Association of New Generation Anti-CCP Antibodies with Disease Severity and Functional Status in Rheumatoid Arthritis Patients

@#Introduction: Detection of anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with rheumatoid arthritis (RA) is associated with higher disease activity and lower functional ability. This study investigated the presence of the new generation of anti-CCP antibodies (anti-CCP2 IgG, anti-CCP2 IgA and anti-CCP3.1 IgG/IgA) and their association with disease severity and functional status of RA patients. Methods: A total of 46 RA patients and 40 healthy controls participated in this cross-sectional study that was conducted at the Rheumatology Clinic, Hospital Universiti Sains Malaysia. Blood samples were taken from all participants for anti-CCP2 IgG, anti-CCP2 IgA, and anti-CCP3.1 IgG/IgA analysis. Disease severity and functional status of RA patients were measured using the Disease Activity Score-28 (DAS28) and the modified Health Assessment Questionnaire (mHAQ) respectively. Results: Significantly higher proportion of RA patients were found with positive anti-CCP2 IgG (63.0%), anti-CCP2 IgA (37.0%), and anti-CCP3.1 IgG/IgA antibodies (63.0%) than the healthy controls. No significant association was found between anti-CCP antibodies status and mean DAS28 score of the RA patients. However, RA patients with negative anti-CCP2 IgG status had higher mean mHAQ score than patients with positive anti-CCP2 IgG status. Conclusion: Our study has demonstrated detection of the new generation anti-CCP antibodies in RA patients, supporting the use of autoantibodies in RA diagnosis. While no significant association was found between the presence of anti-CCP antibodies and disease severity of RA patients, the absence of anti-CCP2 IgG was associated with worse function and greater disability of the patients.

Risk factors for the prognosis of rheumatoid arthritis-associated interstitial lung disease: a multicenter retrospective clinical study / 中华风湿病学杂志

Objective:To explore the impact of clinical features, serological indicators, and pulmonary function test (PFT) on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods:Clinical data of RA-ILD patients who were diagnosed by HRCT and were followed up in Changhai Hospital or Yancheng First People's Hospital from 2011 to 2021 were collected Respiratory functional impairment of the patients was evaluated according to the changes of HRCT score and PFT, and the patients were divided into progressive group and stable group. COX survival analysis and ROC curve were used to determine the factors related to the progression of RA-ILD.Results:Finally 98 RA-ILD patients were included. The mean age of ILD onset was (62.9±12.1) years old, the median course of RA was 7.0 (1.0, 15.3)years, and the median follow-up time was 36.5 months (14.0, 79.5). There were 49 cases in the progressive group, and the clinical characteristics and laboratory tests of the two groups were compared. The results showed that: progressive time [(23(8.5,43.0)months vs 63(32.5,90.9) months, Z=-4.55, P=0.001)], HRCT score [(115(109,135) vs 111(105,116), Z=-2.70, P=0.007)], forced vital capacity(FVC) predicted [(70.1±15.7)% vs (80.8±19.7)%, t=2.12, P=0.039)], diffusing capacity of the lungs for CO(DLCO) predicted [(57.5±16.3)% vs (83.4±18.8)%, t=4.87, P=0.001)], male [(44.9% vs 18.4%, χ2=7.97, P=0.005)], UIP pattern [(36(73.5%) vs 9(18.4%), χ2=29.96, P<0.001)], RF>200 U/ml[(21(65.6%) vs 18(41.9%), χ2=4.15, P=0.042)], anti-CCP>75 U/ml [(42(91.3%) vs 35(71.4%), χ2=6.10, P=0.013], all had significantly different between the two groups. In multivariate analyses, UIP[ HR(95% CI)=3.25(1.62,6.50), P<0.001], anti-CCP antibody >75 U/ ml[ HR(95% CI)=3.85 (1.20,12.33), P=0.023] and smoking [ HR (95% CI): 5.74(1.10, 30.13), P=0.039] were significantly correlated with the progression of pulmonary fibrosis in RA-ILD patients. PFT was performed in only 44 patients with RA-ILD. The univariate analyses and ROC curve suggested that DLCO predicted [ HR (95% CI)=1.04 (1.02,1.06), P<0.001] was a significant risk factor for the progression of RA-ILD, and the area under curve (AUC) of DLCO was 0.845 [95% CI=(0.729,0.961)]. Conclusion:UIP pattern, high titer of anti-CCP antibody, smoking, and reduced DLCO predicted % may be potential predictors for poor prognosis of RA-ILD patients.

Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers

The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization

The co-occurrence of anti-CCP positive RA with IgA nephropathy

Very few studies have explored the renal involvement in RA. This co-occurrence could be attributed to the disease itself ordrug induced. The present case study discussing the co-occurrence of anti-CCP positive RA and IgA nephropathy highlightsthe need for having a collaborative treatment approach for managing the patients.

Rheumatoid factor versus anti - cyclic citrullinated peptide antibody as screening tool for rheumatoid arthritis in an ophthalmic clinic

Patients with moderate to severe dry eyes are often screened at the Dry Eye Clinic to rule out connective tissue diseases. Rheumatoid factor (RF) is one of the screening tools to rule out rheumatoid arthritis (RA). Patients who turn out positive for the RF are often subjected to anti-CCP antibody evaluation for confirmation of disease. This article tries to highlight 3 cases of negative and anti-CCP antibody positive cases which presented to the ophthalmic clinic, unaware of their systemic status. Though RF is the cheapest modality to screen for RA, it is not always a reliable marker. One should order anti-CCP antibody for patients where suspicion is high, despite RF being normal.

Association of kir2dl2 gene with anti-cyclic citrullinated protein antibodies for serodiagnosis in rheumatoid arthritis

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.

A rare co-occurrence of anti CCP-positive rheumatoid arthritis with sacroiliitis

Sacroiliitis is considered as the most important sign of spondyloarthropathy. Rheumatoid arthritis mainly affects peripheraljoints and the involvement of sacroiliac joint is very rare. The present case study discusses the rare existence of RA andconcurrent chronic bilateral sacroiliitis.

Analysis on differential metabolites of Cervi Cornu Pantotrichum based on metabolomics / 中草药

Objective: To identify the differential metabolic small molecule substances in Cervi Cornu Pantotrichum (CCP) of different segments based on UPLC-QTOF/MS metabonomics technology, and analyze the metabolic pathways involved by differential metabolites combined with histological observation. Methods: The standard trident antler of sika deer (Cervus nippon) were treated by freeze-drying. The tissue morphology was observed by section. The tissue morphology was divided into three sections from top to bottom, VAU, VAM, and VAB. The differential metabolites were analyzed by UPLC-QTOF/MS technology, principal component analysis, and least squares discriminant analysis. Results: A total of 124 kinds of metabolic small molecular substances were identified in CCP. Based on the FC value of differential metabolites higher than 2.2, 16 substances with different relative contents in different parts of CCP were further screened, and the relative content of each substance in different parts were compared. Conclusion: This experiment is based on non-targeted metabonomics to analyze the composition of metabolic small molecules in freeze-dried CCP. By comparing the adjacent zones, it is found that there are some differences in endogenous metabolites among the zones, which provides data support for revealing their functions.

Study of Prognostic Significance of Anti Cyclic Citrullinated Peptide Antibodies in Patients with Rheumatoid Arthritis

Background: Rheumatoid arthritis is a chronic autoimmune inflammatory disease with articular and extra-articular manifestation that affects 0.5 to 1 % of total population. Aim and Objectives: To correlate Rheumatoid factor (RF) and Anti-CCP antibody in RA, to evaluate prognostic value of RF and Anti-CCP antibody in RA. Materials and methods: Retrospective study of total 50 patients admitted to our hospital from January 2018 to December 2018 was done. All patients were diagnosed as rheumatoid arthritis as per diagnostic criteria of American College of Rheumatology. All patients had symptom duration of at least one Year. Anti-CCP and lgM-RF were evaluated in all patients. Disease activity score 28 was calculated in all patients. Radiological Damage was assessed by Larsen Score. Results: Anti-CCP and RF were significantly correlated with each other and both were seen as significant independent predictors of radiological outcomes (p value 0.01 and <0.05 respectively). Combination of these two had highest risk for erosive joint damage. Conclusion: RA is more common in female. Anti-CCP antibody and RF both in combination were associated with higher probabilities of erosive disease.

Eficacia diagnóstica de anticuerpos antipéptidos citrulinados de segunda y tercera generaciones para la artritis reumatoide / Diagnostic effectiveness of anti-citrullinated peptides antibodies of second and third generations for rheumatoid arthritis

Introducción: La artritis reumatoide es una enfermedad autoinmune caracterizada por la presencia de anticuerpos contra péptidos citrulinados, que constituyen indicadores para el diagnóstico de la enfermedad. Es necesario determinar la utilidad de diferentes métodos de determinación de estos anticuerpos para el diagnóstico de pacientes cubanos con artritis reumatoide. Objetivo: Determinar la eficacia de los ensayos de determinación de anticuerpos anti-CCP2 y anti-CCP3 para el diagnóstico de pacientes cubanos con artritis reumatoide. Material y método: Participaron 101 pacientes con artritis reumatoide, 58 pacientes con otras enfermedades reumáticas e inflamatorias y 43 individuos sanos. Se determinó la eficacia diagnóstica de los anticuerpos factor reumatoideo (FR), anti-CCP2 y anti-CCP3 medidos mediante ELISA, con el cálculo de la sensibilidad, especificidad, valores predictivos positivos y negativos. Resultados: El ensayo anti-CCP2 mostró un mejor balance sensibilidad (48,5 por ciento) y especificidad (98,0 por ciento). Cuando se fijó la especificidad a 98 por ciento, se observó la menor sensibilidad para el FR (40,3 por ciento). Utilizar los ensayos anti-CCP2 y FR aumentó la especificidad a 100 por ciento. Todos los autoanticuerpos mostraron asociación con la proteína C reactiva y correlación con la velocidad de sedimentación globular. Solamente los anticuerpos anti-CCP2 no mostraron correlación con el indicador clínico de actividad DAS 28. Conclusiones: Los anticuerpos anti-CCP2 son los de mayor eficacia para el diagnóstico de pacientes cubanos con artritis reumatoide. La determinación de FR permite identificar pacientes con artritis reumatoide seronegativos de anticuerpos anti-CCP2, por lo que la combinación de ambos inmunoensayos produce una mejoría en la eficacia diagnóstica(AU)

Introduction: Rheumatoid arthritis is an autoimmune disease characterized by the presence of antibodies against citrullinated peptides, which are one of the indicators for the diagnosis of a disease. The usefulness of different methods for the determination of these antibodies in the diagnosis of Cuban patients with rheumatoid arthritis is necessary to be established. Objective: To establish the diagnostic effectiveness of the second (anti-CCP2) and third (anti-CCP3) generation assays for the determination these antibodies against citrullinated peptides in Cuban patients with rheumatoid arthritis. Material and method: 101 patients with rheumatoid arthritis, 58 patients with other rheumatic and inflammatory diseases, and 43 healthy persons participated in the study. The diagnostic efficiency of rheumatoid factor (RF), anti-CCP2 and anti-CCP3 antibodies were determined using ELISA test, by calculating sensitivity, specificity, and positive and negative predictive values. Results: The anti-CCP2 assay showed a better balance of sensitivity (48.5 percent) and specificity (98.0 percent). The lower sensibility was observed for RF (40.3 percent) when the specificity was set at 98 percent. Specificity increased to 100 percent when anti-CCP2 and RF assays were used. All autoantibodies showed association with C-reactive protein and correlation with erythrocyte sedimentation rate. Only anti-CCP2 antibodies showed no correlation with the DAS28 clinical indicator. Conclusions: Anti-CCP2 antibodies are the ones of greater effectiveness in the diagnosis of Cuban patients with rheumatoid arthritis. RF identification allows to identify seronegative anti-CCP2 patients; therefore, the combination of both immunoassays leads to an improvement in the diagnostic effectiveness(AU)

Manifestación atípica de enfermedad de Still: Reporte de un caso / Atypical manifestation of Still disease: Case report

La enfermedad de Still del adulto (ESA) es un proceso inflamatorio sistémico, de etiología desconocida, que se caracteriza por fiebre, artritis y eritema evanescente, además de valores elevados de ferritina sérica. Sin embargo, hasta la fecha, no hay una prueba definitiva de laboratorio o de imagen disponible para su diagnóstico, por lo tanto la ESA es un diagnóstico de exclusión. Presentamos el caso de una mujer de 44 años con manifestación cutánea atípica de ESA y cuadro clínico de 1 año de evolución caracterizado por fiebre de 40°C, linfadenopatía, hiperferritinemia, y que en la sistemática de estudio presentó positividad para anti-CCP (anticuerpo antipéptido cíclico citrulinado).

Adult Still's disease (ASD) is a systemic inflammatory process, of unknown etiology, characterized by fever, arthritis and evanescent erythema, in addition to elevated serum ferritin values. However, to date, there is no definitive laboratory or imaging test available to diagnose it, therefore ASD is a diagnosis of exclusion. We present the case of a 44-year-old woman with atypical cutaneous manifestation of ESA and positivity of ACPA (anti-cyclic citrullinated peptide antibody).

Psychological Capital Questionnaire - short version (PCQ-12): evidence of validity of the Brazilian version / Questionário de Capital Psicológico - versão reduzida (QCP-12): evidências de validade da versão brasileira / Cuestionário de Capital Psicológico - versión reducida (CCP-12): evidencias de validez de la versión brasileña

This study aimed to show evidence of validity for the Brazilian short version (12 items) of the Psychological Capital Questionnaire (PCQ-12). Three independent samples participated in the study, totaling 1771 subjects (64.3% women, 32.9% men and 2.9% undeclared), aged 18-79 years (M = 38.59, SD = 12.98). Confirmatory factor analyses showed acceptable adjustment indices for the four-factor structure (self-efficacy, hope, resilience and optimism) and for a second-order structure with a general factor of psychological capital explaining the four primary factors. Multi-group confirmatory factor analyses found configural, metric and scalar invariance of the measure for the different samples as well as for men and women. Finally, convergent validity analyses found a positive and moderate correlation of PCQ-12 with satisfaction with life and subjective happiness, as well as a negative and moderate correlation with perceived stress and depression. (AU)

Esse estudo tem por objetivo apresentar evidências de validade para a versão brasileira reduzida (12 itens) do Questionário de Capital Psicológico (QCP-12). Participaram do estudo três amostras independentes, totalizando 1771 sujeitos (64,3% mulheres, 32,9% homens, e 2,9% não declarados), com idades entre 18 a 79 anos (M = 38,59; DP = 12,98). Análises fatoriais confirmatórias apresentaram índices de ajuste aceitáveis para a estrutura de quatro fatores (autoeficácia, esperança, resiliência e otimismo) correlacionados e para uma estrutura de segunda ordem, com um fator geral de capital psicológico explicando os quatro fatores de primeira ordem. Análises fatoriais confirmatórias multigrupo encontraram invariância configural, métrica e escalar da medida para as diferentes amostras bem como para homens e mulheres. Por fim, análises de validade convergente encontraram correlação positiva e moderada do QCP-12 com a satisfação com a vida e a felicidade subjetiva, e negativa e moderada com o estresse percebido e a depressão. (AU)

Este estudio tiene como objetivo presentar evidencias de validez de la versión brasileña reducida (12 ítems) del Cuestionario de Capital Psicológico (CCP-12). El estudio incluyó tres muestras independientes, con un total de 1771 individuos (64,3% mujeres, 32,9% hombres y 2,9% no declarados), con edades entre 18 a 79 años (M = 38,59, SD = 12,98). El análisis factorial confirmatorio mostró índices de ajuste aceptable para estructura de cuatro factores correlacionados (autoeficacia, esperanza, resiliencia y optimismo) y para una estructura de segundo orden con un factor general de capital psicológico que explica los cuatro factores de primer orden. Análisis factorial confirmatorio multigrupo encontró invariancia configural, métrica y escalar de la medida para las diferentes muestras, tanto para hombres como mujeres. Por fin, análisis de validez convergente encontraron correlación positiva y moderada de CCP-12 de satisfacción con la vida y felicidad subjetiva, y correlación negativa y moderada con el estrés percibido y la depresión. (AU)

Expression of calreticulin and its relationship with autoantibodies and inflammatory cytokines in early rheumatoid arthritis / 天津医药

Objective To investigate the expression of calreticulin and its correlation with autoantibodies and inflammatory cytokines in patients with early rheumatoid arthritis (RA). Methods Serum samples were obtained from 106 patients with early active RA, 95 patients with stable RA, 85 osteoarthritis (OA) and 80 healthy controls (HC). Serum levels of calreticulin, anti- cyclic peptide antibody (CCP), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immnuosorbent assay (ELISA). The serum level of rheumatoid factor (RF) was detected by immunoturbidimetry. The correlations between serum calreticulin and inflammatory cytokines were evaluated using Spearman's rank correlation test. Results Serum levels of calreticulin were significantly higher in patients with early active RA [(5.84±2.62)μg/L] than those in patients with stable RA [(4.26±1.42)μg/L], patients with OA [(3.92±1.10)μg/L] and HC [(3.86 ± 0.91)μg/L] (P<0.001). There were no statistical differences in serum levels of calreticulin between stable RA, OA and HC groups (P>0.05). Serum levels of calreticulin were significantly higher in RF-positive RA patients than those of RF-negative RA patients [(6.12±2.87)μg/L vs. (4.92±1.22)μg/L, P=0.045]. Serum calreticulin levels were also significantly higher in anti-CCP-positive RA patients than those of anti-CCP-negative RA patients [(6.39±2.93)μg/L vs. (4.69±1.17)μg/L, P=0.002]. The serum level of calreticulin was positively correlated with IL-1β (rs=0.386, P=0.009), IL-6 (rs=0.405, P=0.006) and TNF-α(rs=0.428, P=0.003) in early active RA patients. Conclusion The elevated serum level of calreticulin is related to autoantibodies and inflammatory cytokines in early RA patients, suggesting that calreticulin can be used as a potential biomarker for early diagnosis and prognosis of RA.

Analysis of four serum biomarkers in rheumatoid arthritis: association with extra articular manifestations in patients and arthralgia in relatives / Análise de quatro marcadores sorológicos na artrite reumatoide: associação com manifestações extra-articulares no paciente e artralgia em familiares

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.

Anti-CCP antibodies are not a marker of severity in established rheumatoid arthritis: a magnetic resonance imaging study / O anti-CCP não é um marcador de gravidade da artrite reumatoide estabelecida: um estudo de ressonância magnética

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.

Clinical significance of serum 14-3-3η protein and auto-antibodies detection in rheumatoid arthritis / 中国免疫学杂志

Objective:To explore the clinical value of detecting serum 14-3-3η and auto-antibodies in rheumatoid arthritis (RA),and compare their performance in RA diagnosis.Methods: Serum samples of 134 RA patients,90 non-RA inflammatory arthropathy patients,70 of whom with osteoarthritis(OA)and 20 with ankylosing spondylitis(AS),and 40 healthy controls from the second affiliated hospital of Nanchang University were collected.Concentrations of 14-3-3η,anti-CCP,anti-RA33,anti-Sa were detected with enzyme linked immunosorbent assay(ELISA),with RF detected by immunonephelometry.Diagnostic utilities of them for RA were evaluated and compared then.Results:① Serum levels of 14-3-3η,anti-CCP,anti-RA33,anti-Sa and RF were significantly higher in patients with RA than non-RA inflammatory arthropathy patients and healthy controls,the differences between groups were statistically significant;② ROC curves were conducted according to the serum levels detected.The AUC of 14-3-3η,anti-CCP,anti-RA33,anti-Sa and RF were 0.831(95% CI:0.782-0.881),0.852(95% CI:0.802-0.901),0.615(95% CI:0.546-0.684),0.706(95% CI:0.643-0.770)and 0.739(95% CI:0.676-0.802)respectively,with P values<0.01.Among all index,only anti-CCP and 14-3-3η were of moderate diagnostic value,at the threshold of 24.10 U/ml and 2.59 ng/ml individually;③anti-Sa was of highest specificity and RF was of highest sensitivity among all indexes detected;the specificity of 14-3-3η was merely moderately inferior to anti-Sa and anti-RA33,but its sensitivity was superior to them both.Conclusion:Serume14-3-3η,anti-CCP,anti-RA33,anti-Sa and RF levels increased remarkably in patients with RA,and contributed to RA diagnosis.Meanwhile,14-3-3η was advantageous,to some extent,in the sensitivity and specificity over auto-antibodies,and can be utilized as a reference index in diagnosing RA.

Diagnostic Value and Significance of the HLA-DR53,Anti-Sa and Anti-CCP Antibody Factors Combination in Rheumatoid Arthritis / 现代检验医学杂志

Objective To explore the value of human leucocyte antigen-DR53 (HLA-DR53),anti-Sa antibody and anti-cyclic citrullinated peptide antibody(anti-CCP) factors combination in rheumatoid arthritis.Methods 170 patients with rheumatoid arthritis and 50 healthy individuals in the hospital were chosen.The levels of HLA-DR53 by PCR-SSP,the levels of anti-Sa and anti-CCP by ELISA,compared their diagnostic value by consistency analysis and joint detection analysis.Results The sensibility of anti-Sa,HLA-DR53 and anti-CCP in RA were 44.07％ (P =0.00,x2 =165.214),68.65 ％ (P =0.00,x2 =9.837) and 79.45 ％ (P=0.00,x2=48.028).Consistency analysis in RA,HLA DR53,anti-CCP and anti-Sa highly consistent,OR were 3.94,38.6 and 184.52.The sensitivity and Youden index of anti-CCP were the highest.The sensitivity of anti Sa and anti-CCP parallelled was 88.51 ％.The sensitivity of HLA-DR53 and anti-CCP parallelled was 93.56％,and the spe cificity of anti-Sa and anti-CCP of RA were 100％.Conclusion There is a certain correlation between HLA-DR53,anti-Sa and anti-CCP antibody,which are related risk factors of RA,co-detection will improve the diagnosis of RA.

Application of combined detection of AKA antibody,anti-CCP antibody,anti-RA33antibody,RF and ESR in rheumatoid arthritis / 国际检验医学杂志

Objective To investigate the application value of combined detection of antikeratin (AKA) antibody,anti-cyclic citrullinated peptide(anti-CCP) antibody,anti-RA33 antibody,RF and ESR in the diagnosis of rheumatoid arthritis(RA).Methods One hundred cases of RA and 60 cases of suspected RA in our hospital from June 2014 to May 2015 were collected.One hundred and twenty cases of non-RA other autoimmune diseases served as the control group.The indirect immunofluorescence assay (IFA) was used to detect anti-KA antibody,anti-CCP antibody and anti-RA33 antibody were detected by using ELISA.The rate scatter turbid assay was used to detect RF.The Westergren method was used to detect ESR.The diagnostic performance of each diagnostic indicator was evaluated.Results The detection rates of anti-KA antibody,anti-CCP antibody,anti-RA33 antibody,RF and ESR in the RA group were in turn 64%,75%,44%,84% and 51% respectively,the detection rate(sensitivity) of 5-indicator parallel detection were 97%, the specificity of 5-indicator series detection was 89.2%;in the suspected RA group,the detection rates of 5-indicator were in turn 16.7%, 31.7%,13.3%,20%,15% respectively,which in the control group were in turn 0.8%,2.5%,1.7%,0.8% and 5.8% respectively.The detection rates of 5-indicator in the RA group was significantly higher than that in the suspected RA group,showing extremely significant difference (P<0.001),the detection rate of 5-indicator had extremely significant difference between the suspected RA group and control group (P<0.001),the sensitivity of five-indicator parallel detection was 97%,which was significantly higher than that of single indicator detection (P<0.05),the detection specificity of 5-indicator series detection was up to 100%,which was also significantly higher than that of single indicator detection (P<0.05),the missed diagnosis rate of parallel detection was minimal,while the negative predictive value was highest,the misdiagnosis rate of series detection was lowest,the positive predictive value was highest,the Youden index of parallel detection was largest.Conclusion The single detection of anti-CCP antibody and RF have good sensitivity and specificity, but 5-indicator combined detection has higher sensitivity and specificity,which can better reduce the missed diagnosis rate and misdiagnosis rate,can greatly improve the efficiency of diagnosis,and has an important clinical significance for the early diagnosis of RA.

Clinical significance of serum anti-CCP antibody and TNF-α expression in patients with rheumatoid arthritis / 重庆医学

Objective To investigate the value of serum anti-CCP antibody and TNF-α in the diagnosis and therapeutic effect evaluation of rheumatoid arthritis(RA).Methods One hundred and sixty-eight RA patients in our hospital from January 2012 to December 2015 were selected and included 86 cases of active stage(active group)and 80 cases of remission stage(remission group).Other 80 outpatient healthy controls served as the control group.The levels of RF,anti-CCP antibody and TNF-α in the active group,remission group and control group were measured by using the immunoadsorption and ELISA.Then the detection results were analyzed.Results The serum anti-CCP antibody and TNF-α levels in the active group and remission group were higher than those in the control group,moreover the serum anti-CCP antibody and TNF-α levels in the active group were significantly higher than those in the remission group,the difference was statistically significant(P＜0.05).Comparing the RA patients with the control group,the sensitivity and specificity of combined detection of anti-CCP antibody and TNF-α was 73.8％ and 97.5％,which were higher than those of other 2-index combined detection,the difference was statistically significant(P＜0.05).The serum TNF-α level was positively correlated with the DAS28 score(P＜0.01).Conclusion The combined detection of serum anti-CCP antibody and TNF-α has an important clinical value for the RA diagnosis and disease condition monitoring.

Developing Food Safety Education Program for Employees at School Foodservice Implementing HACCP / 대한지역사회영양학회지

OBJECTIVES: This study was performed to develop a food safety education program for school foodservice employees and evaluate its effectiveness. METHODS: Food safety education programs were made into two levels; one for new employees in school foodservice and another for employees in charge of Critical Control Point (CCP) monitoring. The programs were for 40-minute-long lecture using PowerPoint. The effectiveness of these programs were assessed based on eleven evaluation items by school foodservice dieticians (n=30) and the Hazard Analysis Critical Control Point (HACCP) specialist (n=13). All statistical analyses are conducted by SPSS package program (ver 20.0). RESULTS: According to the results of evaluating the food safety education program by dietitian and HACCP specialist, the overall satisfaction score was 4.14, evaluated by 5 point scale. There were no significant difference in results of evaluation between dieticians and HACCP specialists. The score of 'it is helpful to work' and 'pictures, images and charts are pertinent to study' were higher than others while the score of 'education contents is pleasant and interesting' and 'screen is pleasant and interesting' were the lowest among all evaluation items. CONCLUSIONS: To increase the school foodservice quality, employees should be offered regular food safety education and training through effective education media including prerequisite program and HACCP manual for school foodservice.