A past medical history of autoimmune disease predicts a future with fewer relapses in patients with ANCA-associated vasculitis.

OBJECTIVES: To explore the frequency and impact of an autoimmune disease past-medical history (PMH) in the clinical picture and outcomes of patients with antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV). METHODS: This was a retrospective study of patients with biopsy-proven AAV, >16 years old, with detailed information about their PMH. Outcomes of interest included remission, treatment resistance, relapse, end-stage kidney disease (ESKD), and death. RESULTS: 206 patients with biopsy-proven AAV and available information regarding their PMH were studied. 63(30.6%) of them had a history of autoimmune disease prior to AAV diagnosis. The mean age overall was 54.1 years. One hundred and five patients (51%) were positive for PR3-ANCA, 101 (49%) for MPO-ANCA. Granulomatosis with polyangiitis was diagnosed in 79 (38.3%), microscopic polyangiitis in 97 (47.1%) and renal-limited vasculitis in 30 (14.6%) individuals. Remission rate was similar among patients with and without a PMH of autoimmune disease. Time-to-event analysis indicated that the relapse-free survival was significantly longer in patients with PMH of autoimmune disease (148.2 vs. 61.9 months, p-value <0.001). After adjusting for covariates, autoimmune disease history was associated with significantly lower risk of relapse (HR: 0.33, 95% CI: 0.15-0.72), which remained significant in males, patients ≥60 years old and those with C/PR3-ANCA, kidney and lung involvement. CONCLUSIONS: Patients with a PMH of autoimmune disease, prior to AAV diagnosis, experienced significantly fewer relapses after achievement of remission, compared to patients without such a history, underlining the importance of individualisation of maintenance immunosuppressive therapy, given the different aetiopathogenetic settings the disease was developed.

Hypocomplementemia at Diagnosis of Pauci-immune Glomerulonephritis Is Associated With Advanced Histopathological Activity Index and High Probability of Treatment Resistance.

INTRODUCTION: Recent evidence suggests that complement activation is important in the pathogenesis of pauci-immune (PI) vasculitis. This is a retrospective investigation of the frequency of hypocomplementemia at pauci-immune glomerulonephritis (PIGN) diagnosis, in relation to vasculitic manifestations, renal histopathology, and treatment outcomes. METHODS: A total of 115 patients with biopsy-proven PIGN were categorized based on their serum complement C3 (sC3). Histopathology evaluation included activity and chronicity indexes. The primary outcome of interest was treatment resistance, defined as a progressive decline in kidney function, with persistently active urine sediment, leading to dialysis dependency or vasculitis-related death. RESULTS: In all, 20.9% of patients had low sC3 levels associated with more advanced renal impairment (P < 0.01), requiring acute dialysis (P < 0.01) more frequently compared to patients with normal sC3. Within 1 year, 85.7% of patients with normal sC3 responded to therapy, versus 58.3% of those with low sC3 (P = 0.001). The probability of treatment resistance was strongly associated with low sC3 (P = 0.004), high serum creatinine (P < 0.001), acute dialysis requirement (P < 0.001), and high histopathological score of chronicity (P < 0.01). Advanced histopathological activity was related to more intense interstitial leukocyte infiltration (P = 0.005) and higher likelihood of fibrinoid necrosis documentation in a vessel wall (P = 0.02). The probability of treatment resistance was higher in patients with low sC3 (odds ratio [OR] = 6.47, 95% confidence interval [CI] 1.47-28.35, P = 0.013), oliguria (OR = 29.57, 95% CI = 4.74-184, P < 0.0001), and high chronicity score (OR = 1.77, 95% CI = 1.23-2.54, P = 0.002). CONCLUSION: Low sC3 is emerging as an independent predictor of treatment resistance in patients with PIGN associated with higher index of histopathological activity at diagnosis compared to normal sC3.