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ANCA-associated vasculitis (AAV) is a life-threatening disease characterized by small vessel inflammation and pathogenic self-directed antibodies. Programmed death-ligand 1 receptor (PD-1) and programmed cell death ligand-1 (PD-L1) are immune checkpoint molecules crucial for maintaining tolerance and immune homeostasis. After checkpoint inhibition therapy, development of various autoimmune diseases and immune-related adverse events (irAEs) have been observed. Here, we investigated the immunomodulatory roles of neutrophils through the expression of immune checkpoint molecule (PD-L1), migratory molecules (CXCR2), chemotactic chemokines (CXCL5) and other important molecules (BAFF and HMGB1) in development of AAV. We also scrutinized the immune mechanism responsible for development of pauci-immune crescentic GN (PICGN). We demonstrate for the first time that the frequency of PD-L1 expressing neutrophils was significantly reduced in AAV patients compared to healthy controls and correlated negatively with disease severity (BVASv3). Further, in renal biopsy, reduced PD-L1 immune checkpoint expression provides a microenvironment that unleashes uncontrolled activated CD4 + T cells, B cells, neutrophils and macrophages and ultimately causes engulfment of immune complexes leading to PICGN. Furthermore, during remission, reduced neutrophils PD-L1 and CXCR2 expression, increased neutrophils CXCL5 expression and increased peripheral effector memory T cells and increased HMGB1 and BAFF levels in serum, demonstrate the propensity for the persistence of sub-clinical inflammation, which could explain relapse, in this group of diseases. [ABSTRACT FROM AUTHOR]

The objective of the study is to report the outcomes of COVID-19 in ANCA-associated vasculitis (AAV) patients. This was a registry-based observational study conducted at a tertiary care center in north India. AAV patients with at least one follow-up visit between March 2020 and September 2021 were included. Demographic features, clinical manifestations, disease activity, and treatment details of underlying AAV were noted in all patients. Details of COVID-19 infection including severity, treatment, and outcomes were noted. Predictors of COVID-19 severity were determined using univariate analysis. A total of 33 (18.3%) out of 180 AAV patients contracted COVID-19 infection. Moderate COVID-19 infection was seen in 33.3% and severe or critical infection was seen in 36.3% of patients. Seventeen patients (51.5%) required supplemental oxygen therapy. Nine patients had active disease at the time of COVID-19 infection and three of them died due to COVID-19 infection. The risk of COVID-19 infection and its severity did not differ between patients receiving different immunosuppressants including rituximab induction. Hypothyroidism (p = 0.046) and ocular (p = 0.038) involvement due to AAV predicted the development of moderate to severe/critical COVID-19. Three (9.1%) patients died from COVID-19 and the rate of AAV flare after COVID-19 was similar to that in non-COVID-19 patients (15.3/100 person-year vs. 15.6/100 person-year, p = 0.95). Majority of the patients with AAV had moderate to severe or critical COVID-19 infection. The rate of death due to COVID-19 in AAV is higher than in general population. Use of standard remission induction regimens did not lead to increased risk of COVID-19 infection in our AAV cohort. [ABSTRACT FROM AUTHOR]

For the foreseeable future, vaccines are the cornerstone in the global campaign against the Coronavirus Disease-19 (COVID-19) pandemic. As the number and fatalities due to COVID-19 decline and the lockdown anywise rescinded, we recognize an increase in the incidence of autoimmune disease post-COVID-19 vaccination. However, the causality of the most vaccine-induced side effects is debatable and, at best, limited to a temporal correlation. We herein report a case of a 51-year-old gentleman who developed Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) 2 week post-COVID-19 vaccination. The patient responded favorably to oral steroids and rituximab. Additionally, we conducted a case-based review of vaccine-associated AAV describing their clinical manifestations and treatment response of this emerging entity. [ABSTRACT FROM AUTHOR]

Aim: To study the expression of B cell‐activating factor of tumor necrosis factor family (BAFF) and A proliferation‐inducing ligand (APRIL) genes in active and remitting patients with anti‐neutrophil cytoplasmic antibody‐associated vasculitis (AAV) and healthy controls and their correlation with disease activity. Methods: This was a prospective case‐control study. Gene expressions of BAFF and APRIL were studied in 32 patients with AAV (16 each with active disease and in remission) and 30 healthy age and sex matched controls by real‐time polymerase chain reaction. Results: Out of 32 AAV patients, 26 had granulomatosis with polyangiitis (GPA) and 6 had microscopic polyangiitis (MPA). Mean ages of patients in active (12 GPA and 4 MPA) and remission (14 GPA and 2 MPA) groups were 39.4 ± 17.2 and 44.6 ± 16.1 years, respectively. BAFF gene expression was significantly higher in both the active AAV group and remission AAV group compared to controls (P <.01). The BAFF expression was significantly higher in AAV patients in remission compared to active AAV patients (P =.003). In contrast, APRIL expression did not differ between AAV patients and controls (P =.829). However, APRIL had significantly higher expression in remission as compared to active patients (P =.048). There was no significant correlation of both BAFF and APRIL expression with disease activity markers (erythrocyte sedimentation rate, C‐reactive protein, platelets and Birmingham Vasculitis Activity Score version 3). Conclusion: BAFF gene is significantly expressed in patients with AAV. Among AAV patients, there is a significantly higher expression of BAFF and APRIL in remitting state of the disease as compared to active state. There is no significant change in APRIL gene expression in patients with AAV as compared to controls. This makes a case for anti‐BAFF therapy in future for AAV patients in northern India. [ABSTRACT FROM AUTHOR]

Objectives: To present single centre experience on the efficacy and safety of similar biologic of rituximab in patients with granulomatosis with polyangiitis (GPA). Methods: This was a retrospective study of GPA patients who received similar biologic of rituximab as either remission induction or maintenance agent. Demographic parameters, Birmingham Vasculitis Activity Score (BVAS-v3), vasculitis damage index, relapse and adverse events were retrieved from patient records. Outcomes noted were remission at 6 months in remission induction group and rates of relapses, adverse events, serious infections and mortality in both remission induction and maintenance groups. Results: Seventy-seven GPA patients were enrolled. Sixty received rituximab for induction and 57 for maintenance; 69% were anti PR-3 positive. In the induction group, median BVAS-v3 reduced from 12 (IQR 6–21.5) to 0 (0–1) at 6 months. At 6 months, 60% patients attained remission, 40% in primary induction group and 74% in re-induction group (p = 0.016%). In the maintenance group, seven (12%) patients had relapses with median time to relapse of 12 (6–22) months. Median relapse free survival was 21 (6–22) months on rituximab maintenance. There were 12 deaths (15.6%) and 18 serious infections. Conclusion: Similar biologic of rituximab was an effective agent for remission induction and remission maintenance in patients with GPA. Head to head trials with innovator molecule are needed to confirm these results. Key Points: • Remission was achieved in 60% of GPA patients who received similar biologic of rituximab as remission induction therapy. • Relapse rate during maintenance phase was 12% with similar biologic of rituximab. Serious infections and mortality with similar biologic of rituximab were comparable with that reported previously in AAV trials. [ABSTRACT FROM AUTHOR]

Rapidly progressive renal failure is a common but severe feature of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A histopathological classification for ANCA-associated pauci-immune glomerulonephritis was developed for prognostication of these patients. The present study aims to classify patients of pauci-immune glomerulonephritis according to this classification and its impact on outcome. Eighty-six subjects with pauci-immune glomerulonephritis between July 2006 and October 2012 were included in the study. Their renal biopsies were reviewed and classified into focal, crescentic, sclerotic and mixed class as per the new classification. The outcomes were analyzed after 6 months of treatment. Of the 86 subjects, 34 (39.53 %) were granulomatosis with polyangiitis, 36 (41.86 %) microscopic polyangiitis, 1 eosinophilic granulomatosis with polyangiitis, while the rest (17.44 %) were unclassifiable. Thirteen (15.5 %), 43 (51.2 %), 12 (14.3 %) and 16 (19 %) patients were classified as focal, crescentic, sclerotic and mixed class, respectively. The mean serum creatinine at baseline was 280.23, 659.46, 573.72 and 542.78 µmol/L in focal, crescentic, sclerotic and mixed class, respectively. The probability of improvement in renal functions at 6 months decreased from focal to crescentic to mixed to sclerotic class, while the probability of death was highest in the sclerotic class followed by the mixed class. This difference in outcome was maintained irrespective of the clinical diagnosis or the Birmingham Vasculitis Activity Score. Our study has shown that the histopathological classification can be used to predict the severity of renal dysfunction as well as the treatment outcomes in pauci-immune glomerulonephritis. [ABSTRACT FROM AUTHOR]