Data on exosomal-derived urinary miRNAs have identified several miRNAs associated with disease activity and fibrosis formation, but studies on prognosis are lacking. We conducted a qPCR array screening on urinary exosomes from 14 patients with biopsy-proven proliferative lupus glomerulonephritis with a renal outcome of clinical response (n = 7) and non-response (n = 7) following therapy. Validation studies were performed by qRT-PCR in a new lupus nephritis (LN) cohort (responders = 22 and non-responders = 21). Responder patients expressed significantly increased levels of miR-31, miR-107, and miR-135b-5p in urine and renal tissue compared to non-responders. MiR-135b exhibited the best predictive value to discriminate responder patients (area under the curve = 0.783). In vitro studies showed exosome-derived miR-31, miR-107, and miR-135b-5p expression to be mainly produced by tubular renal cells stimulated with inflammatory cytokines (e.g IL1, TNFα, IFNα and IL6). Uptake of urinary exosomes from responders by mesangial cells was superior compared to that from non-responders (90% vs. 50%, p < 0.0001). HIF1A was identified as a potential common target, and low protein levels were found in non-responder renal biopsies. HIF1A inhibition reduced mesangial proliferation and IL-8, CCL2, CCL3, and CXCL1 mesangial cell production and IL-6/VCAM-1 in endothelial cells. Urinary exosomal miR-135b-5p, miR-107, and miR-31 are promising novel markers for clinical outcomes, regulating LN renal recovery by HIF1A inhibition.

Objective.To analyze the role that infections play on the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) outcome.Methods.A retrospective study of adult patients with AAV diagnosed in a tertiary center. Clinical features, laboratory findings, treatment, relapses, major infections, and outcome were evaluated.Results.Included were 132 patients [51 microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), 29 eosinophilic GPA (EGPA)] with a mean followup of 140 (96–228) months. ANCA were positive in 85% of cases. A total of 300 major infections, mainly bacterial (85%), occurred in 60% patients during the followup. Lower respiratory tract (64%) and urinary tract infections (11%) were the most frequent, followed by bacteremia (10%). A total of 7.3% opportunistic infections were observed, most due to systemic mycosis. Up to 46% of all opportunistic infections took place in the first year of diagnosis, and 55% of them under cyclophosphamide (CYC) treatment. Bacterial infections were associated with Birmingham Vasculitis Activity Score (version 3) > 15 at the disease onset, a total cumulative CYC dose > 8.65 g, dialysis, and development of leukopenia during the followup. Leukopenia was the only factor independently related to opportunistic infections. Forty-four patients died, half from infection. Patients who had major infections had an increased mortality from any cause.Conclusion.Our results confirm that major infections are the main cause of death in patients with AAV.

Background Antibodies to M-type phospholipase A2 receptor (a-PLA2R) have been identified in most patients with idiopathic membranous nephropathy, but the prevalence in membranous lupus nephritis (MLN) is still unclear. The objective of this study was to assess the prevalence of a-PLA2R antibodies in a large cohort of patients with lupus nephritis. Methods a-PLA2R antibodies were measured by ELISA in serum from patients with systemic lupus erythematosus ( n = 190), of whom 37 had a biopsy-proven MLN. Positive samples were confirmed by commercial ELISA kit, Western blot and immunohistochemistry in renal tissue. Results A total of 10 from 190 patients (5.3%) with systemic lupus erythematosus had circulating a-PLA2R measured by in-house ELISA assay. The antibodies were detected in 7 patients with MLN (18.9%) and 3 patients with non-renal lupus disease (3.2%). PLA2R staining was detected in the kidney biopsy of 5 of the 7 (71.4%) patients with MLN. a-PLA2R levels were associated with active disease but not proteinuria levels. Presence of a-PLA2R antibodies at baseline was associated with worse remission rates and longer time to remission compared to those patients serologically negative. Conclusions a-PLA2R antibodies can be detected with low prevalence in MLN patients, but their detection is associated with a worse renal prognosis.