Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis Brazilian patients.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value = 0.0026, OR 1.31 and p value = 0.0091, OR 1.28 with statistical power = 0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (-3.3 fold) and monocytes (-3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA.

SIRT1 promoter polymorphisms as clinical modifiers on systemic lupus erythematosus.

Silent mating type Information Regulator 2 homolog 1 (SIRT1) is a deacetylase protein that participates in several physiological processes with importance in transcriptional silencing, apoptosis, immune system regulation and inflammation. Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease in which upregulated expression of SIRT1 on CD4+ T lymphocytes of active patients has been reported. Also, global hypoacetylation of histones H3 and H4, with H3 hypoacetylation was correlated with a higher disease activity index. SIRT1 promoter rs12778366 and rs3758391 may account for differential expression of this molecule and the role of these variants was investigated in SLE susceptibility and morbidity. Genomic DNA was extracted from peripheral blood of 367 SLE patients and 290 healthy controls of a Southern Brazilian population. SIRT1 rs12778366 and rs3758391 were amplified through PCR and genotyped through sequencing. No statistically significant differences were observed between patients and controls for allelic, genotypic or haplotypic frequencies. Nevertheless, SIRT1 rs3758391 was not in Hardy-Weinberg equilibrium, presenting a paucity of CT heterozygous both in patients and controls. SLE patients with TT and CT genotypes displayed a higher chance of developing lupus nephritis (Pc = 0.012, OR = 2.04 95 % CI 1.32-3.14) and presented a higher disease activity index (Mean rank 170.95 vs 137.26, Pc = 0.006) when compared with CC homozygous patients. Our results suggest that SIRT1 rs3758391 modifies SLE morbidity, with rs3758391 T allele being a risk factor for nephritis and a higher SLEDAI. Nevertheless, it remains to be elucidated how SIRT1 rs3758391 functionally influences SLE severity.

Genetic polymorphisms of glutathione S-transferases and cytochrome P450 enzymes as susceptibility factors to systemic lupus erythematosus in southern Brazilian patients.

Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease that presents several clinical manifestations, affecting multiple organs and systems. Immunological, environmental, hormonal and genetic factors may contribute to disease. Genes and proteins involved in metabolism and detoxification of xenobiotics are often used as susceptibility markers to diseases with environmental risk factors. Cytochrome P450 (CYP) enzymes activate the xenobiotic making it more reactive, while the Glutathione S-transferases (GST) enzymes conjugate the reduced glutathione with electrophilic compounds, facilitating the toxic products excretion. CYP and GST polymorphisms can alter the expression and catalytic activity of enzymes. This study aimed to investigate the role of genetic variants of CYP and GST in susceptibility and clinical expression of SLE, through the analysis of GSTM1 null, GSTT1 null, GSTP1*Ile105Val, CYP1A1*2C and CYP2E1*5B polymorphisms. 371 SLE patients from Hospital de Clínicas de Porto Alegre and 522 healthy blood donors from southern Brazil were evaluated. GSTP1 and CYP variants were genotyped using PCR-RFLP and GSTT1 and GSTM1 variants were analyzed by multiplex PCR. Among European-derived individuals, a lower frequency of GSTP1*Val heterozygous genotypes was found in SLE patients when compared to controls (p = 0.005). In African-derived SLE patients, the CYP2E1*5B allelic frequency was higher in relation to controls (p = 0.054). We did not observe any clinical implication of the CYP and GST polymorphisms in patients with SLE. Our data suggest a protective role of the GSTP1*Ile/Val heterozygous genotype against the SLE in European-derived and a possible influence of the CYP2E1*5B allele in SLE susceptibility among African-derived individuals.

Combined effects of CXCL8 and CXCR2 gene polymorphisms on susceptibility to systemic sclerosis.

UNLABELLED: A previous study suggested that the CXCR2 (+1208) TT genotype was associated with increased risk of systemic sclerosis (SSc). In the present study, we investigated the influence of variation in the CXCL8 and CXCR2 genes on susceptibility to SSc and combined the variant alleles of these genes to analyze their effects on SSc. METHODS: One fifty one patients with SSc and 147 healthy bone marrow donors were enrolled in a case-control study. Blood was collected for DNA extraction; typing of CXCL8 (-251) T/A and CXCR2 (+1208) T/C genes was made by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by agarose gel electrophoresis. RESULTS: The CXCR2-TC genotype was significantly less frequent in patients (23.8% versus 55.1% in controls; P<0.001, OR=0.26, 95%CI=0.15-0.43), whereas the CXCR2-CC genotype was significantly more frequent (44.4% versus 22.4% in controls; P<0.001, OR=2.76, 95%CI, 1.62-4.72). When CXCR2 and CXCL8 combinations were analyzed, the presence of CXCR2 T in the absence of CXCL8 A (CXCR2 T+/CXCL8 A-) was more frequent in patients than in controls (34.5% versus 3.5%; P<0.001, OR=14.50, 95%CI=5.04-41.40). However, CXCR2 TT and CXCL8 A were significantly more common in controls (100%) than in patients (58.3%) (P<0.001). Likewise, the presence of CXCR2 TC and CXCL8 A was more frequent in controls (95.1%) than in patients (75%) (P=0.004). Furthermore, the CXCR2-CC genotype in CXCL8 A was more frequent in patients (59.7% versus 0% in controls; P<0.001, adjusted OR=98.67, 95%CI=6.04-1610.8). In patients, a high frequency was observed in combination with the CXCL8 TA and AA genotypes (P<0.001; OR=28.92), whereas in controls, there was a high frequency of combination with CXCL8 T (P<0.001; OR=0.03) and TT (P<0.001; OR=0.01). CONCLUSIONS: These findings suggest a protective role of CXCL8 (-251) A in the CXCR2 (+1208) TT and TC genotypes and an increased risk of CXCL8 (-251) A in association with the CXCR2 (+1208) CC genotype in SSc patients.

Diminished expression of complement regulatory proteins on peripheral blood cells from systemic lupus erythematosus patients.

CD55, CD59, CD46, and CD35 are proteins with complement regulatory (Creg) properties that ensure cell and tissue integrity when this system is activated. The aim of this study was to evaluate the Creg expression on peripheral blood cells from SLE patients and its association with cytopenia and disease activity. Flow cytometric analyses were performed on blood cells from 100 SLE patients and 61 healthy controls. Compared with healthy controls, we observed in SLE patients with lymphopenia and neutropenia decreased expression of CD55, CD59, and CD46 (P < 0.05). In SLE patients with anemia, CD59 and CD35 were decreased on red blood cells. Furthermore, there was a negative correlation between CD55 and CD59 on neutrophils and the disease activity. The results suggest there is an altered pattern of Creg expression on the peripheral blood cells of SLE patients, and the expression is correlated with disease activity and/or with activation of the complement system.

Clinical diagnostic performance of different methods for the detection of antibodies to extractable nuclear antigens in connective tissue diseases: a cohort study.

BACKGROUND: Different methods for anti-ENA identification have been used. This can lead to confusion regarding the interpretation of the test results in clinical practice. Some studies have reported differences in sensitivity and specificity, but few compare clinical outcomes. Based on that, our aim was to compare the performance characteristics of various methods commonly used to detect anti-ENA antibodies in the sera of patients suspected to have connective tissue diseases (CTDs). METHODS: 189 patients with orders for anti-ENA were analyzed. Three common methods were used: DID, ELISA, and HA. Sensitivity, specificity, PPV, NPV, and LR were calculated using CTDs as the reference standard. RESULTS: 69.3% of the patients had a CTD and 32.8% had SLE. Sensitivity and specificity, respectively, according to the technique were: ELISA (50.0% - 78.9%); DID (31.3% - 89.5%); HA (40.9% - 87.7%). PPV were: 88.5% (HA), 87.2% (DID) and 84.6% (ELISA), and NPV were: 40.5% (ELISA), 39.1% (HA) and 36.2% (DID). CONCLUSIONS: Based on the very similar predictive test values, we believe that, at least in a moderate to high pretest probability, in our methodological scenario, there are no significant differences in the interpretation of test results when using ELISA, HA, and DID for anti-ENA detection.

Matrix metalloproteinase gene polymorphisms in patients with rheumatoid arthritis.

Several genetic factors seem to be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to analyze whether functional polymorphisms in the promoter region of the MMP-1, -3 and -9 genes were associated with RA. The study population comprises 110 RA patients and 100 healthy controls. The -1607 1G/2G MMP-1, -1171 5A/6A MMP-3, and -1562 C/T MMP-9 polymorphisms were analyzed. The frequency of the 5A allele of MMP-3 gene was significantly higher in the controls when compared with the RA patients (0.45 vs. 0.32, P < 0.01). No significant differences were observed in the allele frequencies for the MMP-1 and -9 polymorphisms between RA patients and controls. Individuals carrying MMP-3 5A allele have significant higher frequency of extra-articular manifestations and rheumatoid nodules than individuals homozygous for 6A allele (P < 0.05). The results presented in this study provide evidence of an association between the MMP-3 gene polymorphism and RA.

T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis.

The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p = .000053, OR = 2.35; p = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.

Treating psoriatic arthritis to target: discordance between physicians and patients' assessment, non-adherence, and restricted access to drugs precluded therapy escalation in a real-world cohort.

The treat-to-target strategy (T2T) was associated with better outcomes in psoriatic arthritis (PsA) compared to standard care in clinical trials. This study aimed to analyze factors precluding treatment optimization in a T2T strategy conducted in a real-world cohort of PsA patients. A retrospective cross-sectional study nested in a cohort was conducted. Medical records of patients ≥ 18 years old, fulfilling CASPAR criteria and with at least one visit in the PsA clinic, were reviewed. Demographic data, current medication, and minimal disease activity (MDA) criteria were recorded. Reasons for the non-escalation of therapy in patients who were not classified as MDA were reported as absolute and relative frequencies. In the 8-month period, 131 visits (corresponding to 74 patients) were conducted. The MDA criteria were available in 113 visits (86.3%) and patients were classified as MDA in 31.0% of the visits (N = 35/113). Although in 69.0% of the visits patients were not in MDA, (N = 78/113), therapy was adjusted in only 42.3% (N = 33/78). Reasons precluding treatment escalation in non-MDA subjects were physician's impression of remission (57.7%, N = 26), non-adherence to previous prescription (17.8%, N = 8), restricted access to drugs (17.8%, N = 8), adverse events (11.1%, N = 5), poor understanding of medication instructions (6.7%, N = 3), patient's refusal to escalate therapy (4.4%, N = 2), and recent change in therapy (2.2%, N = 1). Discordance between the physician's clinical evaluation and the MDA criteria, non-adherence to prescription, and poor access to drugs were the main factors precluding escalation of therapy in a T2T strategy in a real-world PsA cohort.

A pilot study of acupuncture as adjunctive treatment of rheumatoid arthritis.

We evaluated the efficacy of acupuncture as a useful adjuvant treatment in the management of rheumatoid arthritis (RA). A pilot, randomized, double-blind, and controlled clinical trial was conducted. Forty RA patients with active disease despite stable therapy for at least the preceding 1 month were randomized to receive a standard protocol of acupuncture (AC) or superficial acupuncture at non-acupuncture points (controlAC) for 9 weeks. The primary outcome was achievement of 20% improvement according to the American College of Rheumatology (ACR) 20 criteria after five and ten treatment sessions and after 1 month of follow-up. Secondary measures included Disease Assessment Scale (DAS), tender and swollen joint count, morning stiffness, Health Assessment Questionnaire (HAQ), visual analogue scale (VAS) of pain, physician global assessment of activity disease, physician and patient global assessment of treatment, and inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). There was not significant difference between the groups regarding the number of patients that reached ACR20 at the end of the treatment (p=0.479). However, after 1 month of follow-up, there was a trend in favor of the AC group, with p=0.068. Compared with the controlAC, the AC group also demonstrated significant improvement in the patient and physician global assessment of treatment and physician global assessment of disease activity, but there was no difference on other clinical and laboratorial measures. On the other hand, only the AC patients had within group improvement on the variables DAS, HAQ, morning stiffness, patient and physician global assessment of treatment, and physician global assessment of disease activity in comparison to baseline visit. Despite the improvement of some studied variables, there was no significant difference in the proportion of patients that reached ACR20 between the AC and controlAC groups. This negative result can be related to the small sample size, selection of patients, type of acupuncture protocol applied, and difficulties in establishing an innocuous and trustworthy placebo group to studies involving acupuncture.

The role of mannose-binding lectin in systemic lupus erythematosus.

Susceptibility to systemic lupus erythematosus (SLE) is associated with genetic, hormonal, immunological, and environmental factors. Many genes have been related with the appearance of SLE, including several loci that code different complement components and their receptors. Some genetic deficiencies of complement molecules are strongly associated with SLE, probably because these deficiencies could cause decreased clearance of apoptotic cell material. As a consequence of the apoptotic material accumulation, high levels of autoantigens can be presented inappropriately to the immune system in an inflammatory context, resulting in an imbalance on the mechanisms of immunological tolerance, immune system activation, and autoantibody production. Recent studies proposed a role to the mannose-binding lectin (MBL) in the SLE physiopathogenesis. This protein activates the complement system, and the presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations at the plasma levels of MBL. Some of these polymorphisms have been associated with SLE susceptibility, as well as with clinical and laboratory typical features of this disease, cardiovascular events, and infections. Besides, it has been described that the presence of anti-MBL autoantibodies in sera of SLE patients can influence MBL plasma levels and its functional activity.

[Rheumatoid arthritis and atherosclerosis]. / Artrite reumatóide e aterosclerose.

Rheumatoid arthritis is a systemic inflammatory autoimmune disease characterized by symmetric, erosive and chronic synovitis, especially of minor joints. It is associated with increased prevalence of cardiovascular disease and with high mortality. This occurs because of an accelerated atherogenic process, explained by traditional cardiovascular risk factors such as smoking, hypercholesterolemia, age, diabetes mellitus and systemic arterial hypertension. High levels of hemosedimentation velocity and C-reactive protein are directly correlated with increased cardiovascular events. Pro-inflammatory cytokines contribute with endothelial dysfunction, insulin resistance, dyslipidemia, prothrombotic effects and oxidative stress that are at the basis of the atherogenic process. Recent information about atherosclerosis in rheumatoid arthritis allows for identification of the risk factors involved in atherosclerosis that can be best controlled. This could result in a reduced manifestation of the process and its cutback, with consequent decrease of mortality and morbidity related to rheumatoid arthritis.

Survival analysis of patients with systemic lupus erythematosus in a tertiary hospital in southern Brazil.

Systemic lupus erythematosus (SLE) treatments progress over the years. However, the mortality remains higher than in the general population. Few studies have examined SLE patients' survival in Brazil. This study aims to identify the main characteristics and risk factors to predict mortality and recognize the main causes of death in Brazilian patients with SLE. We retrospectively assessed clinical, demographic, and serological characteristics from 600 patients followed since 2001 in SLE outpatient clinic from Hospital de Clínicas de Porto Alegre. Risk factors for mortality were examined by univariate and multivariate Cox proportional hazards regression analyses. A p < 0.05 was considered significant. There were 527 survivors (87.83%). The main causes of death were cardiovascular disease (17%), infection (17%), and infection and SLE activity (17%). Risk factors for death were age at diagnosis (HR 1.065, CI 95% 1.039-10.092), SLICC damage index (HR 1.299, CI 95% 1.076-1569), antiphospholip syndrome (HR 3.021, CI 95% 1.307-6.985), and metilprednisolone pulse (HR 2.628, CI 95% 1.283-5.383). Antimalarials was a protective factor for death (HR 0.191, CI 95% 0.064-0.570). Cardiovascular disease, infection, and SLE activity associated with infection were the main known causes of deaths in our SLE patients. Secondary antiphospolipid syndrome, highest score in SLICC damage index, advanced age at diagnosis, and high dose of corticosteroids were risk factors for mortality. Antimalarials was an important protective factor.

Age of onset influences on clinical and laboratory profile of patients with systemic lupus erythematosus.

The present study aims to evaluate differences in clinical and laboratory manifestations and medication use in the different ages of disease onset in patients with systemic lupus erythematosus (SLE). This cross-sectional study consisted of 598 SLE patients (550 female and 48 male), who attended the Rheumatology Clinic of the Hospital de Clínicas de Porto Alegre between 2003 and 2015. Demographic, clinical and laboratory data were collected. The patients were classified into three groups according to their ages at disease diagnosis. Mean age of diagnosis was 33.6 ± 14.3 years, and the median (25th-75th percentile) disease duration was 13 (7-20) years. Among the patients studied, 419 (70%) were adult-onset (aSLE), 90 (14.8%) were late-onset (lSLE) and 89 (14.8%) were childhood-onset (cSLE). The female to male ratio was higher in aSLE (18:1) compared to the other groups (p = 0.001). Arthritis was predominantly found in aSLE (78.5%) when compared with lSLE (57.7%) (p < 0.001). Nephritis was more common in cSLE (60.6%) than in lSLE (26.6%) (p < 0.001). Median (25th-75th percentile) of SLE disease activity index (SLEDAI) was higher in the cSLE group [2 (0-5)] when compared to the lSLE group [0 (0-4)] (p = 0.045). Childhood-onset SLE showed a more severe disease due to the higher incidence of nephritis and needed a more aggressive treatment with immunosuppressive drugs.

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

The 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.

Is ultrasound a better target than clinical disease activity scores in rheumatoid arthritis with fibromyalgia? A case-control study.

OBJECTIVES: Our goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM). METHODS: A matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM. Ultrasound (US) and clinical scoring were blinded for the presence of FM. Medians and proportions were compared by Mann-Whitney's test and McNemar's test, respectively. Spearman's rank correlation coefficients (rs) were calculated among clinical and US scores and differences were tested by r-to-z transformation test. RESULTS: Seventy-two women were included, out of 247 RA patients, mostly white, with median (IQR) age of 57.5 (49.3-66.8) years, with RA symptoms for 13.0 (6.0-19.0) years and FM symptoms for 6.0 (2.0-15.0) years. Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs and prednisone use was comparable between groups. Objective activity parameters were not different between groups. RA patients with FM had greater DAS28, SDAI and CDAI but similar GS-US7 and PD-US7. GS-US7 correlated with DAS28, SDAI and CDAI in patients with and without FM (rs = 0.36-0.57), while PD-US7 correlated with clinical scores only in patients without FM (rs = 0.35-0.38). CONCLUSION: To our knowledge, this is the first study to demonstrate that ultrasound synovitis scores are not affected by FM in RA patients. PD-US7 performed better than GS-US7 in long-standing RA patients with DAS28, SDAI or CDAI allegedly overestimated due to FM. Since sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients with FM.

Daily practice feasibility and effectiveness of treating long-standing rheumatoid arthritis to target with synthetic disease-modifying antirheumatic drugs: a prospective cohort study.

To prospectively study the daily practice feasibility and effectiveness of treat-to-target (T2T) strategy with synthetic drugs aiming to maintain and achieve disease remission or low activity based on DAS28 and CDAI in long-standing rheumatoid (RA) patients. Two hundred and forty-one consecutive RA patients from Hospital de Clínicas de Porto Alegre were followed for 14 (±5.3) months. At follow-up, patients were evaluated by a rheumatologist at least once every 3 to 4 months. Treatment was adjusted following a step-up strategy, based on the disease activity scores (DAS28 and CDAI), aiming at remission (<2.6 or <2.8, respectively) or at least low disease activity (<3.2 or <10). Patients were predominantly women (84.7 %), mean age 54.9 (±11.9) years with 11.1 (±7.4) years of disease duration. At visit 4, T2T intervention significantly reduced DAS28 (4.6 ± 1.6 vs. 4.0 ± 1.5; p < 0.005), CDAI [17.8 (8.2-28.7) vs. 12.6 (5.1-22.5); p < 0.001], and HAQ (1.5 ± 0.9 vs. 1.3 ± 0.8; p = 0.002). At the end of the study, compared to the baseline scores, more patients achieved remission by DAS28 (11.6 vs. 18.6 %; p < 0.001) and CDAI (8.1 vs. 13.6 %; p < 0.001) and also low disease activity by DAS28 (9.8 vs. 13.0 %; p < 0.001) and CDAI (23.9 vs. 28.4 %; p < 0.001). Both average doses of sulfasalazine and methotrexate at visit 4 were higher (1375 vs. 1621 mg, p = 0.024; and 14.5 vs. 16.5 mg, p < 0.001, respectively). More patients were on combination therapy at the end of the follow-up (48.2 vs. 52.3 %; p < 0.001). The implementation of T2T strategy in the treatment of RA was feasible and effective in this outpatient population. The optimization of synthetic DMARDs use with dose adjustments and combinations of drugs seemed to improve disease outcome regarding disease activity and functional status.

[Consensus of the Brazilian Society of Rheumatology for the diagnosis, management and treatment of lupus nephritis]. / Consenso da Sociedade Brasileira de Reumatologia para o diagnóstico, manejo e tratamento da nefrite lúpica.

OBJECTIVE: To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. METHOD: Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: 1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. 2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. 3) Risks and benefits of treatment should be shared with the patient and his/her family. 4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. 5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated). 7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including steroids and an immunosuppressive agent, even though histological confirmation is not possible. 8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient achieve and maintain a sustained and complete remission. 9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision.

Characteristics of NK cell activity in patients with systemic sclerosis.

INTRODUCTION: Previous studies have shown an increased expression of natural killer (NK) cells in the peripheral blood of patients with systemic sclerosis (SSc). NK cells are part of innate immunity, recognizing infected cells through killer immunoglobulin-like receptors (KIR), which show marked polymorphism. A novel model has been proposed predicting the activity of NK cells, evaluating whether there is excessive activation (EA), excessive inhibition (EI) or balance (B) (neutral). OBJECTIVE: To evaluate the activity of NK cells in patients with SSc and compare it with that of a control group. METHOD: This study comprised 110 patients with SSc and 115 healthy controls. A novel model that predicts the activity of NK cells was used. For that, cells with their respective KIR/HLA-C and Bw4 ligands were considered. The activity of NK cells was defined as EA, EI, or B. RESULTS: Our results showed that 63.5% of healthy controls had the KIR phenotype characterized by EI, as compared with 39.1% of the patients with SSc (P = 0.001). Considering only KIR2DL2-positive individuals, 34.7% of EI was found in healthy controls and 10.9% in patients with SSc (P < 0.001). CONCLUSION: In our study, the model that predicts the action of NK cells showed that healthy controls have higher frequency of EI as compared with SSc patients, suggesting a protective effect of the EI profile against the development of SSc. These results suggest a potential role of NK cells in the pathogenesis of SSc, but further studies should be conducted to confirm our data.

Assessing rheumatoid arthritis disease activity with ultrasound.

In practice, composite indices are used for rheumatoid arthritis (RA) disease activity evaluation. Despite valid and widely used, not rarely composite indices miss accuracy. Ultrasound (US) is more precise than clinical examination in synovitis appraisal. US-based disease activity estimation depends on the detection of synovitis. The most common synovitis abnormalities are proliferation, effusion, and neoangiogenesis. Gray scale ultrasound identifies synovial hypertrophy and effusion with its good soft tissue contrast. Additionally, power Doppler ultrasound depicts neoangiogenesis within synovia, remarking local inflammation. Several studies have combined local US findings to develop a patient level disease activity index. Most of them summed selected joint scores in an overall score of disease activity and evaluated its correlation with clinical composite indexes. To be incorporated into clinical practice, an overall US score must have some fundamental characteristics such as reproducibility, viability, and sensitivity to change over time. In global US score development, finding the joints that truly estimate individual disease activity is highly challenging. This article presents an up-to-date literature review on assessing RA disease activity with US and depicts the challenges in finding the perfect global US score.