Depresión e inflamación: ¿Una relación más allá del azar? / Depression and inflammation: a relationship beyond random?

El tratamiento actual de la depresión mayor, una condición de alta prevalencia a nivel mundial, aún no resulta satisfactorio por las significativas tasas de falta de respuesta o de síntomas residuales. Esto, entre otras razones, ha motivado a la búsqueda de nuevos modelos de comprensión de los procesos biológicos que están a la base de esta enfermedad, con el propósito de encontrar mejores estrategias terapéuticas, al menos desde el punto de vista farmacológico. Se examinan algunas correspondencias entre los fenómenos clínicos y la articulación de los sistemas inmune, nervioso y endocrino, y se revisa algunas relaciones entre depresión y enfermedades inflamatorias sistémicas.

The current treatment of major depression, a condition of high prevalence worldwide, is still unsatisfactory due to the elevated rates of non-response or residual symptoms. This, among other reasons, has motivated the search for new models of understanding the biological processes that could better explain this disease, with the purpose of finding better therapeutic strategies, at least from the pharmacological point of view. Some correspondences between clinical phenomena and the interplay of the immune, nervous and endocrine systems are examined. Also, some relationships between depression and systemic inflammatory diseases are reviewed.

Dry eye in systemic lupus erythematosus patients / Olho seco em pacientes com lúpus eritematoso sistêmico

Abstract Objective: To study the association of dry eye with lupus disease activity and cumulative damage. To verify if epidemiological, treatment and autoantibody profile of SLE (systemic Lupus erythematosus) patients influence the presence of dry eye. Methods: We studied 70 SLE patients for the presence of dry eye by Schirmer test, disease activity by SLEDAI (SLE-Disease activity index) and cumulative damage by SLICC/ACR DI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). Patients were also submitted to the OSDI (Ocular Surface Disease Index) questionnaire. Epidemiological and treatment data and autoantibody profile were extracted from the charts. Results: Dry eye by Schirmer test was present in 51.4% of the sample. No association of the presence of dry eye with SLEDAI and SLICC DI were found (p = ns). Subjective symptoms of dry eye measured by OSDI showed a modest correlation with SLEDAI (Spearman rho = 0.32). Treatment profile did not influence in the presence of dry eye that was more common in older patients (p < 0.0001). Anti dsDNA had a negative association with the presence of positive Schirmer test (p = 0.0008). Conclusions: Dry eye detected by Schirmer test in SLE patients has no association with disease activity nor cumulative damage. Anti dsDNA seems to have a protective effect in this context.

Resumo Objetivos: Estudar a associação do olho seco com a atividade do lúpus eritematoso sistêmico (LES) e seus danos cumulativos. Verificar se o perfil epidemiológico, de tratamento e de auto anticorpos de pacientes com LES influencia a presença de olho seco. Métodos: Foram estudados 70 pacientes com LES para a presença de olho seco pelo teste de Schirmer, atividade da doença por SLEDAI (SLE Disease Activity Index) e dano cumulativo por SLICC/ACR DI (Clínicas Colaborativas Internacionais de Lúpus Eritematoso Sistêmico/American College of Rheumatology Damage Index). Os pacientes também foram submetidos ao questionário OSDI (índice de doenças da superfície ocular). Os dados epidemiológicos e de tratamento e o perfil de auto anticorpos foram extraídos dos prontuários. Resultados: Olho seco pelo teste de Schirmer esteve presente em 51,4% da amostra. Nenhuma associação da presença de olho seco com SLEDAI e SLICC/ACR DI foi encontrada (p = ns). Os sintomas subjetivos do olho seco medidos por OSDI mostraram uma correlação modesta com SLEDAI (Rho de Spearman = 0,32) . O perfil do tratamento não influenciou na presença de olho seco que era mais comum em uns pacientes mais idosos (p < 0, 1). Anti dsDNA teve uma associação negativa com a presença de teste positivo de Schirmer (p = 0, 8). Conclusões: Olho seco detectado pelo teste de Schirmer em pacientes com LES não tem associação com atividade da doença nem dano cumulativo. Anti dsDNA parece ter um efeito protetor neste contexto.

Células T reguladoras en lupus eritematoso generalizado / Regulatory T cells in systemic lupus erythematosus

Resumen El lupus eritematoso generalizado (LEG) es una enfermedad autoinmune crónica caracterizada por la pérdida de la tolerancia a los antígenos propios y la síntesis de diferentes autoanticuerpos con la formación y depósito de complejos inmunes y el daño de múltiples órganos. Las células T reguladoras (Treg) desempeñan un papel esencial en el mantenimiento de la tolerancia periférica, controlan el estado de activación del sistema inmune y limitan las respuestas autoinmunes. El estudio del número y la función de las diferentes subpoblaciones de células Treg en LEG ha sido objeto de una intensa investigación. Dependiendo del fenotipo de las células Treg analizado se ha reportado que la frecuencia de estas células en pacientes con LEG se encuentra disminuida, aumentada o sin alteraciones. Además, diferentes grupos han descrito que la función supresora de las células Treg de los pacientes con LEG se encuentra reducida o no se ve afectada. En conjunto, lo datos reportados sugieren que las células Treg desempeñan un papel relevante en la patogénesis del LEG y que estos linfocitos pueden ser considerados blancos potenciales para el diseño de nuevas estrategias terapéuticas para esta enfermedad.

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a loss of tolerance to self-antigens and synthesis of different autoantibodies, with the formation and deposition of immune complexes and damage to multiple organs. T regulatory cells (Tregs) play a crucial role in maintaining peripheral tolerance, controlling the state of activation of the immune system and limiting autoimmune responses. The study of the number and function of the different Treg cell subpopulations in SLE has been the subject of intense research. Depending on the analyzed Treg cell phenotype, the frequency of these cells has been reported to be reduced, increased or unaltered in patients with SLE. In addition, different groups have described that Treg cells suppressive function is reduced or unaffected in patients with SLE. Taken together, the reported data suggest that Treg cells play a relevant role in the pathogenesis of SLE and that these lymphocytes can be considered potential targets for the design of new therapeutic strategies for this condition.

Altered Tregs and oxidative stress in pregnancy associated lupus

Abstract Aim SLE is a systemic autoimmune disease generally affecting woman in the reproductive age. It is associated with an altered level of Tregs and oxidative stress while an increase in Tregs, and different antioxidant mechanisms to combat oxidative stress are essential for successful pregnancy. Hence, this study aims to determine the level of CD4+ and CD8+ Tregs and oxidative stress in pregnant lupus patients. Methods Ten healthy and 10 pregnant lupus volunteers from the North Indian population, within the age group of 20-30 years were enrolled in the study. All the patients were non-smokers, non-alcoholics and were not associated or undergoing therapy for any other disease. They had a SLEDAI of 37.4 ± 7.32 with 5.2 ± 1.93 years of disease duration. Oxidative stress was determined by measuring the enzyme activity of anti-oxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and the level of reduced glutathione and lipids peroxidised, spectrophotometrically. Flowcytometry was performed for immunophenotyping to determine CD8+ and CD4+ Tregs. Results Elevated CD8+ Tregs and diminished CD4+ Tregs were observed in pregnant lupus patients. Oxidative stress was significantly increased as the activities of anti-oxidant enzymes and level of reduced glutathione was considerably diminished. There was a substantial increase in the amount of lipids peroxidised. Conclusion Pregnant lupus patients undergo considerable level of oxidative stress in comparison to healthy pregnant woman. The decreased level of CD4+ Tregs and an increase in CD8+ Tregs might be another important factor responsible for pregnancy associated complications. Hence, lupus leads to alterations in the necessary conditions for a successful pregnancy, which might eventually cause higher mortality, morbidity and associated complications.

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.

O impacto do lúpus eritematoso sistêmico juvenil na inflamação gengival: achados clínicos, imunológicos e microbiológicos / The impact of juvenile systemic lupus erythematosus on gingival inflammation: clinical, immunological and microbiological findings

Os objetivos desse estudo foram avaliar a expressão de citocinas no soro e fluido gengival, a produção de arginina-peptidil-deiminase (anti-PPAD) e o perfil microbiológico de pacientes com lúpus eritematoso sistêmico juvenil (LESj) e comparar com indivíduos saudáveis sistemicamente. Como objetivo secundário, avaliamos o impacto do tratamento da inflamação gengival sobre a expressão das citocinas e dos níveis de anti-PPAD. Participaram do estudo 30 pacientes com LESj (idade média: 16,2 ± 1,5 anos) e 29 sem doença sistêmica (idade média 15,5 ± 2,3 anos), ambos com gengivite. Foram coletados dados reumatológicos, periodontais, sangue, fluido gengival e biofilme intrassulcular. As citocinas foram analisadas pelo multiensaio multiplex; anti-PPAD pelo ensaio de imunoabsorção enzimática (ELISA) e níveis bacterianos pelo checkerboard DNA-DNA hybridization. Para avaliar variáveis categóricas foi utilizado o teste Qui-quadrado de Pearson; para as numéricas, o teste U de Mann-Whitney e para as correlações a estatística tau-b de Kendall. No estudo longitudinal, foi utilizado o teste de McNemar para dados qualitativos, e o de Wilcoxon para dados numéricos. No estudo transversal, o grupo teste apresentou maiores níveis de profundidade de bolsa à sondagem (PBS), nível de inserção clínica (NIC), % de placa e sangramento do que o controle. Na análise do soro, G-CSF foi significativamente maior e TNF-α significativamente menor no grupo teste. Na análise do fluido gengival, IL-1ß, IL-7, IL-8, IL-13, G-CSF, IFN-γ e MCP-1 foram significativamente maiores e IL-4, IL-12(p70) e GM-CSF significativamente menores no grupo teste. Não houve diferença significativa nos níveis de anti-PPAD entre os grupos. S. constellatus, A. actinomycetencomytans, E. saburreum, V. parvula, S. intermedius, C. showae e F. nucleatum foram significantemente mais numerosas no grupo teste e A. gerencseriae e T. denticola no grupo controle. Após o tratamento da inflamação gengival, o SLEDAI, %NIC 1-2 e NIC reduziram significantemente. Já os valores de PBS e %NIC 0 aumentaram. No soro, houve diminuição significativa da IL-4 e IL-5 e aumento significativo dos níveis de anti-PPAD após o tratamento. Já no fluido gengival, houve diminuição significativa da IL-1ß, IL-10 e MCP-1 e aumento significativo da IL-4, IL-12(p70), IL-17, GM-CSF e INF-α. Sendo assim, podemos concluir que pacientes com LESj apresentaram piores condições periodontais, PBS, NIC, % de placa e sangramento do que pacientes saudáveis sistemicamente. A análise de citocinas mostrou um aumento do G-CSF e TNF-α no soro e de IL-1ß, IL-7, IL-8, IL-13, G-CSF, IFN-γ e MCP-1 no fluido gengival dos pacientes com LESj. Foram identificados anticorpos anti-PPAD nos pacientes com LESj, o que pode servir como gatilho para a quebra da tolerância imunológica. O estudo longitudinal intervencionista demonstrou que o tratamento da inflamação gengival melhorou significantemente os parâmetros %NIC 1-2 e NIC. Houve uma pequena, porém significante, piora na PBS, a qual acreditamos não ter relevância clínica. Observamos também uma melhora significante no SLEDAI e dos níveis de IL-4 e IL-5 no soro e um aumento das citocinas IL-12, IL-17 e GM-CSF no fluido gengival. Já em relação ao anticorpo anti-PPAD, observamos um aumento significativo após o tratamento da inflamação gengival.

The objectives of this study were to evaluate the expression of cytokines in serum and gingival fluid, the production of arginine-peptidyl-deiminase (anti-PPAD) and the microbiological profile of patients with juvenile systemic lupus erythematosus (jSLE) and compare with systemically healthy individuals. As a secondary objective, we evaluated the impact of treatment of gingival inflammation on cytokine expression and anti-PPAD levels. Thirty patients with jSLE (mean age: 16.2 ± 1.5 years) and 29 without systemic disease (mean age 15.5 ± 2.3 years), both with gingivitis, participated in the study. Rheumatological and periodontal data, blood, gingival fluid and intrassulcular biofilm were collected. Cytokines were analyzed by multiplex multi-assay; anti-PPAD by enzyme-linked immunosorbent assay (ELISA) and bacterial levels by checkerboard DNA-DNA hybridization. Pearson's Chi-square test was used to evaluate categorical variables; Mann-Whitney U test for numerical variables and Kendall's tau-b statistic for correlations. In longitudinal study, McNemar test was used for qualitative data, and Wilcoxon test for numerical data. In cross-sectional study, test group presented higher levels of probing depth (PD), clinical attachment level (CAL), % of plaque and bleeding than control group. In serum analysis, G-CSF were significantly higher and TNF-α significantly lower in test group. In analysis of gingival fluid, IL-1ß, IL-7, IL-8, IL-13, G-CSF, IFN-γ and MCP-1 were significantly higher and IL-4, IL-12(p70) and GM-CSF were significantly lower in test group. There was no significant difference in anti-PPAD levels between groups. S. constellatus, A. actinomycetencomytans, E. saburreum, V. parvula, S. intermedius, C. showae and F. nucleatum were significantly more numerous in test group and A. gerencseriae and T. denticola in control group. After treatment of gingival inflammation, SLEDAI, % CAL 1-2 and CAL decreased significantly. Already the values of PD and % CAL 0 increased. In serum, there was a significant decrease in IL-4 and IL-5 and a significant increase in anti-PPAD levels after treatment. In gingival fluid, there was a significant decrease in IL-1ß, IL-10 and MCP-1 and significant increase in IL-4, IL-12 (p70), IL-17, GM-CSF and INF-α. Thus, we can conclude that patients with jSLE presented worse periodontal conditions, PBS, NIC, % plaque and bleeding than systemically healthy patients. Cytokine analysis showed an increase in serum G-CSF and TNF-α and IL-1ß, IL-7, IL-8, IL-13, G-CSF, IFN-γ and MCP-1 in gingival fluid of patients with jSLE. Anti-PPAD antibodies have been identified in patients with jSLE, which may serve as a trigger for impaired immune tolerance. Longitudinal interventional study demonstrated that treatment of gingival inflammation significantly improved % CAL 1-2 and CAL parameters. There was a small, but significant worsening in PBS, which we believe has no clinical relevance. We also observed a significant improvement in SLEDAI and levels of IL-4 and IL-5 in serum and an increase in cytokines IL-12, IL-17 and GM-CSF in gingival fluid. Regarding the anti-PPAD antibody, we observed a significant increase after the treatment of gingival inflammation.

Immunometabolism and systemic lupus erythematosus / 北京大学学报(医学版)

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease, characterized by production of pathogenic autoantibodies and wide involvement of multiple systems. Damageofimmune tolerance and imbalance of immune homeostasis lead to the production of autoantibodies and the injuries of multiple organs and systems. In recent years, plenty of studies have identified that immunometabolism affects survival status of certain cells, also cell activation, differentiation and effector functions. Conversely, immune cells with different functions or differentiational status upregulate specific metabolic pathways to maintain their identities. In response to outer stimulations, naive immune cells differentiate into activated cells, accompanied with a series of immunometabolism changes. Therefore, abnormal immunometabolism can induce global imbalance of immune homeostasis, which further results in the initiation and development of autoimmune diseases, including SLE. Multiple abnormalities of immunometabolism have been found in patients with SLE or mouse models of lupus. Immune cells involved in the development of SLE, such as T cells, B cells, dendritic cells and macrophages present various metabolic abnormalities and pathological phenotypes. Among these cells, CD4+ T cells play predominant roles in the pathogenesis of SLE. Lots of studies demonstrated that CD4+ T cells and their subsets were in abnormal immunometabolic status,which further resulted in the development of SLE. In CD4+ T cells from patients with SLE or mouse models of lupus, both levels of glycolysis and oxidative phosphorylation are significantly higher compared with healthy controls. However,mitochondrial abnormalities, decreased ATP production and increased level of oxidative stress also have been found in these cells, which play important roles in the production of reactive oxygen intermediates and autoantibodies. Aggregated lipids rafts and increased synthesis of glycosphingolipid and cholesterol also have been observed in the CD4+ T cells from patients with SLE, leading to the abnormally elevated TCR signaling. Moreover, mechanistic target of rapamycin (mTOR) signaling is activated in the CD4+ T cells from both patients with SLE or mouse models of lupus and participate in the metabolic abnormalities of pathological CD4+ T cells. Progressive understanding of immunometabolism give us new insights of the pathogenesis of SLE and provide us with more therapeutic targets in the treatment of SLE.

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.

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus

Abstract: Background: The clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated. Objectives: This study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients. Methods: A hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test. Results: Forty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%). Study limitations: The sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias. Conclusions: The level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Characterization of inflammatory markers associated with systemic lupus erythematosus patients undergoing treatment / Caracterização de marcadores inflamatórios associados a pacientes com lúpus eritematoso sistêmico em tratamento

ABSTRACT Objective: To characterize the inflammatory profiles of patients with systemic lupus erythematosus receiving standard treatment compared to healthy controls. Patients and methods: Peripheral venous blood was collected from systemic lupus erythematosus patients (n = 14) and controls (n = 18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and Chemokine receptor CXCR2 expression surface antigen in neutrophils and lymphocytes, while cytokines were assayed in serum samples. Purified neutrophils were assayed by their ability to phagocytize human plasma-opsonized zymosan. Results: Patients had a median (interquartile range) disease activity index of 1.0 (0-2.0) characteristic of patients in remission. Interleukin-6 and interleukin-10 serum concentrations were significantly higher in the patient group compared to controls and the phagocytic index of circulating neutrophils was significantly reduced in patients compared to controls. The levels of interleukin-2, interleukin-5, interleukin-8 and tumor necrosis factor alpha did not significantly differ between patients and controls. Flow cytometric analysis revealed that the integrin expression levels were reduced in lymphocytes (but not in neutrophils) obtained from systemic lupus erythematosus patients, while surface expression of the chemokine receptor 2 was similar in both neutrophils and lymphocytes. Conclusion: Systemic lupus erythematosus patients receiving standard treatment presented with elevated systemic levels of interleukin-6 and interleukin-10, reduced neutrophil phagocytic capacity, and reduced lymphocyte expression of integrin even when symptoms were in remission. These alterations to innate immune components may put these individuals at a greater risk for acquiring infections.

RESUMO Objetivo: Caracterizar os perfis inflamatórios de pacientes com lúpus eritematoso sistêmico (LES) que recebiam o tratamento padrão em comparação com controles saudáveis. Pacientes e métodos: Coletou-se o sangue venoso periférico de pacientes com LES (n = 14) e controles (n = 18) no momento da entrada no estudo. As amostras de sangue foram usadas para quantificação, por citometria de fluxo, da expressão dos antígenos de superfície CD11b (integrina) e CXCR2 em neutrófilos e linfócitos, enquanto as citocinas foram avaliadas em amostras de soro. Avaliou-se a capacidade dos neutrófilos purificados de fagocitar zimosan opsonizado com plasma humano. Resultados: Os pacientes apresentavam uma pontuação mediana (intervalo interquartil) no Sledai de 1 (0-2), característica de pacientes em remissão. As concentrações séricas de IL-6 e IL-10 foram significativamente maiores no grupo de pacientes em comparação com os controles; o índice de fagocitose de neutrófilos circulantes estava significativamente reduzido nos pacientes em comparação com os controles. Os níveis de IL-2, IL-5, IL-8 e TNF-α não diferiram significativamente entre pacientes e controles. A análise da citometria de fluxo revelou que os níveis de expressão de CD11b estavam reduzidos nos linfócitos (mas não nos neutrófilos) obtidos de pacientes com LES, enquanto a expressão do receptor de superfície CXCR2 foi semelhante em neutrófilos e linfócitos. Conclusão: Os pacientes com LES que recebiam tratamento padrão apresentaram níveis sistêmicos elevados de IL-6 e IL-10, redução na capacidade fagocítica dos neutrófilos e redução da expressão de CD11b em linfócitos, mesmo quando os sintomas estavam em remissão. Essas alterações nos componentes da imunidade inata podem colocar esses indivíduos em maior risco de adquirir infecções.

Fc gamma receptor IIIa polymorphism is not associated with susceptibility to systemic lupus erythematosus in Brazilian patients / Polimorfismo do receptor Fc gama IIIa não está associado à susceptibilidade ao lúpus eritematoso sistêmico em pacientes brasileiros

ABSTRACT We evaluated the possible association between FCGR3A V/F (158) polymorphism and SLE susceptibility and clinical phenotype in 305 sequentially retrieved SLE patients and 300 healthy controls from the southeastern part of Brazil by allele-specific polymerase chain reaction. Our results showed no association between FCGR3A 158V/F alleles and susceptibility to SLE in this series of patients albeit the heterozygous genotype was strongly associated with the disease.

RESUMO Avaliou-se a possível associação entre o polimorfismo FCGR3A V/F (158) e a suscetibilidade e o fenótipo clínico do lúpus eritematoso sistêmico (LES) em 305 pacientes com LES admitidos sequencialmente e 300 controles saudáveis da Região Sudeste do Brasil por reação em cadeia da polimerase alelo-específica. Os resultados do presente estudo mostraram não haver associação entre os alelos FCGR3A 158 V/F e a suscetibilidade ao LES nessa série de pacientes, ainda que o genótipo heterozigoto tenha sido fortemente associado à doença.

Familial autoimmunity and polyautoimmunity in 60 Brazilian Midwest patients with systemic sclerosis / Autoimunidade familial e poliautoimunidade em 60 pacientes portadores de esclerose sistêmica da região Centro-Oeste do Brasil

ABSTRACT Introduction: Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of polyautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. Objectives: To describe the frequency of familial autoimmunity and polyautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. Methods: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS), as well as interviews of their relatives during the period from February 2013 to March 2014. Results: A frequency of 43.3% of polyautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with the presence of polyautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in polyautoimmunity patients were: Hashimoto's thyroiditis (53.8%), Sjögren's syndrome (38.5%), and inflammatory myopathy (11.5%). The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%), rheumatoid arthritis (22.6%), and SLE (22.6%). The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. Conclusions: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a continued vigilance and promptly diagnose other possible autoimmune disease in patients, or in their kin.

RESUMO Introdução: A esclerose sistêmica (ES) é uma enfermidade do tecido conjuntivo de etiologia desconhecida, caracterizada pela tríade de injúria vascular, autoimunidade e fibrose tecidual. Sabe-se que uma história familiar positiva representa o maior fator de risco já identificado para o desenvolvimento da ES em um determinado indivíduo. Observação prévia de alta prevalência de poliautoimunidade e de autoimunidade familiar em pacientes com ES reforça a ideia de que fenótipos autoimunes distintos podem dividir variantes comuns de susceptibilidade. Objetivos: Descrever a frequência de autoimunidade familiar e de poliautoimunidade em 60 pacientes com ES da região Centro-Oeste do Brasil, bem como relatar as principais doenças autoimunes observadas nessa associação de comorbidades. Métodos: Estudo transversal com recrutamento de 60 pacientes consecutivos, selecionados no Serviço de Reumatologia do Hospital Universitário da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul (FMUFMS), bem como entrevista de seus parentes, de fevereiro de 2013 a março de 2014. Resultados: Foi encontrada uma frequência de 43,3% de poliautoimunidade e de 51,7% de autoimunidade familiar nos pacientes com ES. Os pacientes com presença de poliautoimunidade e de autoimunidade familiar eram principalmente da forma difusa de ES, porém esse índice não atingiu significância estatística. As doenças autoimunes mais comumente observadas nos pacientes com poliautoimunidade foram: tireoidite de Hashimoto (53,8%), síndrome de Sjögren (38,5%) e miopatia inflamatória (11,5%). As principais doenças autoimunes observadas nos parentes dos pacientes com ES foram: tireoidite de Hashimoto (32,3%), artrite reumatoide (22,6%) e LES (22,6%). A presença de mais de uma enfermidade autoimune em pacientes com ES não se correlacionou com maior gravidade ou atividade da doença. Conclusões: A partir da alta prevalência encontrada de doenças autoimunes coexistentes em pacientes com ES, salientamos a importância do conceito de autoimunidade compartilhada, de forma a promover uma vigilância constante e diagnosticar prontamente uma possível outra doença autoimune nos pacientes ou em seus parentes.

Myelopathy in systemic lupus erythematosus: clinical, laboratory, radiological and progression findings in a cohort of 1,193 patients / Mielopatia no lúpus eritematoso sistêmico: achados clínicos, laboratoriais, radiológicos e evolutivos em uma coorte de 1. 193 pacientes

Abstract Objective To describe clinical, laboratory, radiological and progression characteristics of myelopathy in systemic lupus erythematosus (SLE). Patients and methods A retrospective analysis was performed on a cohort of 1193 patients with SLE (ACR criteria) in order to identify patients with myelopathy (neuropsychiatric ACR). Disease activity was assessed by the SLE activity index (SLEDAI) on the date of the event and functional capacity was assessed by the Expanded Disability Status Scale (EDSS) at the last visit. Results We identified 14 (1.2%) patients with myelopathy. All were women with a mean age of 30 ± 11.5 years. Myelopathy occurred at the diagnosis of SLE in four (28%) patients; and nine (64%) patients had another type of neuropsychiatric manifestation associated. Neurological recurrence was observed in one (7%) patient. Disease activity was observed in 2 (14%) patients. Cerebrospinal fluid presented pleocytosis on 7 (53%) patients; antiphospholipid antibodies were positive in 5 (45%). Magnetic resonance imaging (MRI) showed T2 hyperintensity with a predominance of longitudinal involvement in 6 (86%) patients. Most were treated with intravenous corticosteroids and cyclophosphamide. No patient had full recovery and four (36%) had high EDSS scores. Three (21%) patients died from sepsis early in the course of their myelopathy, during or after immunosuppressive therapy. Conclusions Myelopathy occurred in 14 (1.2%) of the patients in our cohort and this may be the first manifestation of the disease occurring independently of systemic disease activity. Although rare, myelopathy shows great morbidity and mortality, can be recurrent and MRI is critical for diagnosis.

Resumo Objetivo Descrever características clínicas, laboratoriais, radiológicas e evolutivas de mielopatia no lúpus eritematoso sistêmico (LES). Pacientes e métodos Foi feita análise retrospectiva de uma coorte de 1.193 pacientes com LES (critérios ACR) para identificar os pacientes com mielopatia (ACR neuropsiquiátrico). A atividade de doença foi analisada pelo Índice de Atividade do LES (Sledai) na data do evento e a capacidade funcional pela Escala Expandida do Estado de Incapacidade (EDSS) na última consulta. Resultados Foram identificados 14 (1,2%) pacientes com mielopatia. Todas eram mulheres com média de 30 anos (DP ± 11,5 anos). A mielopatia ocorreu no diagnóstico do LES em quatro (28%) e em nove (64%) havia outro tipo de manifestação neuropsiquiátrica associada. Recorrência do quadro neurológico foi observado em uma (7%) paciente. Atividade de doença foi observada em dois (14%) pacientes. O líquido cefalorraquidiano apresentava pleocitose em sete (53%) pacientes anticorpos antifosfolípides eram positivos em cinco (45%). A ressonância magnética (RM) demonstrou hipersinal em T2 com predomínio do comprometimento longitudinal em seis (86%) pacientes. A maioria foi tratada com corticosteroides e ciclofosfamida endovenosos. Nenhuma paciente teve completa recuperação e quatro (36%) tinham escores altos da EDSS. Óbito foi observado em três (21%) durante episódio de mielopatia, por septicemia durante ou após terapia imunossupressora. Conclusões A mielopatia ocorreu em 14 (1,2%) dos pacientes da nossa coorte e pode ser a primeira manifestação da doença e ocorrer independentemente de atividade sistêmica da doença. Embora rara, é de grande morbimortalidade, pode ser recorrente e a RM é fundamental para o diagnóstico.

Expression of BAFF and BR3 in patients with systemic lupus erythematosus

The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01). The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01). BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01). The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01). The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

Linfócitos Th17 e linfócitos T CD4+ multifuncionais em pacientes com lúpus eritematoso sistêmico / Th17 cells and CD4+ multifunctional T cells in patients with systemic lupus erythematosus

Resumo Introdução/Objetivo: Evidências recentes sugerem que anormalidades que envolvem os linfócitos Th17 estão associadas à fisiopatologia do lúpus eritematoso sistêmico (LES). Além disso, os linfócitos T multifuncionais (LTM), ou seja, aqueles que produzem múltiplas citocinas simultaneamente, estão presentes no meio inflamatório e podem estar implicados no processo autoimune observado no LES. No presente estudo, objetiva-se caracterizar o estado funcional dos linfócitos T CD4+ no LES e determinar simultaneamente a concentração de IL-2, IFN-γ e IL-17 em culturas de linfócitos sob estímulos exógenos e autoantigênicos. Pacientes e métodos: Dezoito pacientes com doença ativa, 18 com doença inativa e 14 controles saudáveis foram submetidos à análise do estado funcional dos linfócitos T CD4+. Resultados: Encontrou-se que os pacientes com LES apresentaram uma diminuição na quantidade total de células CD4+, um aumento na quantidade de linfócitos T ativados e um aumento na frequência de linfócitos Th17 em comparação com controles saudáveis (HC). As células LTM tinha frequência aumentada em pacientes com LES e houve um aumento na frequência de LTM trifuncionais em pacientes com LES ativo em comparação com aqueles com LES inativo. Curiosamente, as células MTF produziram quantidades maiores de IFN-γ do que os linfócitos T monofuncionais em pacientes e controles. Conclusão: Analisados em conjunto, esses dados indicam a participação dos linfócitos Th17 recentemente ativados e células MTF na fisiopatologia do LES.

Abstract Introduction/Objective: Recent evidence suggests that abnormalities involving Th17 lymphocytes are associated with the pathophysiology of systemic lupus erythematosus (SLE). In addition, multifunctional T cells (MFT), i. e., those producing multiple cytokines simultaneously, are present in the inflammatory milieu and may be implicated in the autoimmune process observed in SLE. In the present study, we aimed to characterize the functional status of CD4+ T cells in SLE by simultaneously determining the concentration of IL-2, IFN-γ and IL-17 in lymphocyte cultures under exogenous and self-antigenic stimuli. Patients and methods: Eighteen patients with active disease, 18 with inactive disease, and 14 healthy controls had functional status of CD4+ T cells analyzed. Results: We found that SLE patients presented a decreased number of total CD4+ cells, an increased number of activated T cells, and an increased frequency of Th17 cells compared to healthy controls (HC). MFT cells had increased frequency in SLE patients and there was an increased frequency of tri-functional MFT in patients with active SLE compared with those with inactive SLE. Interestingly, MTF cells produced larger amounts of IFNγ than mono-functional T cells in patients and controls. Conclusion: Taken together these data indicate the participation of recently activated Th17 cells and MTF cells in the SLE pathophysiology.

Associação de imunodeficiência primária com lúpus eritematoso sistêmico: revisão da literatura e as lições aprendidas pela Divisão de Reumatologia de um hospital universitário terciário em São Paulo / Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil

Resumo As imunodeficiências primárias (IDP) representam um grupo heterogêneo de doenças resultantes de defeitos hereditários no desenvolvimento, na maturação e na função normal de células do sistema imunológico; assim, tornam os indivíduos suscetíveis a infecções recorrentes, alergia, autoimunidade e doenças malignas. Neste estudo retrospectivo descrevem-se doenças autoimunes (DAI), em especial o lúpus eritematoso sistêmico (LES), que surgiram associadas ao curso das IDP. Classicamente, a literatura descreve três grupos de IDP associadas ao LES: (1) deficiência de componentes da via do complemento, (2) defeitos na síntese de imunoglobulinas e (3) doença granulomatosa crônica (DGC). Na atualidade, outras IDP têm sido descritas como manifestações clínicas do LES, como a síndrome de Wiskott-Aldrich (WAS), a poliendocrinopatia autoimune-candidíase-distrofia ectodérmica (APECED), a síndrome linfoproliferativa autoimune (ALPS) e a linfocitopenia idiopática CD4+. Também são apresentados achados de uma coorte de adultos do ambulatório da Divisão de Reumatologia da Universidade Federal de São Paulo. As manifestações de IDP encontradas pelo nosso grupo de estudo foram consideradas leves em termos de gravidade de infecções e mortalidade no início da vida. Assim, é possível que alguns estados de imunodeficiência sejam compatíveis com a sobrevivência em relação à suscetibilidade infecciosa; no entanto, esses estados podem representar um fator de predisposição forte para o desenvolvimento de doenças imunológicas, como observado no LES.

Abstract Primary immunodeficiency disorders (PID) represent a heterogeneous group of diseases resulting from inherited defects in the development, maturation and normal function of immune cells; thus, turning individuals susceptible to recurrent infections, allergy, autoimmunity, and malignancies. In this retrospective study, autoimmune diseases (AIDs), in special systemic lupus erythematosus (SLE) which arose associated to the course of PID, are described. Classically, the literature describes three groups of PID associated with SLE: (1) deficiency of Complement pathway components, (2) defects in immunoglobulin synthesis, and (3) chronic granulomatous disease (CGD). Currently, other PID have been described with clinical manifestation of SLE, such as Wiskott–Aldrich syndrome (WAS), autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS) and idiopathic CD4+ lymphocytopenia. Also we present findings from an adult cohort from the outpatient clinic of the Rheumatology Division of Universidade Federal de São Paulo. The PID manifestations found by our study group were considered mild in terms of severity of infections and mortality in early life. Thus, it is possible that some immunodeficiency states are compatible with survival regarding infectious susceptibility; however these states might represent a strong predisposing factor for the development of immune disorders like those observed in SLE.

Systemic lupus erythematosus and Raynaud's phenomenon

Abstract: BACKGROUND: Patients with systemic lupus erythematosus seem to belong to different serological and clinical subgroups of the disease. Genetic background can cause the appearance of these subgroups. OBJECTIVE: To determine whether Brazilian patients who have systemic lupus erythematosus and Raynaud's phenomenon differ from those who do not. METHODS: Retrospective analysis of 373 medical records of systemic lupus erythematosus patients studied for demographic, clinical and serological data. A comparative analysis was performed of individuals with and without RP. RESULTS: There was a positive association between Raynaud's phenomenon and age at diagnosis (p=0.02), presence of anti-Sm (p=0.01) antibodies and anti-RNP (p<0.0001). Furthermore, a negative association was found between Raynaud's phenomenon and hemolysis (p=0.01), serositis (p=0.01), glomerulonephritis (p=0.0004) and IgM aCL (p=0.004) antibodies. CONCLUSION: Raynaud's phenomenon patients appear to belong to a systemic lupus erythematosus subset with a spectrum of clinical manifestations located in a more benign pole of the disease.

Teleducation about Cleft Lip and Palate: An Interdisciplinary Approach in the Promotion of Health

Introduction The Young Doctor Project (YDP) uses Telehealth and Interactive Teleducation instruments to promote the integration of different areas of health and to build knowledge. This methodology can also foster public awareness on various issues related to health. In this context, the objective of this study was to emphasize cleft lip and palate (CLP), which is one of the most common birth defects in Brazil. Objective The study aimed to apply a model of education regarding CLP, based on the dynamics of the YDP, and to evaluate the participants' knowledge acquired after participating in the YDP. Methods The participants were 41 students, 13 to 15 years of age and at the eight- and ninth-grade levels in a private elementary school in Bauru (Brazil). To analyze the performance of the participants, a questionnaire was administered before and after the completion of the training program. The training program was structured in three steps using: (1) interactive teleducation classes, (2) a cybertutor, and (3) practical activities. Results There was a statistically significant difference between the pre- and postparticipation questionnaire results. The improved performance of participants is evidenced by the increase in the rate of correct answers on all issues. Conclusion The YDP on CLP was applied in the school setting following the three steps recommended by the project, and, after the implementation of the training program, there was a significant increase in participants' knowledge of CLP. The YDP on CLP proved an effective tool in promoting health education. .

Association between the presence of anti-c1q antibodies and active nephritis in patients with systemic lupus erythematosus

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). A retrospective analysis was carried out on a group of 24 patients with SLE to evaluate whether the presence of anti-C1q antibodies (anti-C1q) is related to renal involvement and to explore the behaviour of anti-C1q with respect to LN during a four-year follow-up period. A first serum sample stored at the serum bank, taken not more than three years after SLE diagnosis and one serum sample per year for the subsequent four years were used to detect anti-C1q. Lupus clinical manifestations and serological markers of activity corresponding to the date of each serum sample selected were collected from medical records. In the first serum sample, anti-C1q were found in 8 active SLE. LN was confirmed by histology in 5/8 patients who were positive for anti-C1q and in 1/16 patients who were negative for these autoantibodies (p = 0.0069). Three patients (3/8) had anti-C1q without renal involvement but with lupus skin manifestation. Anti-C1q levels decreased in 3/5 patients with LN who responded to treatment and remained higher in 2/5 patients who needed a new renal biopsy which showed severe renal disease. The 15 patients without severe kidney disease and anti-C1q negative at diagnosis did not develop LN and anti-C1q remained negative in the 4 years of follow up. Anti-C1q were found in SLE patients with active renal involvement or with lupus skin disease. The absence of anti-C1q seemed to be linked to low probabilities of renal involvement.

La nefritis lúpica (NL) es una complicación grave del Lupus Eritematoso Sistémico (LES). Se analizó retrospectivamente en 24 pacientes con LES si la presencia del anticuerpo anti-C1q (anti-C1q) se asociaba con NL y el comportamiento del anti-C1q respecto a la NL en un período de seguimiento de cuatro años. El anti-C1q se determinó en una primera muestra de suero no distante en más de tres años del diagnóstico de LES y en una muestra por año en los siguientes cuatro años. Se obtuvo información de las historias clínicas, sobre manifestaciones clínicas de LES y marcadores serológicos de actividad para las fechas de selección de cada suero. En la primera muestra de suero se detectó anti-C1q en 8 pacientes con LES activo. NL fue confirmada por histología en 5 de ellos y en uno de 16 pacientes con anti-C1q negativos (p = 0.0069); 3 de 8 pacientes fueron anti-C1q positivos sin NL y con lesiones en piel. Los niveles de anti-C1q disminuyeron en 3/5 pacientes con NL que respondieron al tratamiento y se mantuvieron aumentados en 2/5 que necesitaron una nueva biopsia, que evidenció compromiso renal grave. Los 15 pacientes sin enfermedad renal grave y con anti-C1q negativo al diagnóstico no desarrollaron NL y el anti-C1q se mantuvo negativo en los 4 años de seguimiento. El anti-C1q se asoció en pacientes con LES a NL activa o con compromiso en piel. La ausencia del anti-C1q parecería relacionarse a un menor riesgo de desarrollar nefropatía lúpica.