontal treatment on rheumatoid arthritis activity. Methods: MEDLINE/PUBMED, The Cochrane Library, Clinical Trials, SciELO and LILACS were searched for studies published until December 2014. Included articles were: prospective studies; including patients older than 18 years, diagnosed with periodontitis and rheumatoid arthritis submitted to non-surgical periodontal treatment; with a control group receiving no periodontal treatment; with outcomes including at least one marker of rheumatoid arthritis activity. Methodological quality of the studies was assessed using PEDro scale. Quantitative data were pooled in statistical meta-analysis using Review Manager 5. Results: Four articles were included. Non-surgical periodontal treatment was associated with a significant reduction of DAS28 (OR: -1.18; 95% CI: -1.43, -0.93; p < 0.00001). Erythrocyte sedimentation rate, C-reactive protein, patient's assessment of rheumatoid activity using visual analogical scale, tender and swollen joint counts showed a trend toward reduction (not statistically significant). Conclusions: The reduction of DAS 28 in patients with rheumatoid arthritis after periodontal treatment suggests that the improvement of periodontal condition is beneficial to these patients. Further randomized controlled clinical trials are necessary to confirm this finding.

RESUMO Objetivo: Avaliar a influência do tratamento periodontal sobre a atividade da doença na artrite reumatoide. Métodos: Pesquisaram-se as bases de dados Medline/PubMed, The Cochrane Library, Clinical Trials, SciELO e Lilacs em busca de estudos publicados até dezembro de 2014. Incluíram-se estudos prospectivos que avaliaram pacientes com mais de 18 anos diagnosticados com periodontite e artrite reumatoide submetidos a tratamento periodontal não cirúrgico; os estudos deveriam ter também um grupo controle não submetido a tratamento periodontal. Os resultados dos estudos deveriam contar com pelo menos um marcador da atividade da doença na artrite reumatoide. A qualidade metodológica dos estudos foi avaliada com a escala PEDro. Reuniram-se os dados quantitativos em uma metanálise estatística com o uso do Review Manager 5. Resultados: Incluíram-se quatro artigos. O tratamento periodontal não cirúrgico esteve associado a uma redução significativa no DAS-28 (OR: -1,18; IC 95%: -1,43 a -0,93; p < 0,00001). A velocidade de hemossedimentação, a proteína C-reativa, a avaliação da atividade reumatoide pela escala visual analógica e as contagens de articulações sensíveis e inchadas apresentaram uma tendência de redução (não estatisticamente significativa). Conclusões: A redução no DAS-28 em pacientes com artrite reumatoide após tratamento periodontal sugere que a melhoria na condição periodontal é benéfica a esses pacientes. São necessários mais ensaios clínicos randomizados controlados para confirmar esse achado.

Humans , Periodontal Diseases/therapy , Arthritis, Rheumatoid/complications , Periodontal Diseases/etiology , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/blood , Severity of Illness Index , Biomarkers/blood , Treatment Outcome
Rev. bras. reumatol ; 57(1): 15-22, Jan.-Feb. 2017. tab
Article in English | LILACS | ID: biblio-844209


ABSTRACT Introduction: The presence of anti-CCP is an important prognostic tool of rheumatoid arthritis (RA). But research is still ongoing on its relationship with disease activity and functional capacity. Objectives: To study the relationship between anti-CCP and disease activity, functional capacity and structural damage indexes, by means of conventional radiography (CR) and magnetic resonance imaging (MRI), in cases of established RA. Methods: Cross-sectional study with RA patients with 1–10 disease duration. Participants underwent clinical evaluation with anti-CCP. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and functional capacity through the Health Assessment Questionnaire (HAQ). CR analysis was carried out by the Sharp van der Heijde index (SvdH), and MRI analysis by RAMRIS (Rheumatoid Arthritis Magnetic Resonance Image Scoring). Results: We evaluated 56 patients, with a median (IqR) age of 55 (47.5–60) years; 50 (89.3%) participants were female and 37 (66.1%) were positive for anti-CCP. Medians (IqR) of CDAI, HAQ, SvdH and RAMRIS were 14.75 (5.42–24.97) 1.06 (0.28–1.75), 2 (0–8) and 15 (7–35), respectively. There was no association between anti-CCP and CDAI, HAQ and SvdH and RAMRIS scores. Conclusion: Our results have not established an association of anti-CCP with the severity of disease. To date, we cannot corroborate anti-CCP as a prognostic tool in patients with established RA.

RESUMO Introdução: A presença do anti-CCP constitui importante ferramenta prognóstica da artrite reumatoide (AR), mas ainda se investiga sua relação com a atividade da doença e a a capacidade funcional. Objetivos: Estudar a relação do anti-CCP com os índices de atividade da doença, de capacidade funcional e de dano estrutural, por meio de radiografia convencional (RC) e de ressonância magnética (RM), em AR estabelecida. Métodos: Estudo transversal com pacientes com AR, com um a 10 anos de doença. Os participantes foram submetidos à avaliação clínica com pesquisa do anti-CCP. A atividade de doença foi avaliada por meio do Clinical Disease Activity Index (CDAI) e a capacidade funcional por meio do Health Assessment Questionnaire (HAQ). A análise da RC foi feita pelo índice de Sharp van der Heijde (SmvH) e da RM pelo Sistema de Pontuação de Imagem por Ressonância Magnética na Artrite Reumatoide (RAMRIS, Rheumatoid Arthritis Magnetic Resonance Image Scoring). Resultados: Foram avaliados 56 pacientes, com mediana (IIq) de 55 (47,5-60,0) anos, 50 (89,3%) do sexo feminino e 37 (66,1%) anti-CCP positivos. As medianas (IIq) do CDAI, do HAQ, de SmvH e do RAMRIS foram de 14,75 (5,42-24,97), 1,06 (0,28-1,75), 2 (0-8) e 15 (7-35), respectivamente. Não houve associação do anti-CCP com o CDAI, com o HAQ e com os escores SmvH e RAMRIS. Conclusão: Nossos resultados não estabeleceram a associação do anti-CCP com a gravidade da doença. Até o momento, não podemos corroborar o anti-CCP como uma ferramenta prognóstica em AR estabelecida.

Humans , Male , Peptides, Cyclic/immunology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/diagnostic imaging , Autoantibodies/immunology , Magnetic Resonance Imaging , Peptides, Cyclic/blood , Arthritis, Rheumatoid/physiopathology , Arthritis, Rheumatoid/blood , Prognosis , Rheumatoid Factor/blood , Autoantibodies/blood , Severity of Illness Index , Biomarkers/blood , Cross-Sectional Studies , Predictive Value of Tests , Middle Aged
Rev. bras. reumatol ; 56(5): 451-457, Sept.-Oct. 2016. tab
Article in English | LILACS | ID: lil-798098


ABSTRACT A better understanding of the inflammatory mechanisms of rheumatoid arthritis and the development of biological therapy revolutionized its treatment, enabling an interference in the synovitis – structural damage – functional disability cycle. Interleukin 33 was recently described as a new member of the interleukin-1 family, whose common feature is its pro-inflammatory activity. Its involvement in the pathogenesis of a variety of diseases, including autoimmune diseases, raises the interest in the possible relationship with rheumatoid arthritis. Its action has been evaluated in experimental models of arthritis as well as in serum, synovial fluid and membrane of patients with rheumatoid arthritis. It has been shown that the administration of interleukin-33 exacerbates collagen-induced arthritis in experimental models, and a positive correlation between cytokine concentrations in serum and synovial fluid of patients with rheumatoid arthritis and disease activity was found. This review discusses evidence for the role of interleukin-33 with a focus on rheumatoid arthritis.

RESUMO A melhor compreensão dos mecanismos inflamatórios da artrite reumatoide e o desenvolvimento da terapia biológica revolucionaram o tratamento da doença, permitindo uma interferência no ciclo sinovite–dano estrutural–incapacidade funcional. A interleucina 33 foi recentemente descrita como um novo membro da família da interleucina 1, cuja característica comum é a atividade pró-inflamatória. Por estar envolvida na patogênese de uma grande variedade de doenças, incluindo doenças autoimunes, a interleucina 33 começa a ser estudada na doença reumatoide. Ela tem sido avaliada em modelos experimentais de artrite, no soro, no líquido e membrana sinoviais de pacientes com artrite reumatoide. Demonstrou-se que a administração da interleucina 33 exacerba a artrite induzida por colágeno em modelos experimentais, e concentrações dessa citocina no soro e no líquido sinovial de pacientes com artrite reumatoide correlacionaram-se positivamente com a atividade da doença. Esse manuscrito apresenta a interleucina 33 e discute as evidências do seu papel em diferentes doenças, com ênfase na artrite reumatoide.

Humans , Animals , Arthritis, Experimental/immunology , Arthritis, Rheumatoid/pathology , Interleukin-33/immunology , Interleukin-33/blood , Arthritis, Experimental/pathology , Arthritis, Experimental/blood , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Synovial Fluid , Synovitis , Interleukins
Rev. bras. reumatol ; 56(4): 287-298, July-Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-792760


ABSTRACT Introduction: Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue characterized by the triad of vascular injury, autoimmunity (cellular and humoral) and tissue fibrosis. It is estimated that musculoskeletal pain is a common complaint of patients with SSc, ranging from 40 to 80%, and mainly in patients with early diffuse disease. Arthritis, clinically observed, may be a feature seen in the presentation of SSc, often leading to early diagnostic errors with rheumatoid arthritis (RA). In the course of the disease, arthritis is observed in 24–97% of patients with SSc. Objectives: To correlate the occurrence or nonoccurrence of arthritis in patients with SSc of the Midwest region of Brazil with possible distinct clinical and laboratory manifestations observed in three groups of patients. To report the frequency of true association between systemic sclerosis and rheumatoid arthritis in patients with clinically and radiologically observed synovitis. Methods: Sixty-one SSc patients were subsequently assessed every 3 months within 1 year, in order to clinically observe the occurrence of synovitis and its patterns of progression. Patients were divided into 3 groups: 41 patients with SSc without arthritis, 16 SSc patients with arthritis and 4 patients with overlap of SSc and RA. All patients underwent a radiological examination of the hands at the end of the study. Results: Among all patients evaluated, we found a female predominance (98.7%), mean age of 50.94 years, white color (49.2%), limited form of the disease (47.6%), time of diagnosis between 5 and 10 years (47.6%) and duration of the disease of 8.30 years. Among all patients, 14 (22.9%) had positive rheumatoid factor (RF), while among those with positive RF, only 10 patients had arthritis during one-year follow-up. The antibody anticitrulline (anti-CCP) test was performed in 24 patients, being positive in 4 of them (16.7%), with positivity being observed only in patients with SSc/RA overlap. Comparing the clinical manifestations among the groups of patients, there was a higher incidence of gastritis and cardiac valvulopathy in patients with SSc and arthritis, but not in the others. In the group of patients with SSc/RA overlap and in patients with SSc and arthritis a significant reduction in quality of life was observed, measured by HAQ index, especially in patients with arthritis present during clinical evaluation. We found radiographic changes in 42.6% of patients with SSc. However, in patients with synovitis, radiological changes consistent with rheumatoid arthritis were found in 50% of patients. Conclusions: While the frequency of clinical arthritis observed in patients with systemic sclerosis was 32.8%, the true overlap between of SSc and RA was 6.6% in this study. We also observed the frequency of positive anti-CCP in 20% of patients with arthritis versus no patients with SSc without arthritis.

RESUMO Introdução: A esclerose sistêmica (ES) é uma enfermidade do tecido conjuntivo de caráter autoimune caracterizada pela tríade de injúria vascular, autoimunidade (celular e humoral) e fibrose tecidual. Estima-se que a dor musculoesquelética seja uma queixa frequente dos pacientes com ES, que oscila entre 40% e 80%, e principalmente em pacientes com doença difusa precoce. A artrite, clinicamente observada, pode ser uma característica observada na apresentação da ES, frequentemente leva a erros diagnósticos iniciais com artrite reumatoide (AR). No curso da enfermidade, a artrite é observada em 24% a 97% dos pacientes com ES. Objetivos: Correlacionar a ocorrência ou não de artrite em pacientes com ES da região Centro-Oeste do Brasil com possíveis manifestações clínicas e laboratoriais distintas observadas em três grupos de pacientes. Relatar a frequência de verdadeira associação entre esclerose sistêmica e artrite reumatoide em pacientes com sinovite clínica e radiologicamente observada. Métodos: Foram avaliados 61 pacientes portadores de ES subsequentemente a cada três meses durante um ano, para fins de se constatar clinicamente a ocorrência de sinovite e padrões de evolução. Os pacientes foram divididos em três grupos: 41 com ES sem artrite, 16 com ES com artrite e quatro com sobreposição entre ES e AR. Todos os pacientes foram submetidos a exame radiológicos das mãos no fim do estudo. Resultados: Dentre todos os pacientes avaliados, encontrou-se predomínio feminino (98,7%), idade média de 50,94 anos, cor branca (49,2%), forma limitada da doença (47,6%), tempo de diagnóstico entre cinco e 10 anos (47,6%) e tempo de evolução da doença de 8,30 anos. Entre todos os pacientes, 14 (22,9%) apresentavam fator reumatoide (FR) positivo, embora entre aqueles com FR positivo apenas 10 apresentaram artrite durante o seguimento de um ano. O anticorpo anticitrulina (anti- CCP) foi feito em 24 pacientes, com positividade em quatro deles (16,7%), observada somente nos pacientes com sobreposição ES/AR. Na comparação das manifestações clínicas entre os grupos de pacientes, observou-se a maior ocorrência de gastrite e valvulopatia cardíaca em pacientes com ES e artrite, mas não nos demais grupos. No grupo de pacientes com overlap ES/AR e nos pacientes com ES e artrite observou-se redução importante de qualidade de vida, medida pelo índice HAQ, sobretudo nos pacientes com artrite presente no momento da avaliação clínica. Encontramos alterações radiográficas em 42,6% dos pacientes com ES. Contudo, nos pacientes com sinovite, encontraram-se alterações radiológicas compatíveis com artrite reumatoide em 50%. Conclusões: Enquanto a frequência de artrite clínica observada em pacientes com esclerose sistêmica foi de 32,8%, a verdadeira sobreposição entre ES e AR foi de 6,6% neste estudo. Observou-se ainda a frequência de anti-CCP positivo em 20% dos pacientes com artrite contra nenhum paciente com ES sem artrite.

Humans , Female , Arthritis, Rheumatoid/complications , Scleroderma, Systemic/complications , Anti-Citrullinated Protein Antibodies/blood , Peptides, Cyclic/blood , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Quality of Life , Scleroderma, Systemic/immunology , Scleroderma, Systemic/blood , Autoantibodies/blood , Brazil , Comorbidity
Rev. bras. reumatol ; 55(6): 485-492, nov.-dez. 2015. tab
Article in English | LILACS | ID: lil-770017


Resumo Introdução: Relata-se que o polimorfismo do gene timidilato sintase (TS) e a homocisteína têm relação com o metabolismo do metotrexato (MTX), com achados conflitantes. O objetivo deste estudo foi determinar os níveis de homocisteína e a frequência de polimorfismos de repetição tripla (TS3R) e dupla (TS2R) do gene TS em um grupo de pacientes turcos com AR e avaliar sua associação com a toxicidade ao MTX e a atividade da doença. Métodos: Foram incluídos no estudo 64 pacientes com AR e 31 indivíduos no grupo controle, com média de 48,7 ± 12,5 e 46,2 ± 13,4 anos. Foram obtidas as características demográficas e foi registrado o número de pacientes que relataram efeitos adversos ao MTX no grupo AR. Foram analisados os níveis de homocisteína e os polimorfismos TS2R/TS3R. Foi determinada a distribuição de genótipos de acordo com a toxicidade ao MTX e a atividade da doença. Resultados: Os dados demográficos foram semelhantes entre os pacientes e controles. Todos faziam suplementação de ácido fólico a uma dose média de 5 mg/semana. Dos 64 pacientes, 36 apresentaram efeitos adversos ao tratamento com MTX. Encontrou-se uma frequência de polimorfismos TS2R e TS3R semelhante nos grupos AR e controle. Encontrou-se que os polimorfismos TS2R e TS3R eram semelhantes em pacientes com e sem eventos adversos relacionados com o MTX. O nível médio de homocisteína também foi similar em pacientes com e sem polimorfismo do gene TS, mas era mais elevado (12,45 μmol/L vs. 10,7 μmol/L) em pacientes com do que sem efeitos adversos relacionados com o MTX. O nível médio de homocisteína se correlacionou com o VHS no grupo AR. Conclusões: Os níveis de homocisteína podem afetar a atividade da doença e a toxicidade ao MTX, mas os polimorfismos 2 R e 3 R no gene TS não se correlacionaram com a toxicidade ao MTX em pacientes com AR que recebem suplementação de ácido fólico. São necessários mais estudos para esclarecer os polimorfismos em outras enzimas que podem ser responsáveis pela toxicidade ao MTX em pacientes com AR.

Abstract Background: The polymorphism of thymidylate synthase (TS) gene and homocysteine are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine homocysteine levels and the frequency of TS gene triple repeat (TS3R) and double repeat (TS2R) polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity and disease activity. Methods: Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ± 12.5 and 46.2 ± 13.4 years were enrolled for the study. Demographic characteristics were obtained and a number of patients with MTX-related adverse affects were recorded in the patient group. The homocysteine levels and TS2R/TS3R polymorphisms of the TS gene were analyzed and the distribution of genotypes according to MTX toxicity and disease activity was determined. Results: The demographic properties were similar between the patient and control subjects. Folic acid supplementation with a mean dose of 5 mg folic acid/week was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment. The respective frequency of TS2R and TS3R polymorphisms was found to be similar in the patient and control groups. TS2R and TS3R gene polymorphisms were found to be similar in patients with and without MTX-related adverse events. The mean homocysteine level was also similar in patients with and without TS gene polymorphism, but was found to be higher (12.45 μmol/L vs 10.7 μmol/L) in patients with MTX-related side effects than in patients without side effects. The mean level of homocysteine was correlated with levels of ESR in the patient group. Conclusions: In conclusion, homocysteine levels might affect the disease activity and toxicity of MTX but 2R and 3R polymorphisms in the TS gene were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible for the MTX toxicity in patients suffering from RA.

Humans , Male , Female , Adult , Polymorphism, Genetic , Arthritis, Rheumatoid/enzymology , Arthritis, Rheumatoid/blood , Thymidylate Synthase/genetics , Methotrexate/adverse effects , Antirheumatic Agents/adverse effects , Homocysteine/blood , Arthritis, Rheumatoid/drug therapy , Vitamin B Complex/administration & dosage , Case-Control Studies , Methotrexate/metabolism , Antirheumatic Agents/metabolism , Folic Acid/administration & dosage , Middle Aged
Rev. bras. reumatol ; 55(6): 493-500, nov.-dez. 2015. tab
Article in English | LILACS | ID: lil-770019


Resumo Objetivo: Caracterizar pacientes com artrite reumatoide (AR) quanto à presença de fatores de risco para doenças cardiovasculares. Material e métodos: Estudo transversal descritivo com 71 pacientes diagnosticados com AR definida. Foram usados os instrumentos: DAS-28, HAQ e SF-36 e determinados os parâmetros: velocidade de hemossedimentação, glicemia capilar, colesterol total (CT) e suas frações, hormônios tiroidianos, anticorpos antinúcleo (ANA), fator reumatoide (FR) e anticorpos contra proteínas citrulinadas (ACPAs). Os pacientes foram classificados em grupos HAQ ≤ 1 (disfunção leve) e HAQ > 1 (disfunção moderada e grave) e, segundo os escores do HAQ, em grupo tratado com corticosteroides (CE) e sem CE. Resultados: Proporção de nove homens para 62 mulheres com idade e tempo médio de doença de 53,45 (± 10,7) e 9,9 (± 8,6), respectivamente. O FR foi positivo em 52 (76%), os ACPAs em 54 (76,1%) e o ANA em 12 (16,9%). Trinta e seis pacientes (50,7%) apresentaram hipertensão arterial sistêmica, nove (12,68%) diabetes mellitus, 16 (22,5%) hipotireoidismo, 33 (46,5%) dislipidemia e oito (11,27%) tabagismo. O grupo HAQ > 1 (26) apresentou resultados de CT > 240 (53,8%) e o grupo com HAQ ≤ 1 (45) (24,4%) (p = 0,020). Os grupos não diferiram quanto à presença de comorbidades ou tratamento farmacológico. Os níveis de triglicérides > 200 (42,4%) entre os grupos em uso de CE e sem uso (18,42%) foi significativo (p = 0,025). Conclusão: Houve associação do aumento CT e triglicerídeos com resultados de HAQ ≤ 1 e com uso de CE, o que reforça a importância do rastreamento de fatores de risco associados às doenças cardiovasculares na AR.

Abstract Objective: To identify risk factors for cardiovascular disease in patients with Rheumatoid Arthritis (RA). Material and methods: A descriptive cross-sectional study with 71 patients with established RA. The instruments used were: DAS-28, HAQ and SF-36, and the following parameters were determined: the erythrocyte sedimentation rate, capillary blood glucose; total cholesterol (TC) and its fractions, thyroid hormones, antinuclear antibodies (ANA), rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPAs). Patients were classified into groups HAQ ≤ 1 (mild dysfunction) and HAQ > 1 (moderate and severe dysfunction) and, according to the HAQ scores, in groups treated with corticosteroids (CS) and without CS. Results: 9 patients were male and 62 female with mean age and duration of disease of 53.45 (±10.7) and 9.9 (±8.6), respectively. RF was positive in 52 (76%), ACPAs in 54 (76.1%) and ANA in 12 (16.9%). Thirty-six patients (50.7%) had systemic hypertension, 9 (12.68%) diabetes mellitus, 16 (22.5%) hypothyroidism, 33 (46.5%) dyslipidemia and 8 (11.27%) were smokers. The results of TC > 240 were found in 53.8% for group HAQ > 1 (26) and in 24.4% for group HAQ ≤ 1 (45) (p = 0.020). These groups did not differ as to presence of comorbidities or drug treatment. Triglyceride levels >200 for the group with CS (42.4%) versus without CS (18.42%) were significant (p = 0.025). Conclusion: An association of increased TC and triglycerides with results of HAQ ≤ 1 and with CS use was noted, reinforcing the importance of screening risk factors associated with cardiovascular disease in RA.

Humans , Male , Female , Arthritis, Rheumatoid/complications , Cardiovascular Diseases/etiology , Arthritis, Rheumatoid/blood , Rheumatoid Factor/blood , Blood Glucose/analysis , Blood Sedimentation , Brazil , Cardiovascular Diseases/blood , Cholesterol/blood , Cross-Sectional Studies , Risk Factors , Anti-Citrullinated Protein Antibodies/blood , Middle Aged
Clinics ; 70(11): 738-742, Nov. 2015. tab
Article in English | LILACS | ID: lil-766147


OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all p<0.05). RANKL expression was higher in MG63 cells treated with serum from patients with ankylosing spondylitis or rheumatoid arthritis than in those treated with serum from controls (both p<0.05). The OPG/RANKL ratio was also higher in MG63 cells treated with serum from ankylosing spondylitis patients than in those treated with serum from controls (p<0.05). No associations were found between the expression of the five genes and the patient demographics and clinical assessments (all p>0.05). CONCLUSIONS : Serum from ankylosing spondylitis patients increases PPARD, fra-1, MMP7, OPG and RANKL expression and the OPG/RANKL ratio in MG63 cells; these effects may be due to the stimulatory effect of the serum on the Wnt pathway.

Adult , Female , Humans , Male , Middle Aged , Young Adult , Arthritis, Rheumatoid/blood , Osteoblasts/metabolism , Serum , Spondylitis, Ankylosing/blood , Cells, Cultured , Culture Media , Cytokines/metabolism , Gene Expression , /metabolism , PPAR delta/metabolism , Proto-Oncogene Proteins c-fos/metabolism , RANK Ligand/metabolism , Real-Time Polymerase Chain Reaction , Wnt Signaling Pathway/genetics , beta Catenin/genetics
Yonsei Medical Journal ; : 1134-1142, 2015.
Article in English | WPRIM | ID: wpr-150468


PURPOSE: Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Chemokines are involved in RA pathogenesis. In this study, we investigated the chemokine signaling pathway associated with CCL2 in peripheral blood (PB) and synovial tissues (ST) of RA patients based on our previous work about chemokine signaling pathway involved in the activation of CCL2 production in collagen-induced arthritis rat ST. MATERIALS AND METHODS: Total RNA was isolated from PB leukocytes and synovium of the knee joint in both RA patients and control populations. Real-time polymerase chain reaction was used to determine CCL4, CCR5, c-Jun, c-Fos, and CCL2 expressions. Serum level of CCL2 was assessed by enzyme-linked immunosorbent assay, and the production of CCL2 in ST was analyzed immunohistochemically. RESULTS: The expressions of CCL4, CCR5, c-Jun, c-Fos, and CCL2 messenger RNA in RA patients were significantly higher than those in healthy controls, both in ST and on PB leukocyte. Serum CCL2 levels were elevated in RA patients. Histological examination of rheumatoid joints revealed extensive CCL2 expression in RA ST. CONCLUSION: CCL2, CCL4, c-Jun, c-Fos, and CCR5 may play an important role in the recruitment of PB leukocytes into the RA joints. These data provide evidence that the chemokine signaling pathway is involved in CCL2 expression in RA patient tissues, which may contribute to chronic inflammation associated with RA. Targeting this signaling pathway may provide a novel therapeutic avenue in RA.

Adult , Animals , Arthritis, Rheumatoid/blood , Case-Control Studies , Chemokine CCL2/blood , Chemokines/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression , Humans , Male , Middle Aged , RNA, Messenger/genetics , Rats , Real-Time Polymerase Chain Reaction , Signal Transduction , Synovial Membrane/metabolism
Rev. bras. reumatol ; 54(6): 446-451, Nov-Dec/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-731268


Introdução O estresse oxidativo produzido no interior de articulações inflamadas pode produzir fenômenos autoimunes e destruição articular. As espécies radicais com atividade oxidativa, incluindo espécies reativas de nitrogênio, representam mediadores de inflamação e de lesão cartilaginosa. Objetivos Avaliar o óxido nítrico sérico como marcador de estresse oxidativo em pacientes egípcios com artrite reumatoide e sua relação com a atividade da doença. Métodos 80 com artrite reumatoide foram divididos em dois grupos, de acordo com a pontuação DAS28: Grupo I: 42 pacientes com doença ativa, e Grupo II: 38 pacientes com doença inativa. Quarenta indivíduos equiparados por idade e gênero foram incluídos como grupo controle (Grupo III). Foram realizados exames laboratoriais de rotina e o óxido nítrico foi medido usando Elisa. Radiografias simples das mãos foram feitas para a pontuação do estado radiológico utilizando o método de Sharpe. Resultados A comparação do nível sérico de óxido nítrico entre os três grupos mostrou uma diferença altamente significativa (p < 0,001). Obtiveram-se níveis significativamente mais elevados entre os pacientes com artrite reumatoide em comparação com os controles. Os níveis mais elevados foram obtidos em pacientes com a doença ativa (média±DP 82,38±20,46) em comparação com aqueles com a doença inativa (35,53±7,15). O óxido nítrico no Grupo I exibiu uma correlação positiva significativa com a rigidez matinal (r=0,45), artrite (r=0,43), contagem de plaquetas (r=0,46), velocidade de hemossedimentação (r=0,83), proteína C-reativa (r=0,76) e Índice de Atividade de Doença (r=0,85). O óxido ...

Background Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage. Objectives To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity. Methods Eighty patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method. Results A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I. Conclusion There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status. .

Humans , Male , Female , Adult , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/blood , Nitric Oxide/blood , Biomarkers/blood , Cross-Sectional Studies , Egypt , Middle Aged
Rev. bras. reumatol ; 54(6): 437-440, Nov-Dec/2014. tab
Article in Portuguese | LILACS | ID: lil-731274


Objetivos Este estudo tem como objetivo investigar a relação entre o nível de hemoglobina e a atividade da doença em pacientes com artrite reumatoide (AR). Pacientes e métodos Avaliou-se a possível relação existente entre o nível de hemoglobina, a contagem de 66/68 articulações, o Escore de Atividade da Doença – 28 articulações (DAS28), o Questionário de Avaliação de Saúde (HAQ), a escala visual analógica (EVA), o Escore de Sharp modificado (MSS) e a duração da doença de 89 pacientes com AR. Os critérios para anemia da Organização Mundial de Saúde (OMS) consideram um limite de hemoglobina<120g/L para as mulheres e<130g/L para os homens. Pacientes grávidas ou amamentando, pacientes com história de outra artrite inflamatória ou não inflamatória, neoplasias, doenças crônicas infecciosas e inflamatórias e outras doenças descompensadas foram excluídas do estudo. Resultados A anemia foi observada em 64% dos pacientes (1° grupo); o outro grupo (2° grupo) apresentou níveis normais de hemoglobina. Houve uma correlação negativa estatisticamente significativa entre o nível de hemoglobina e a contagem de articulações inchadas e sensíveis, DAS28, HAQ, EVA, MSS e duração da doença (p<0,001). O DAS28, escore HAQ, EVA, MSS, contagem de articulações inchadas e sensíveis e duração da doença foram significativamente maiores (p<0,001) no primeiro grupo em comparação com o segundo. Conclusão Determinou-se que o baixo nível de hemoglobina está significativamente correlacionado com a deficiência e incapacidade, atividade da doença, lesão articular, dor e duração da doença em pacientes com AR. Acredita-se que, mantendo ...

Objectives This study aims to investigate the relationship of hemoglobin level with disease activity in patients with rheumatoid arthritis (RA). Patients and methods The hemoglobin level, the 66/68 joint count, the Disease Activity Score 28 joints (DAS28), the Health Assessment Questionnaire (HAQ), the Visual Analog Scales (VAS), the Modified Sharp Score (MSS), and the disease duration in 89 patients with RA were used to analyze the possible relationship. The World Health Organization (WHO) criteria for anemia uses a hemoglobin threshold of<120g/L for women and<130g/L for men. Pregnant or breastfeeding patients, patients with a history of other inflammatory or no inflammatory arthritis, malignancies, chronic infectious and inflammatory diseases and other diseases in the stage of decompensation were excluded from the study. Results Anemia was observed in 64% of the patients (1st group); the other group (2nd group) had normal levels of hemoglobin. There was a statistically significant negative correlation between hemoglobin level and swollen and tender joints’ count, DAS28, HAQ score, VAS, MSS, and disease duration (p<0.001). DAS28, HAQ score, VAS, MSS, swollen and tender joints’ count and disease duration were significantly (p<0.001) higher in 1st versus 2nd group. Conclusion In conclusion, we determined that low hemoglobin level was significantly related to disability and impairment, disease activity, articular damage, pain and disease duration in RA patients in our study. We believe that by keeping disease activity under control, therefore preventing articular damage, the disability in RA patients can be lessened or possibly even eliminated. .

Humans , Female , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/blood , Hemoglobins/analysis , Arthritis, Rheumatoid/complications , Severity of Illness Index , Middle Aged
Rev. bras. reumatol ; 54(1): 21-26, Jan-Feb/2014. tab
Article in Portuguese | LILACS | ID: lil-704291


Objetivo: Determinar a frequência de anticorpos antiparvovírus B19 (B19) em pacientes com artrite reumatoide (AR) e lúpus eritematoso sistêmico (LES), e a possível correlação da soropositividade anti-B19 com a atividade das doenças e a qualidade de vida. Pacientes e métodos: Foram utilizadas amostras séricas de 57 pacientes com AR, 45 com LES e 65 controles sadios. Empregou-se protocolo com dados clínicos, os índices Disease Activity Score 28 (DAS 28), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) e Health Assessment Questionnaire (HAQ). Realizou-se a sorologia anti-B19 por ensaio imunoenzimático (ELISA). Resultados: A média de idade dos pacientes foi de 42,74 14,09 anos, e a dos controles foi de 38,38 13,42 anos.Tinham doença ativa 79 (77,5%) pacientes, e doença inativa 23 (22,5%).Anti-B19 (IgG) foi reagente em 49 (86,0%) IC 95% (77,0 - 95,0)% pacientes com AR, em 38 (84,4%) IC 95% (73,9 - 95,0)% com LES e em 40 (61,5%) IC 95% (49,7 - 73,4)% controles (p = 0,002). Anti-B19 (IgM) foi reagente em 3 (5,3%) IC 95% (0,0 - 11,1)% pacientes com AR, em 7 (15,6%) IC 95% (5,0 - 26,2)% pacientes com LES e em 1 (1,5%) IC 95% (0,0 - 4,5)% controle (p = 0,011). Não houve correlação da reatividade anti-B19 com a atividade das doenças, os índices DAS 28, SLEDAI e HAQ. Conclusão: O presente estudo demonstrou que a população avaliada está exposta à infecção pelo B19, o que demanda atenção com suas manifestações, principalmente entre os pacientes que apresentam maior risco, como os imunossuprimidos. .

Objective: To determine the frequency of antiparvovírus B19 (B19) antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and the possible correlation of anti-B19 seropositivity with disease activity and quality of life. Patients and methods: Serum samples from 57 patients with RA, 45 with SLE and 65 healthy controls were used. We applied protocol with clinical data, and the Disease Activity Score 28 (DAS 28), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Health Assessment Questionnaire (HAQ) indexes. The anti-B19 serology was done by enzyme-linked immunosorbent assay (ELISA). Results: The mean age of patients was 42.74 ± 14.09 years, and of controls was 38.38 ± 13.42 years. 79 patients had active disease (77.5%), and 23 had inactive disease (22.5%). Anti-B19 (IgG) was positive in 49 (86.0%; CI 95% 77.0 - 95.0) RA patients, 38 (84.4%; CI 95% 73.9 - 95.0) SLE patients, and 40 (61.5%; CI 95% 49.7 - 73.4) controls (p = 0.002). Anti-B19 (IgM) was positive in 3 (5.3%; CI 95% 0.0 - 11.1) RA patients, in 7 (15.6%; CI 95% 5.0 - 26,2) SLE patients, and in 1 (1.5%; CI 95% 0.0 - 4.5) control (p = 0.011).There was no correlation of anti-B19 reactivity with disease activity and with DAS 28, HAQ and SLEDAI indexes. Conclusion: This study demonstrated that the studied population is exposed to infection by B19, which demands attention with its manifestations, especially among patients at greatest risk, such as those immunosuppressed. .

Adolescent , Adult , Aged , Humans , Middle Aged , Young Adult , Antibodies, Viral/blood , Arthritis, Rheumatoid/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Lupus Erythematosus, Systemic/blood , /immunology