Myositis-specific and myositis-associated autoantibody profiles and their clinical associations in a large series of patients with polymyositis and dermatomyositis.

OBJECTIVE: To analyze the prevalence of myositis-specific and myositis-associated autoantibodies and their clinical correlations in a large series of patients with dermatomyositis/polymyositis. METHOD: This cross-sectional study enrolled 127 dermatomyositis cases and 95 polymyositis cases. The disease-related autoantibody profiles were determined using a commercially available blood testing kit. RESULTS: The prevalence of myositis-specific autoantibodies in all 222 patients was 34.4%, whereas myositis-associated autoantibodies were found in 41.4% of the patients. The most frequently found autoantibody was anti-Ro-52 (36.9%), followed by anti-Jo-1 (18.9%), anti-Mi-2 (8.1%), anti-Ku (4.1%), anti-SRP (3.2%), anti-PL-7 (3.2%), anti-PL-12 (2.7%), anti-PM/Scl75 (2.7%), and anti-PM/Scl100 (2.7%). The distributions of these autoantibodies were comparable between polymyositis and dermatomyositis, except for a higher prevalence of anti-Jo-1 in polymyositis. Anti-Mi-2 was more prevalent in dermatomyositis. Notably, in the multivariate analysis, anti-Mi-2 and anti-Ro-52 were associated with photosensitivity and pulmonary disorders, respectively, in dermatomyositis. Anti-Jo-1 was significantly correlated with pulmonary disorders in polymyositis. Moreover, anti-Ro-52 was associated with anti-Jo-1 in both diseases. No significant correlation was observed between the remaining autoantibodies and the clinical and/or laboratory findings. CONCLUSIONS: Our data are consistent with those from other published studies involving other populations, although certain findings warrant consideration. Anti-Ro-52 and anti-Jo-1 were strongly associated with one another. Anti-Ro-52 was correlated with pulmonary disorders in dermatomyositis, whereas anti-Jo-1 was correlated with pulmonary alterations in polymyositis.

EBV reactivation serological profile in primary Sjögren's syndrome: an underlying trigger of active articular involvement?

Antibody to Epstein-Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjögren's syndrome (pSS) were not established. We evaluated 100 pSS patients (American-European Criteria) and 89 age/gender/ethnicity-matched healthy controls. Disease activity was measured by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p = 0.501; 2.6 ± 1.1 vs. 2.5 ± 1.1 AU/mL, p = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p = 0.576; 141.3 ± 69.8 vs. 135.6 ± 67.5 RU/mL, p = 0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p < 0.0001; 38.6 ± 57.4 vs. 7.9 ± 26.3 RU/mL, p < 0.0001). Further analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed comparable age/gender/ethnicity (p ≥ 0.551), current prednisone dose (4.8 ± 6.9 vs. 5.1 ± 10.4 mg/day, p = 0.319), and current uses of prednisone (52.8 vs. 37.5 %, p = 0.148) and immunosuppressants (44.4 vs. 31.3 %, p = 0.201). ESSDAI values were comparable (p = 0.102), but joint activity was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid factor (p = 1.000), anti-α-fodrin (p = 0.390) or antiphospholipid antibodies (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.

Antibodies to ribosomal P proteins in lupus nephritis: a surrogate marker for a better renal survival?

OBJECTIVE: To define if antibodies to ribosomal P proteins disclose a better lupus nephritis long-term survival. METHODS: Sixty consecutive SLE patients with biopsy-proven nephritis (2004 ISN/RPS) were evaluated for renal survival parameters. Inclusion criteria were at least one serum sample at: renal flares, biopsy, and last follow-up until 2008. Anti-P was detected by ELISA/immunoblot and anti-dsDNA by indirect immunofluorescence/ELISA. RESULTS: Eleven patients (18%) with anti-P+ (without anti-dsDNA) during renal flare were compared to 49 (82%) persistently negative for anti-P throughout the study. At the final follow-up post-biopsy (6.3±2.5 vs. 6.8±2.4 years, p=0.36), the comparison of anti-P+/anti-dsDNA- with anti-P- group revealed a trend to lower mean creatinine levels (0.9±0.3 vs. 2.3±2.1 mg/dl, p=0.07), lower frequency of dialysis (0% vs. 35%, p=0.025), and higher frequency of normal renal function (91% vs. 53%, p=0.037). The overall renal survival was significantly higher in anti-P+/anti-dsDNA- compared to anti-P- (11.0±4.5 vs. 9.2±4.5 years, p=0.033), anti-dsDNA+/anti-P- (vs. 8.7±4.7 years, p=0.017), and anti-P-/anti-dsDNA- (vs. 9.8±4.3 years, p=0.09) groups. CONCLUSION: Our data supports the notion that anti-P antibody in the absence of anti-dsDNA during nephritis flares is a valuable marker to predict a better long-term renal outcome in lupus patients.

Antibodies to ribosomal P proteins: a potential serologic marker for lupus membranous glomerulonephritis.

OBJECTIVE: To evaluate the relevance of antibodies to ribosomal P proteins (anti-P antibodies) in discriminating histopathologic patterns of lupus nephritis. METHODS: The study group comprised 81 consecutive patients with systemic lupus erythematosus who underwent renal biopsy and for whom frozen serum was available at the time of biopsy. All biopsy specimens were reviewed in a blinded manner, according to the 2004 criteria of the International Society of Nephrology and the Renal Pathology Society. Anti-P antibodies were detected by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis, and anti-double-stranded DNA (anti-dsDNA) was detected by indirect immunofluorescence/ELISA. RESULTS: Anti-P antibodies were detected in 18 patients (22%). The demographic and clinical features of patients with and those without anti-P antibodies were similar. Remarkably, analyses of biopsy specimens revealed that the frequency of anti-P antibodies in patients with class V lupus nephritis was higher than the frequency among patients with other classes of renal disease (72% versus 28%; P = 0.005). Accordingly, anti-P antibody-positive patients had a higher mean (+/-SD) proteinuria level compared with anti-P antibody-negative patients (6.4 +/- 4.8 versus 4.7 +/- 3.9 gm/dl; P = 0.046). Renal function was preserved in 6 of 7 patients who had both isolated anti-P antibodies and class V lupus nephritis. In contrast, anti-dsDNA was associated with proliferative-class lupus nephritis (P = 0.050) and higher creatinine levels (P = 0.014). Furthermore, 7 of 9 patients with isolated anti-P antibodies had class V lupus nephritis, and, more importantly, 5 of these 7 patients (71%) displayed a pure membranous pattern. Conversely, a tendency toward the predominance of class V lupus nephritis (67%) with concomitant proliferative lesions was observed when anti-P antibody was associated with anti-dsDNA. CONCLUSION: Our data introduce anti-P antibody as a novel serologic marker for membranous lupus nephritis and support the notion that the presence of isolated anti-P antibodies may discriminate patients with pure class V lupus nephritis, whereas the simultaneous presence of anti-dsDNA antibodies suggests class V disease with concomitant proliferative lesions.

Síndrome do lúpus neonatal / Neonatal lupus syndrome

A síndrome do lúpus neonatal (SLN) é uma doenca auto-imune associada à presenca de auto-anticorpos na circulacão materno-fetal contra complexos ribonucléicos, SSA/Ro e SSB/La, e se caracteriza principalmente por bloqueio cardíaco congênito isolado (BCCI) e/ou manifestacões cutâneas e hematológicas. A despeito da sua raridade, a SLN é a principal causa de BCCI, sendo responsável pela importante mortalidade (20 por cento a 30 por cento) e morbidade desses pacientes. A denominacão de lúpus neonatal se baseia na semelhanca das lesões cutâneas associadas à SLN nos neonatos com aquelas observadas em pacientes com lúpus eritematoso sistêmico (SLE). Por outro lado, o termo "isolado", para designar o BCC na SLN, é utilizado para especificar a ausência de malformacões cardíacas congênitas e a ausência de infeccões que causam alteracões na conducão átrio-ventricular (BAV). A SLN constitui-se num clássico modelo de auto-imunidade adquirida, no qual os anticorpos IgG maternos atravessam a barreira placentária e na circulacão fetal podem exercer um papel importante na patogênese da síndrome. A presenca quase universal dos anticorpos anti-Ro/SSA e anti-SSB/La no soro materno e fetal os inclui como marcadores para a SLN. Ao contrário da lesão cardíaca que compromete irreversivelmente a conducão átrio-ventricular, os acometimentos cutâneos e/ou hematológicos são transitórios e podem regredir após o desaparecimento dos anticorpos maternos da circulacão do lactente. Clinicamente, a SLN representa um desafio para profissionais reumatologistas, obstetras, neonatalogistas, dermatologistas e cardiologistas pediátricos que têm como meta identificar o risco gestacional de desenvolvimento da doenca fetal, diagnosticar a síndrome precocemente e definir uma estratégia terapêutica adequada quando "in utero" ou pós-natal.