The overall mortality rate of patients with SSc was higher than that of the general population, probably because of poor prognostic factors including organ involvement. These factors should be carefully monitored during followup.

Granulomatosis with polyangiitis (Wegener's) is a rare autoimmune neutrophil-mediated vasculitis that can cause renal disease and mucosal manifestations. Antineutrophil cytoplasmic antibodies (ANCA) are present in many patients, vary in level over time, and induce neutrophil activation through engagement with Fc receptors (FcRs). Given roles for FcRs in ANCA-mediated neutrophil activation and IgA antibodies in mucosal immunity, we hypothesized that FcR genetics and previously unappreciated IgA ANCA affect clinical presentation. We assembled a total of 673 patients and 413 controls from two multicenter cohorts, performed ELISA and immunofluorescence assays to determine IgA and IgG ANCA positivity, and used Illumina, TaqMan, or Pyrosequencing to genotype eight haplotype-tagging SNPs in the IgA FcR ( FCAR ) and to determine NA1/NA2 genotype of FCGR3B, the most prevalent neutrophil IgG FcR. We evaluated neutrophil activation by measuring degranulation marker CD11b with flow cytometry or neutrophil extracellcular trap formation with confocal microscopy. Functional polymorphisms in FCGR3B and FCAR differed between patient groups stratified by renal involvement. IgA ANCA were found in ∼30% of patients and were less common in patients with severe renal disease. Neutrophil stimulation by IgA or IgG ANCA led to degranulation and neutrophil extracellcular trap formation in a FcR allele-specific manner (IgA:FCAR P = 0.008; IgG:FCGR3B P = 0.003). When stimulated with IgA and IgG ANCA together, IgG ANCA induced neutrophil activation was reduced ( P = 0.0001). FcR genotypes, IgA ANCA, and IgG ANCA are potential prognostic and therapeutic targets for understanding the pathogenesis and presentation of granulomatosis with polyangiitis (Wegener's).

BackgroundManifestations in neuropsychiatric systemic lupus erythematosus (NPSLE), especially active diffuse NPSLE syndromes, are some of the most difficult complications of the disease. For the evaluation and the diagnosis of central nervous system manifestations, including NPSLE, MRI is a very useful tool to detect the various abnormalities. However, the relationship between brain MRI findings and clinical variables has not yet been clarified in patients with diffuse NPSLE.ObjectivesThe aim of this study is to investigate the pathogenesis of diffuse NPSLE, by comparing various parameters such as serum autoantibodies and cytokines in cerebrospinal fluid (CSF) with abnormal findings revealed on brain MRIs in patients with diffuse NPSLE.MethodsFifty-three patients with diffuse NPSLE admitted to our University Hospital from 1992 to 2012 were exhaustively enrolled in this study. Their medical charts and brain MRI scans were reviewed. The relationship of MRI abnormalities with various parameters was analysed.ResultsAs many as 25 of 53 patients (47.2%) had abnormal MRI findings. MRI findings improved after treatment in 10 of 17 patients for whom follow-up studies were available. MRI abnormalities were not correlated with age at the onset of diffuse NPSLE. However, the disease duration of SLE was significantly longer in patients with abnormal MRI findings (p=0.0009). MRI abnormalities were not significantly associated with serum autoantibodies. However, there were significant elevations of the CSF protein level (p=0.0106) and the CSF interleukin 6 level (p=0.0225) in patients with abnormal MRI findings. Patients with MRI abnormalities showed significantly higher overall mortality (p=0.0348).ConclusionsThe results revealed that MRI abnormalities in diffuse NPSLE might be heterogeneous with regard to their reversibility. These data also indicate that patients with diffuse NPSLE and MRI abnormalities have more severe inflammation in the central nervous system related to the activity of diffuse NPSLE, as evidenced by poorer prognosis.

ObjectiveTo assess the utility of circulating adhesion molecule levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease.MethodsNinety-two Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicentre, observational study. Concentrations of intercellular adhesion molecule (ICAM) −1, E-selectin, L-selectin, and P-selectin in serum samples from all patients were measured by enzyme-linked immunosorbent asssay (ELISA). In 39 patients, adhesion molecule levels were measured each year for four years. The ability of baseline adhesion molecule levels to predict subsequent progression and severity in clinical and laboratory features were evaluated statistically.ResultsAt their first visit, serum levels of ICAM-1, E-selection, P-selectin were significantly elevated and serum L-selectin levels were significantly reduced in patients with SSc compared with healthy controls. Overall, serum ICAM-1 levels at each time point were significantly inversely associated with the %vital capacity (VC) of the same time and subsequent years by univariate analysis. The initial serum ICAM-1 levels were significantly inversely associated with the %VC at the fourth year by multiple regression analysis. The initial serum P-selectin levels were significantly associated with the health assessment questionnaire disability index (HAQ-DI) at the fourth year by multiple regression analysis. Initial adhesion molecule levels were not significantly associated with other clinical features including skin thickness score. Baseline adhesion molecule levels were not significantly associated with subsequent rate of change of clinical parameters.ConclusionIn patients with SSc, serum levels of ICAM-1 and P-selectin may serve as prognostic indicators of respiratory dysfunction and physical disability, respectively. Further longitudinal studies of larger populations are needed to confirm these findings.