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.

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.

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We clarified that the highest TMJA stage and a high value of HAQ-DI are novel important risk factors for moderate-to-severe SAS in RA patients.

Objectives To provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis. Methods PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach. Results For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively. Conclusion This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.