The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis. Here, we identify cell-surface autoantigens using an expression cloning system. A cDNA library of endothelial cells is retrovirally transfected into a rat myeloma cell line from which AECA-positive clones are sorted with flow cytometry. Four distinct AECA-positive clones are isolated, and endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) are identified as endothelial autoantigens. Autoantibodies against EPCR and SR-BI are detected in 34.6% and 36.5% of cases, respectively, with minimal overlap (3.8%). Autoantibodies against EPCR are also detected in ulcerative colitis, the frequent comorbidity of TAK. In mechanistic studies, EPCR and SR-BI function as negative regulators of endothelial activation. EPCR has also an effect on human T cells and impair Th17 differentiation. Autoantibodies against EPCR and SR-BI block the functions of their targets, thereby promoting pro-inflammatory phenotype.

Objectives: The efficacy of avacopan as remission induction therapy for Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (AAV) is well-established. However, concerns regarding liver injury post-avacopan treatment remain, especially in Japan. Therefore, this study aimed to investigate drug-induced liver injury (DILI) associated with avacopan treatment. Methods: This study included 22 patients with AAV who were treated with avacopan at multiple centres in Japan between September 2021 and March 2024. DILI was assessed by the Japanese version of a revised electronic causality assessment method (RECAM-J 2023). Results: Among the 22 patients treated with avacopan, DILI was observed in nine cases (40.9%): six with microscopic polyangiitis and three with granulomatosis with polyangiitis. Severe DILI with elevated total bilirubin (T-Bil) was observed in four of the nine patients (44.4%), a few weeks after the initiation of avacopan therapy. Eight of the nine patients (88.9%) with DILI improved after discontinuation of avacopan and other medications, and one patient developed vanishing bile duct syndrome (VBDS) leading to death. Avacopan-induced DILI was classified into three patterns: 1, short-term injury without T-Bil elevation; 2, transient cholestatic liver injury with T-Bil elevation; 3, decompensated liver injury with marked T-Bil elevation (VBDS). The risk factors for severe DILI with T-Bil elevation in Japanese patients included older age, lower body mass index and early onset DILI following the initiation of avacopan treatment. Conclusion: Avacopan-induced DILI is relatively common in Japan and could be lethal. Frequent laboratory follow-ups should be considered, especially for elderly and low-body-weight patients.

Objective.: Although prednisolone (PSL) and immunosuppressants are key drugs for Takayasu arteritis (TA) treatment, there is limited evidence on the optimal PSL dose. The aim of this study was to investigate the correlation between the initial PSL dose and relapse in TA.Methods.: We enrolled 105 patients with TA who satisfied the criteria of the Japanese Circulation Society and American College of Rheumatology from 1990 to 2015. The clinical characteristics and outcomes of patients with TA were retrospectively evaluated. The relapse-free period was assessed according to the difference in initial treatments.Results.: Relapse was observed in 57 (59.4%) of 96 patients treated with immunosuppressive therapy at diagnosis during a median followup of 56 months. Male sex and younger age of onset were significantly associated with relapse. Although ≤ 30 mg/day PSL monotherapy was preferably prescribed for patients with lower inflammatory markers, compared with > 30 mg/day (87.2% vs 52.6%), a significantly higher relapse rate was observed in the ≤ 30 mg/day group (HR 1.78; p = 0.047). Further, the relapse-free period was longer in patients treated with ≥ 50 mg/day PSL compared with those treated with ≤ 40 mg/day PSL. Combination therapy improved the relapse-free period compared with PSL monotherapy in the short term. The initial PSL dose was not associated with adverse events.Conclusion.: A higher dose of PSL was associated with a significant decrease in the relapse rate. The effect of combination therapy on relapse needs to be further investigated. Lower-dose PSL monotherapy is an undesirable strategy for remission induction in TA, despite low disease activity.