ß2-Microglobulina un biomarcador de actividad en pacientes con lupus eritematoso sistémico / ß2-Microglobulin a biomarker of disease activity in systemic lupus erythematosus patients

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, caracterizada por daño crónico a órganos o sistemas, caracterizada por la activación anormal de linfocitos T y/o B debido a una presentación y reconocimiento antigénico anormal que favorece la producción de citoquinas pro inflamatorias y auto-anticuerpos fijadores de complemento que promueven la formación y depósito de complejos inmunes con el consecuente daño celular. También se caracteriza por periodos cíclicos de brote y remisión de la enfermedad. La búsqueda de biomarcadores clínicamente útiles para conocer de manera anticipada un brote de la enfermedad aún está en curso, entre los biomarcadores se sugiere que la ß2-microglobulina (ß2M) puede ser útil para evaluar la actividad del LES. El objetivo del estudio fue correlacionar la concentración de ß2M sérica con los marcadores comúnmente evaluados para establecer la actividad del LES. MATERIAL Y MÉTODO La población de estudio consistió en 119 pacientes con LES activo y no activo (57 pacientes control, 42 pacientes con LES activo y 20 pacientes con LES inactivo) los cuales firmaron su consentimiento para participar en el estudio. El grupo control correspondía a pacientes sin antecedentes clínicos y familiares de enfermedad autoinmune. El grupo de pacientes con LES cumplía al menos 4 criterios de clasificación de LES del Colegio Americano de Reumatología. La concentración de ß2M se midió por ELISA. La actividad del LES fue evaluada mediante parámetros clínicos, niveles séricos de anti-ds-DNA, fracción del complemento C3 y C4. Los niveles de ß2M fueron asociados con marcadores serológicos de anti-nucleosoma, anti-C1q y creatinina. RESULTADOS El estudio reveló diferencia significativa en los niveles séricos de ß2M (p<0.001) entre los tres grupos de estudio, en los pacientes con LES activo se observó una mediana 5,4 ug/mL, P25 3,17 ug/mL P75 6,72 ug/mL; el grupo control presentó una mediana menor al grupo LES activo de 1,8 ug/mL P25 1,6 ug/mL P75 1,9 ug/mL y al grupo de LES inactivo con mediana de 3,25 ug/mL P25 2,63 ug/mL P75 3,55 ug/mL. Además, se observó correlación de resultados entre la concentración de ß2M y niveles de anti-ds-DNA (p<0,01; r=0,595) y niveles séricos del complemento C3 (p<0,01; r=−0,519) y C4 (p=0,019; r=−0,345). CONCLUSIONES La medición de la ß2M sérica puede ser un biomarcador útil para evaluar la actividad de la enfermedad del LES siempre y cuando sea empleado con otros test de laboratorio que se utilizan de manera rutinaria para evaluar la actividad de LES.

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by chronic damage to organs or systems, due to abnormal activation of T and/or B-lymphocytes, caused by abnormal antigenic presentation and recognition that gives the production of pro- inflammatory cytokines and complement-fixing autoantibodies that promote formation of immune complexes and cellular damage. It is also characterized by cyclic periods of activation and remission. The search for clinically useful biomarkers for early knowledge of disease outbreak is going; biomarkers suggest that ß2-microglobulin (ß2M) is useful for evaluating the activity of the SLE. The objective of this study was to analyze the relationship between serum ß2M concentrations with markers of SLE activity. MATERIAL AND METHODS One hundred nineteen patients were included (control 57, active SLE 42 and inactive SLE 20) who signed their consent to participate in the study. The control group corresponded to patients without clinical and family history of autoimmune disease. The patients group with SLE met at least four criteria of the American Society of Rheumatology for lupus diagnostic. ß2M concentration was measured using an ELISA test. SLE activity was evaluated by clinical parameters, serum levels of anti-ds-DNA, complement levels C3 and C4. ß2M levels were associated with anti-nucleosome, anti-C1q and creatinine. RESULTS The study revealed a significant difference between the three study groups (p<0,01), in active SLE group a median 5,4 ug/mL, P25 3,17 ug/mL P75 6,72 ug/mL was observed. The control group presented a lower median to the active SLE group of 1,8 ug/mL P25 1,6 ug/mL P75 1,9 ug/mL and to the inactive SLE group with a median 3,25 ug/mL P25 2,63 ug/mL P75 3,55 ug/mL. In addition, correlation of results was observed between ß2M concentration and anti-ds-DNA levels (p<0,01, r=0,595) and complement serum level C3 (p<0,01, r=-0,519) and C4 (p=0,019; r=-0,345). CONCLUSION ß2M serum measurement can be a useful biomarker to assess the SLE activity as long as it is used with other laboratory tests that are routinely used to evaluate the activity of SLE.

Relationship between neutrophil-to-lymphocyte ratio and systemic lupus erythematosus: a meta-analysis

Systemic lupus erythematosus (SLE) is a chronic systematic autoimmune disease. Current methods of diagnosing SLE or evaluating its activity are complex and expensive. Numerous studies have suggested that neutrophil-to-lymphocyte ratio (NLR) is closely correlated with the presence of SLE and its activity, suggesting that it may serve as a diagnostic and monitoring indicator for SLE. Therefore, we performed a meta-analysis to systematically assess the association between NLR and SLE. We performed a literature search until 12 April 2019 in the PubMed, Web of Science, and China National Knowledge Infrastructure databases. Cross-sectional studies comparing the NLR of SLE patients versus those of healthy controls, of active versus inactive SLE patients, and of SLE patients with versus without lupus nephritis were considered for inclusion. Mean intergroup NLR differences were estimated using standardized mean differences and their 95% confidence intervals. Study quality was assessed using the Agency for Healthcare Research and Quality instrument for cross-sectional studies. Fourteen studies with 1,781 SLE patients and 1,330 healthy controls were included in this meta-analysis. The pooled results showed that the NLR was significantly higher in SLE patients than in healthy controls, in active SLE patients than in inactive SLE patients, and in SLE patients with lupus nephritis than in those without lupus nephritis. NLR may be an indicator for monitoring disease activity and reflecting renal involvement in SLE patients. Nevertheless, more high-quality studies are warranted to further validate our findings.

Analysis on the risk factors for organ damage in patients with systemic lupus erythematosus: a cross-sectional single-center experience

ABSTRACT BACKGROUND: Organ damage in patients with systemic lupus erythematosus (SLE) occurs as a consequence of the disease itself, the therapy applied and the accompanying conditions and complications. Organ damage predicts further organ damage and is associated with an increased risk of death. OBJECTIVE: This study aimed to assess the degree of irreversible organ changes in SLE patients, using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI); to establish correlations between organ damage and disease activity, quality of life, intensity of fatigue and serological factors; and to ascertain the risk factors for organ damage. DESIGN AND SETTING: Cross-sectional single-center study conducted at the Institute for Treatment and Rehabilitation "Niška Banja", Niš, Serbia. METHODS: 83 patients with SLE were enrolled: 58 patients formed the group with organ damage (SDI ≥ 1), and 25 patients without organ damage served as controls (SDI = 0). RESULTS: Organ damage correlated with age (P = 0.002), disease duration (P = 0.015), disease activity (grade 1, P = 0.014; and grade 2, P = 0.007), poor quality of life, severe fatigue (P = 0.047) and treatment with azathioprine (P = 0.037). The following factors were protective: use of hydroxychloroquine (P = 0.048) and higher scores obtained for the physical (P = 0.011), mental (P = 0.022) and general health (P = 0.008) domains. CONCLUSION: It is very important to evaluate risk factors for organ damage in the body, including physicians' overall assessment, to try to positively influence better treatment outcomes.

Altered peripheral lymphocyte subsets in untreated systemic lupus erythematosus patients with infections

The leading cause of death in systemic lupus erythematosus (SLE) patients is infection. The objective of this study was to evaluate the distribution of lymphocyte subsets in untreated SLE patients with infections. This was a cross-sectional study. Data from January 2017 to May 2018 were collected. Flow cytometry was used to measure the peripheral lymphocyte subsets including CD3+T cells, CD4+T cells, CD8+T cells, CD19+B cells, CD3-CD16+CD56NK cells, and CD3+CD16+CD56NKT cells in 25 healthy controls and 52 treatment-naive SLE patients, among whom 13 were complicated with infections. Association between the lymphocyte subsets and infections was further analyzed. SLE patients with infections (n=13) showed a significantly higher incidence rate of fever (84.6 vs 28.2%) and serositis (84.6 vs 23.1%), increased level of erythrocyte sedimentation rate (60.5±30.1 vs 37.4±27.1 mm/h), serum C-reactive protein (CRP) (102.7±94.9 vs 9.4±14.9 mg/L), procalcitonin (PCT) (1.07±0.08 vs 0.16±0.13 μg/L), and lower blood hemoglobin (Hb) (93.0±20.5 vs 110.4±16.0 g/L) level compared with non-infection patients (n=39) (all P<0.05). In comparison with non-infectious SLE patients (387.9±261.6/μL), CD4+T cells count decreased significantly in infectious SLE patients (217.8±150.4/μL) (P<0.05), and it was negatively correlated with infection-related indicators including PCT (r=−0.573, P=0.041) and CRP (r=−0.596, P=0.032) levels. Our findings suggested that abnormalities of peripheral lymphocyte subsets were related to the immune disorder of lupus itself, regardless of immunosuppressive treatment. Monitoring lymphocyte subsets, especially CD4+T cells, may be helpful for identifying the presence of infection in SLE patients.

Evaluation of serum interleukin-34, as a marker of disease activity in systemic lupus erythematosus and rheumatoid arthritis patients

Aim of the work: To evaluate the role of IL-34 in the pathogenesis of SLE and RA and to assess its role as a biomarker of disease activity. Subjects and methods: This study was carried out on 29 patients with SLE, 29 patients with RA, and 29 healthy control subjects. SLE disease activity was measured by systemic lupus erythematosus disease activity index (SLEDAI). RA disease activity was measured by 28-joint disease activity score (DAS-28). Serum IL-34 was measured by enzyme-linked immunosorbent assay (ELISA) . Results: There was highly significant elevation in IL-34 level in SLE and RA when compared to control group (p<0.001). IL34 level did not differ significantly between SLE and RA groups (p˃ 0.05). There was a significant positive correlation between IL-34 level and SLEDAI in SLE patients as well DAS 28 score in RA patients. The highest level was detected in patients with high disease activity. There was statistically significant correlation between IL-34 levels and ESR, CRP, and anti-ds DNA antibodies but inversely correlated with C3 in SLE patients. There was also statistically significant correlation between IL-34 levels and ESR, CRP RF, and anti CCP antibodies in RA patients. Conclusion: IL-34 could be useful marker for disease activity in SLE and RA

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

Abstract Background: Adaptive immune cells, including CD4+CD69+ and CD4+CD25+FoxP3+ regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4+CD25+FoxP3+ Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4+CD69+ and CD4+CD25+FoxP3+ T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4+CD69+ T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4+ CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFβ1 (p = 0.038). Conclusion: Increased numbers of CD4+CD69+ T cells and reduced numbers of CD4+CD25+FoxP3+ Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.

Cut-off values of immunological tests to identify patients at high risk of severe lupus nephritis

Cut-off values for anti-dsDNA, anti-nucleosome and anti-C1q antibodies tests and for complement-mediated hemolytic activity (CH50) were explored to identify patients with high risk of developing severe lupus nephritis (LN). Forty-one patients with confirmed systemic lupus erythematosus (SLE) were identified; their levels for the three antibodies and complement had been measured on a same serum sample. These patients were classified based on the presence of renal involvem ent; sixteen had active proliferative LN. With the cut-off values accepted in the laboratory for SLE diagnosis (anti-dsDNA > 100 UI/ml, anti-nucleosome > 50 U/ ml or CH50 < 190 UCH50%) no significant differences were found between patients with and without LN. Anti-C1q > 40 U/ml showed a statistically significant association with LN and had 80% of specificity. Cut-off values for LN identified by Receiver Operating Characteristic curves (ROC) were higher for anti-dsDNA (> 455 IU/ml) and anti-nucleosome (>107 U/ml), lower for CH50 (< 150 UCH50%) and, for anti-C1q (> 41 U/ml) coincided with the cut-off values accepted for SLE. Anti-C1q > 134 U/ml had a 92% of specificity, 56% of sensibility and was associated with a fifteen-fold increased risk of LN. The simultaneous presence of anti-nucleosome > 107 U/ml and anti-C1q > 134 U/ml was associated with a 27-fold higher probability for LN. According to these results, the cut-off values used to detect SLE activity could be inadequate to identify patients at high risk of severe LN.

Se exploraron valores de corte para los ensayos de anti-ADNdc, anti-nucleosoma, anti-C1q y complemento hemolítico total (CH50) capaces de identificar los casos con mayor riesgo de nefritis lúpica (NL) grave. Se seleccionaron 41 pacientes ≥ 16 años con lupus eritematoso sistémico (LES) confirmado que tenían titulados los niveles de los tres anticuerpos y CH50, en una misma muestra de suero. Fueron clasificados según presencia de compromiso renal; 16 presentaron formas proliferativas de NL activa. Con los valores de corte aceptados por el laboratorio para el diagnóstico de LES (anti-ADNdc > 100 UI/ml, anti-nucleosoma > 50 U/ml o un CH50 < 190 UCH50%) no se encontraron diferencias significativas entre casos con y sin NL. Un anti-C1q > 40 U/ml tuvo una especificidad del 80% y mostró una asociación estadísticamente significativa con NL. Al aplicar curvas Receiver Operating Characteristic (ROC) para NL, se identificaron valores de corte más altos para anti-ADNdc (> 455 IU/ml) y anti-nucleosoma (> 107 U/ml), más bajo para CH50 (< 150 UCH50%) y para el anti-C1q (> 41 U/ml) coincidió con el aceptado para diagnóstico de LES. Un anti-C1q > 134 U/ml presentó una sensibilidad del 56%, una especificidad del 92% y se asoció con quince veces más riesgo de NL. La presencia simultánea de anti-C1q > 134 U/ml y anti-nucleosoma > 107 U/ml se asoció 27 veces más riesgo de NL. De acuerdo a estos resultados los valores de corte empleados para actividad en pacientes con LES podrían resultar inadecuados para identificar pacientes con mayor riesgo de NL grave.

T cell subsets and immunoglobulin G levels are associated with the infection status of systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.

Omega-3 fatty acids, inflammatory status and biochemical markers of patients with systemic lupus erythematosus: a pilot study / Ácidos graxos ômega-3, estado inflamatório e marcadores bioquímicos de pacientes com lúpus eritematoso sistêmico: estudo piloto

Abstract Background: Studies have shown that omega-3 fatty acids reduce the concentrations of eicosanoids, cytokines, chemokines, C-reactive protein (CRP) and other inflammatory mediators. Objective: To investigate the effects of omega-3 fatty acids on circulating levels of inflammatory mediators and biochemical markers in women with systemic lupus erythematosus (SLE). Methods: Experimental clinical study (clinical trial: NCT02524795); 49 women with SLE (ACR1982/1997) were randomized: 22 to the omega-3 group (daily intake of 1080 mg EPA + 200 mg DHA, for 12 weeks) and 27 to the control group. The inflammatory mediators and biochemical markers at T0 and T1 in omega-3 group were compared using Wilcoxon test. U-Mann-Whitney test was used to compare variations of measured variables [ΔV = pre-treatment (T0) − post-treatment (T1) concentrations] between groups. p < 0.05 was considered significant. Results: The median (interquartile range - IQR) of age was 37 (29-48) years old, of disease duration was 7 (4-13) years, and of SLEDAI-2K was 1 (0-2). The median (IQR) of variation in CRP levels between the two groups showed a decrease in omega-3 group while there was an increase in control group (p = 0.008). The serum concentrations of IL-6 and IL-10, leptin and adiponectin did not change after a 12 week treatment. Conclusions: Supplementation with omega-3 had no impact on serum concentrations of IL-6, IL-10, leptin and adiponectin in women with SLE and low disease activity. There was a significant decrease of CRP levels as well as evidence that omega-3 may impact total and LDL-cholesterol.

Resumo Introdução: Estudos têm mostrado que os ácidos graxos ômega-3 reduzem as concentrações de eicosanoides, citocinas, quimiocinas, proteína C-reativa (PCR) e outros mediadores inflamatórios. Objetivo: Investigar os efeitos dos ácidos graxos ômega-3 sobre os níveis circulantes de mediadores inflamatórios e marcadores bioquímicos em mulheres com lúpus eritematoso sistêmico (LES). Métodos: Ensaio clínico randomizado (ensaio clínico: NCT02524795); randomizaram-se 49 mulheres com LES (ACR1982/1997): 22 para o grupo ômega-3 (dose diária de 1.080 mg de EPA + 200 mg de DHA durante 12 semanas) e 27 para o grupo controle. Os mediadores inflamatórios e marcadores bioquímicos em T0 e T1 no grupo ômega-3 foram comparados pelo teste de Wilcoxon. O teste U de Mann-Whitney foi usado para comparar variações das variáveis mensuradas [ΔV = concentrações pré-tratamento (T0) menos concentrações pós-tratamento (T1)] entre os grupos. Um p < 0,05 foi considerado significativo. Resultados: A mediana (intervalo interquartil-IIQ) da idade foi de 37 anos (29-48), a duração da doença foi de sete anos (4-13) anos e o Systemic Lupus Disease Activity Index (Sledai-2 K) foi de 1 (0-2). A mediana (IIQ) da variação nos níveis de PCR entre os dois grupos mostrou um decréscimo no grupo ômega-3, enquanto houve um aumento no grupo controle (p = 0,008). As concentrações séricas de IL-6 e IL-10, leptina e adiponectina não se alteraram após um tratamento de 12 semanas. Conclusões: A suplementação de ômega-3 não teve impacto sobre as concentrações séricas de IL-6, IL-10, leptina e adiponectina em mulheres com LES e baixa atividade da doença. Houve uma diminuição significativa nos níveis de PCR, bem como evidências de que o ômega-3 pode impactar sobre o colesterol total e LDL.

ANCA-Positive pauci-immune crescentic glomerulonephritis in a patient with systemic lupus erythematosus / Glomerulonefrite rapidamente progressiva ANCA-Positiva pauci-imune em paciente com lúpus eritematoso sistêmico

Abstract The pauci-immune crescentic glomerulonephritis (PICGN) is generally associated with small-vessel vasculitis with a few reported cases associated with other autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We present the case of a female 34-year-old patient with acute kidney injury symptoms with indication for renal replacement therapy in the context of clinical SLE diagnosis. A kidney biopsy was conducted and it was found that most glomeruli showed some segmental sclerosis with synechia to the Bowman's capsule. 67% of the glomeruli had fibroepithelial crescents. Moreover, the interstitial space had a moderate lymphomononuclear infiltration and mild fibrosis. In the arterioles, there were walls thickened by subintimal sclerosis. Direct immunofluorescence detected limited IgM and C3 deposits in capillary loops and negative mensangium for IgG, IgA and C1q. A therapy using corticosteroids and intravenous cyclophosphamide was initiated with stable evolution. PICGN associated with SLE is a rare pathology with clinical presentation, varied evolution and without a standard medical treatment.

Resumo A glomerulonefrite rapidamente progressiva pauci-imune apresenta-se geralmente associada a vasculite de pequenos vasos, com poucos casos associados a outras doenças imunes como o lúpus eritematoso sistêmico (LES). Apresentamos no presente artigo o caso de uma mulher de 34 anos de idade com sintomas de insuficiência renal aguda e indicação de terapia renal substitutiva, no contexto de diagnóstico clínico de LES. A biópsia renal realizada revelou que a maioria dos glomérulos apresentavam um certo grau de esclerose segmentar e sinéquias com a cápsula de Bowman. Sessenta e sete por cento dos glomérulos apresentava crescentes fibroepiteliais. Além disso, o espaço intersticial exibia infiltrado linfomononuclear moderado e fibrose discreta. Nas arteríolas, as paredes encontravam-se espessadas por esclerose subintimal. A imunofluorescência direta detectou depósitos limitados de IgM e C3 nas alças capilares e mesângio negativo para IgG, IgA e C1q. Tratamento com corticosteroides e ciclofosfamida endovenosa foi iniciado com evolução estável. A glomerulonefrite rapidamente progressiva pauci-imune associada a LES é uma patologia rara com manifestação clínica e evolução variada, sem tratamento clínico padronizado.

Prevalence of thyroid autoantibodies in patients with systematic autoimmune rheumatic diseases. Cross-sectional study

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.

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

Childhood-onset systemic lupus erythematosus (cSLE) exhibits an aggressive clinical phenotype and severe complications. This could be due to a pro-inflammatory cytokine milieu. Therefore, we determined plasma levels of Th1 (IL-2, IFN-γ, TNF), Th2 (IL-4), Th17 (IL-17A, IL-6), and Treg (IL-10) cytokines in a cohort of cSLE patients and healthy controls, and we evaluated the association between these cytokines and disease activity. We conducted a cross-sectional study with 51 cSLE patients from two pediatric rheumatology services. Ten cSLE patients participated in a longitudinal follow-up study. Blood samples were collected from the same patient during active and inactive disease. Disease activity was evaluated according to SLE Disease Activity Index 2000 (SLEDAI-2K). Cytokines levels were measured by cytometric bead array technique. cSLE patients had higher IL-6 (P<0.001) and IL-10 (P<0.001) levels than healthy controls. Patients with active disease had higher IL-6 and IL-10 levels than patients with inactive disease (P=0.001 and P=0.014, respectively) and the control group (both P<0.001). IL-6 (P=0.022), IL-10 (P=0.013), and IL-17A (P=0.041) levels were significantly higher during active than inactive disease. Linear regression analysis revealed IL-6 (P=0.002, 95%CI=0.006-0.025) and IL-10 (P=0.01 95%CI=0.021-0.150) as independent factors for increased SLEDAI-2K. IL-6, IL-10, and IL-17A are candidate biomarkers for disease activity in cSLE patients. This is the first longitudinal study to support their pivotal role in the pathogenesis of the disease.

Mean platelet volume is decreased in adults with active lupus disease / O volume plaquetário médio está reduzido em adultos com lúpus ativo

ABSTRACT Background: Only a few biomarkers are available for assessing disease activity in systemic lupus erythematosus (SLE). Mean platelet volume (MPV) has been recently studied as an inflammatory biomarker. It is currently unclear whether MPV may also play a role as a biomarker of disease activity in adult patients with SLE. Objective: We investigated the association between MPV and disease activity in adult patients with SLE. Methods: In this retrospective study, we compared two groups of adult patients divided according to disease activity (36 per group). Subjects were age- and gender-matched. Results: MPV was significantly decreased with respect to those of inactive patients (7.16 ± 1.39 vs. 8.16 ± 1.50, p = 0.005). At a cutoff level of 8.32 fL, MPV has a sensitivity of 86% and a specificity of 41% for the detection of disease activity. A modest positive correlation was found between MPV and albumin (r = 0.407, p = 0.001), which in turn is inversely associated with disease activity. Conclusions: In summary, MPV is decreased in adult patients with active lupus disease, and positively correlated with albumin, another biomarker of disease activity. Prospective studies are needed to evaluate the prognostic value of this biomarker.

RESUMO Antecedentes: Existem poucos biomarcadores disponíveis para avaliar a atividade da doença no lúpus eritematoso sistêmico (LES). O volume plaquetário médio (VPM) foi recentemente estudado como um biomarcador inflamatório. Atualmente não está claro se o VPM também pode desempenhar um papel como um biomarcador da atividade da doença em pacientes adultos com LES. Objetivo: Investigou-se a associação entre o VPM e a atividade da doença em pacientes adultos com LES. Métodos: Neste estudo retrospectivo, compararam-se dois grupos de pacientes adultos divididos de acordo com a atividade da doença (36 por grupo). Os indivíduos foram pareados por idade e gênero. Resultados: O VPM esteve significativamente diminuído nos pacientes com doença ativa em comparação com os níveis em pacientes com doença inativa (7,16 ± 1,39 versus 8,16 ± 1,50, p = 0,005). Em um nível de corte de 8,32 fL, o VPM tem uma sensibilidade de 86% e uma especificidade de 41% para a detecção da atividade da doença. Encontrou-se uma correlação positiva modesta entre o VPM e a albumina (r = 0,407, p = 0,001), que por sua vez está inversamente associada à atividade da doença. Conclusões: Em resumo, o VPM está diminuído em pacientes adultos com lúpus ativo e positivamente correlacionado com a albumina, outro biomarcador da atividade da doença. São necessários estudos prospectivos para avaliar o valor prognóstico desse biomarcador.

Evaluación de los valores séricos de prolactina en lupus eritematoso sistémico / Assessment of serum prolactin levels in patients with systemic lupus erythematosus

El propósito del presente estudio fue determinar la relación entre los valores de prolactina sérica y las características clínicas de pacientes con lupus eritematoso sistémico (LES) asistentes a la consulta de Reumatología del Servicio Autónomo Hospital Universitario de Maracaibo, en Maracaibo, Venezuela. Se realizó un estudio descriptivo, correlacional y transversal en pacientes femeninas, mayores de 18 años, con diagnóstico de LES, quienes asistieron al Hospital Universitario de Maracaibo, durante los meses de noviembre 2012 a junio del 2013; se les realizó una historia clínica integral, basada en anamnesis y examen físico, con énfasis en la búsqueda de manifestaciones clínicas de actividad lúpica y se tomaron muestras sanguíneas para la determinación de las concentraciones séricas de prolactina, en el momento de la evaluación de la paciente. Se utilizaron como rangos normales, valores entre 2,1 y 25 ng/mL. La población consistió en un total de 50 pacientes y se clasificó en dos grupos: el primer grupo conformado por 28 mujeres con crisis lúpica y el segundo por 22 sin crisis al momento del estudio. La concentración promedio de prolactina sérica fue de 39,0 ± 59,5 ng/dL para el primer grupo y de 14,2 ± 7,2 ng/dL para el segundo grupo, con diferencias estadísticamente significativas (p=0,044). Las pacientes con crisis lúpica presentaron valores de prolactina más elevados que las pacientes en remisión, no obstante que solo la séptima parte de ellas tenían cifras de prolactina fuera del rango normal. Todas las pacientes asintomáticas presentaron niveles normales de prolactina, por el contrario, todas las pacientes con hiperprolactinemia estaban en crisis lúpica.

To determine the relationship between hyperprolactinemia levels and clinical features of patients with systemic lupus erythematosus (SLE), a descriptive, correlational and cross-sectional study, was performed in female patients over 18 years old, who attended the Rheumatology Clinic at the Hospital Universitario, in Maracaibo, Venezuela, from November 2012 to June 2013. They underwent a comprehensive medical history evaluation, based on interviews and physical examination, with emphasis on the search for clinical manifestations of lupus activity. Blood samples were taken in order to determine prolactin levels at the moment of the patient evaluation. Values from 2.1 to 47.6 ng/mL were considered as normal. The population was classified into two groups: a group formed by 28 women with lupus crisis and another group formed by 22 patients without crisis. The average prolactin serum level was 39.0 ± 59.5 ng/dL for the first group and 14.2 ± 7.2 ng/dL for the second group, indicating statistical significance (p = 0.044). Patients with lupus crisis had prolactin values higher than those of asymptomatic patients, although only oneseventh of them had absolute hyperprolactinemia. All asymptomatic patients had normal levels of prolactin. All patients with hyperprolactinemia were in lupus crisis.

On lupus, vitamin D and leukopenia / Acerca de lúpus, vitamina D e leucopenia

Resumo Introdução A regulação imune está entre os efeitos não calcêmicos da vitamina D. Assim, essa vitamina pode influenciar em doenças autoimunes, como o lúpus eritematoso sistêmico (LES). Objetivos Estudar a prevalência da deficiência de vitamina D no LES e sua associação com o perfil clínico, sorológico e de tratamento, bem como com a atividade da doença. Métodos Mensuraram‐se os níveis séricos de OH‐vitamina D3 em 153 pacientes com LES e 85 controles. Os dados sobre o perfil clínico, sorológico e de tratamento de pacientes com lúpus foram obtidos por meio da revisão de prontuários. Simultaneamente à determinação da vitamina D, foi feito um hemograma e foi aplicado o Sledai (SLE disease activity índex [índice de atividade da doença no LES]). Resultados Os pacientes com LES tinham níveis mais baixos de vitamina D do que os controles (p = 0,03). Na análise univariada, a vitamina D sérica esteve associada à leucopenia (p = 0,02) e ao uso de ciclofosfamida (p = 0,007) e metotrexato (p = 0,03). Foi verificada uma correlação negativa com a dose de prednisona (p = 0,003). Não foi encontrada associação com a atividade da doença medida pelo Sledai (p = 0,88). Em um estudo de regressão múltipla, somente a leucopenia permaneceu como uma associação independente (B = 4,04; p = 0,02). Também foi encontrada correlação negativa do nível sérico de vitamina D com os granulócitos (p = 0,01), mas não com a contagem de linfócitos (p = 0,33). Conclusão Os pacientes com LES têm mais deficiência de vitamina D do que os controles. Essa deficiência não está associada com a atividade da doença, mas com a leucopenia (granulocitopenia).

Resumo Introdução A regulação imune está entre os efeitos não calcêmicos da vitamina D. Assim, essa vitamina pode influenciar em doenças autoimunes, como o lúpus eritematoso sistêmico (LES). Objetivos Estudar a prevalência da deficiência de vitamina D no LES e sua associação com o perfil clínico, sorológico e de tratamento, bem como com a atividade da doença. Métodos Mensuraram‐se os níveis séricos de OH‐vitamina D3 em 153 pacientes com LES e 85 controles. Os dados sobre o perfil clínico, sorológico e de tratamento de pacientes com lúpus foram obtidos por meio da revisão de prontuários. Simultaneamente à determinação da vitamina D, foi feito um hemograma e foi aplicado o Sledai (SLE disease activity índex [índice de atividade da doença no LES]). Resultados Os pacientes com LES tinham níveis mais baixos de vitamina D do que os controles (p = 0,03). Na análise univariada, a vitamina D sérica esteve associada à leucopenia (p = 0,02) e ao uso de ciclofosfamida (p = 0,007) e metotrexato (p = 0,03). Foi verificada uma correlação negativa com a dose de prednisona (p = 0,003). Não foi encontrada associação com a atividade da doença medida pelo Sledai (p = 0,88). Em um estudo de regressão múltipla, somente a leucopenia permaneceu como uma associação independente (B = 4,04; p = 0,02). Também foi encontrada correlação negativa do nível sérico de vitamina D com os granulócitos (p = 0,01), mas não com a contagem de linfócitos (p = 0,33). Conclusão Os pacientes com LES têm mais deficiência de vitamina D do que os controles. Essa deficiência não está associada com a atividade da doença, mas com a leucopenia (granulocitopenia).

Hormônio anti-Mülleriano como preditor de reserva ovariana em pacientes lúpicas: uma revisão / Anti-Müllerian hormone levels as a predictor of ovarian reserve in systemic lupus erythematosus patients: a review

RESUMOO hormônio anti-Mülleriano (HAM) é secretado a partir das células da granulosa dos folículos ovarianos em crescimento e parece ser o melhor marcador endócrino capaz de estimar a reserva ovariana. O lúpus eritematoso sistêmico (LES) é uma doença autoimune que acomete predominantemente mulheres em idade reprodutiva e pode afetar negativamente sua fertilidade pela atividade da doença, bem como pelos tratamentos usados. Conhecer o real impacto do LES e de seu tratamento na fertilidade vem sendo o objetivo de estudos recentes, os quais têm usado o HAM para esse fim.

ABSTRACTThe anti-Müllerian hormone (AMH) is secreted from granulosa cells of growing ovarian follicles and appears to be the best endocrine marker capable of estimating ovarian reserve. Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of reproductive age and may negatively affect their fertility due to disease activity and the treatments used. Recently, several studies assessed AMH levels to understand the real impact of SLE and its treatment on fertility.

Viabilidade da mensuração de marcadores de remodelação óssea em mulheres com lúpus eritematoso sistêmico / Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus

Objetivo: Investigar a viabilidade dos marcadores de remodelação óssea (MRO) na avaliação do metabolismo ósseo em pacientes com lúpus eritematoso sistêmico (LES), de acordo com as diretrizes da International Osteoporosis Foundation e da International Federation of Clinical Chemistry and Laboratory Medicine. Métodos: O estudo incluiu 43 pacientes do sexo feminino com LES. Foram medidos os níveis séricos de propeptídeo N-terminal do procolágeno tipo I (PINP), telopeptídeo C-terminal do colágeno tipo I (CTX), osteocalcina, HPT, 25(OH)D, anticorpos anticardiolipina, antidsDNA e antinucleossomo. Resultados: Os níveis de PINP e CTX estavam elevados em pacientes com LES com idade > 45, em comparação com aqueles com idade < 45 anos, embora com significância estatística limítrofe (p = 0,05). Foram encontradas correlações entre os MRO: a mais forte foi entre o PINP e a osteocalcina (τ = 0,69, p < 0,05). Encontrou-se que o PINP e a osteocalcina estão correlacionados com o HPT (τ = 0,3, τ = 0,29, respectivamente, p < 0,05). A idade estava correlacionada com o PINP (τ = 0,23, p < 0,05). Valores elevados de PINP foram encontrados em maior frequência do que valores elevados de osteocalcina ou CTX, tanto em pacientes com idade < 45 (p = 0,001) quanto > 45 (p < 0,001). Não houve diferença estatisticamente significativa nos níveis de PINP, osteocalcina ou CTX com relação à estação do ano, nem em todo o grupo de pacientes com LES, nem naqueles com mais ou menos de 45 anos. O uso prévio de glucocorticoides não esteve associado a diferenças nos MRO. Conclusões: O aumento nos MRO no LES parece refletir predominantemente o padrão de remodelação óssea relacionado com a idade. Pode-se esperar que o PINP aumentado seja o desfecho mais comumente encontrado entre os MRO. É necessário incluir melhores diagnósticos de distúrbios ósseos com MRO, feitos de acordo com as normas internacionais de referência, na abordagem de ...

Objective: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. Methods: The study included 43 female SLE patients. Serum pro-collagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. Results: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ= 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ= 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. Conclusions: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment. .

Leptina e adiponectina no lúpus eritematoso sistêmico: correlações clínicas e laboratoriais / Leptin and adiponectin in patients with systemic lupus erythematosus: clinical and laboratory correlations

Objetivo: Avaliar os níveis séricos de leptina e adiponectina em pacientes com lúpus eritematoso sistêmico (LES) e correlacionar seus níveis com atividade inflamatória, presença de autoanticorpos e manifestações clínicas. Métodos: Foram avaliadas 52 mulheres com LES e 33 mulheres saudáveis. As pacientes foram divididas em dois grupos, o primeiro com LES ativo e o segundo com LES inativo. Foram consideradas em atividade as paciente com Sledai ≥ 3. Os níveis séricos de leptina (ng/mL) e adiponectina (ug/mL) foram medidos por ensaio imunoenzimático. Resultados: Houve diferença significativa nos níveis de leptina entre LES e controle (20,7 ± 17,1 vs. 8,0 ± 5,0 ng/mL, p < 0,001), mas não houve diferença significativa nos níveis de adiponectina (87,5 ± 69,7 vs. 118,1 ± 70,6 ug/mL, p = 0,053). Entre LES inativo e ativo, não houve diferença significativa dos níveis de leptina e adiponectina. Houve uma associação significativa entre os baixos níveis de leptina e positividade para anticardiolipina (aCL) (p = 0,025) eanticoagulante lúpico (LA) (p = 0,003) e uma associação significativa entre níveis elevados deleptina e da presença de manifestação renal (p < 0,001). No entanto, não houve associaçãoentre adiponectina com autoanticorpos e características clínicas nas pacientes. Conclusão: Pacientes com LES apresentaram nível elevado de leptina, com associação aoenvolvimento renal. A leptina e a adiponectina não se correlacionaram com a atividade dadoença. Baixos níveis de leptina foram associados com a presença de LA e aCL. .

Objective: To evaluate the serum levels of leptin and adiponectin in patients with systemic lupus erythematosus (SLE) and correlate their levels with disease activity, presence of autoantibodies and clinical manifestations. Methods 52 women with SLE and 33 healthy women were evaluated. The patients were divided into two groups, the first with active SLE and the second with inactive SLE. Patients with SLEDAI ≥3 were considered active. Serum levels of leptin (ng/mL) and adiponectin (µg/mL) were measured by enzyme immunoassay. Results: There was a significant difference in leptin levels between SLE and controls (20.7 ± 17.1 vs. 8.0 ± 5.0 ng/mL, p < 0.001), but no significant difference in adiponectin levels (87 5 ± 69.7 vs. 118.1 ± 70.6 pg/mL, p = 0.053). No significant difference in levels of leptin and adiponectin was noted between inactive and active SLE groups. There was a significant association between low levels of leptin and positivity for anticardiolipin (aCL) (p = 0.025)and lupus anticoagulant (LA) (p = 0.003) and a significant association between high levelsof leptin and the presence of renal disease (p < 0.001). However, there was no association between adiponectin levels with autoantibodies and clinical features in SLE patients. Conclusion: Patients with SLE had elevated leptin levels, with association with renal involvement. Leptin and adiponectin were not correlated with disease activity. Low levels of leptin have been associated with the presence of LA and aCL. .

Rhupus syndrome

No abstract available.

Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with systemic lupus erythematosus

We evaluated the concentrations of 25-hydroxyvitamin D [25(OH)D] in children and adolescents with juvenile systemic lupus erythematosus (JSLE) and associated them with disease duration and activity, use of medication (chloroquine and glucocorticoids), vitamin D intake, calcium and alkaline phosphatase levels, and bone mineral density. Thirty patients with JSLE were evaluated and compared to 30 healthy individuals, who were age and gender matched. Assessment was performed of clinical status, disease activity, anthropometry, laboratory markers, and bone mineral density. The 30 patients included 25 (83.3%) females and 16 (53.3%) Caucasians, with a mean age of 13.7 years. The mean age at diagnosis was 10.5 years and mean disease duration was 3.4 years. Mean levels of calcium, albumin, and alkaline phosphatase were significantly lower in patients with JSLE compared with controls (P<0.001, P=0.006, and P<0.001, respectively). Twenty-nine patients (97%) and 23 controls (77%) had 25(OH)D concentrations lower than 32 ng/mL, with significant differences between them (P<0.001). Fifteen patients (50%) had vitamin D levels <20 ng/mL and 14 had vitamin D levels between 20 and 32 ng/mL. However, these values were not associated with greater disease activity, higher levels of parathormone, medication intake, or bone mineral density. Vitamin D concentrations were similar with regard to ethnic group, body mass index, height for age, and pubertal stage. Significantly more frequently than in controls, we observed insufficient serum concentrations of 25(OH)D in patients with JSLE; however, we did not observe any association with disease activity, higher levels of parathormone, lower levels of alkaline phosphatase, use of medications, or bone mineral density alterations.