B-cell depleting agents for ANCA vasculitides: A new therapeutic approach

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• 作者：José ; A. Gó ; mez-Puerta^a ; Luis F. Quintana^b ; John H. Stone^c ; Manuel Ramos-Casals^d ; Xavier Bosch^e ; ^{xavbosch@clinic.ub.es}
• 关键词：AAV ; ANCA-associated vasculitis ; ANCA ; anti-neutrophil cytoplasmic antibodies ; Breg ; regulatory B cells ; CRP ; C-reactive protein ; cPR3 ; PR3 complementary peptide ; CSS ; Churg&ndash ; Strauss syndrome ; CYC ; cyclophosphamide ; ESR ; erythrocyte sedimentation rat
• 刊名：Autoimmunity Reviews
• 出版年：2012
• 期刊代码：30_15689972
• 类别：med
• 出版时间：July, 2012
• 卷：11
• 期：9
• 页码：646-652
• 文件大小：532 K

摘要

Vasculitides associated with anti-neutrophil cytoplasmic antibody (ANCA) serum positivity affecting small and medium-sized vessels are defined as ANCA-associated vasculitis (AAV). Glomerulonephritis in AAV is characterized by focal necrosis, crescent formation, and few or no immunoglobulin deposits. In vitro and animal evidence suggests that ANCA play a pathogenic role in AAV. Specific gene expression signatures are reported to predict long-term prognosis in AAV, suggesting the possibility of individualizing therapy and identifying new therapeutic targets. Although immunosuppressants and glucocorticoids are the cornerstone of AAV therapy, results from two recent randomized controlled trials have shown the non-inferiority of rituximab, compared with cyclophosphamide, for the induction of remission in patients with severe AAV. In fact, in April 2011, the US Food and Drug Administration (FDA) approved rituximab, combined with glucocorticoids, as a front-line therapy for adult patients with granulomatosis with polyangiitis (GPA; Wegener's granulomatosis) or microscopic polyangiitis. This new indication for rituximab provided the first ever FDA-approved therapy for these two diseases and the first alternative to cyclophosphamide for the treatment of severe disease in almost 40 years. However, issues regarding the use of maintenance therapy after rituximab, the concurrent use of cyclophosphamide and the toxicity of rituximab remain unanswered and should be clarified in ongoing and future randomized controlled trials.