Gavanescu Irina, Benoist Christophe, Mathis Diane
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13009-14. doi: 10.1073/pnas.0806874105. Epub 2008 Aug 28.
Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).
自身免疫调节因子（Aire）缺陷的小鼠和人类体内存在针对多种器官的循环自身抗体以及多器官自身炎症浸润。目前尚不清楚自身抗体或其来源B淋巴细胞在疾病的发生或进展中所必需的程度。我们在本研究中表明，Aire缺陷小鼠要出现暴发性浸润必须有B细胞存在。我们没有发现自身抗体直接致病的证据；相反，B细胞似乎在T细胞致敏或扩增中起着关键的早期作用。一种针对B细胞的治疗试剂利妥昔单抗可诱导Aire缺陷小鼠的自身免疫疾病缓解，这为将其应用于患有自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）的人类患者带来了希望。
