Koarada Syuichi, Tashiro Satoko, Suematsu Rie, Inoue Hisako, Ohta Akihide, Tada Yoshifumi
Division of Rheumatology, Saga University.
Nihon Rinsho Meneki Gakkai Kaishi. 2012;35(1):38-45. doi: 10.2177/jsci.35.38.
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease with multiple organ disorders. Although the prognosis of SLE has been recently improved, corticosteroid and immunosuppressive agents are still main treatment used in medical practice. Refractory disease and complications by the conventional drugs still remain. RP105 (CD180) is one of the toll-like receptor associated molecules. The molecule is expressed on mature B cells. Significantly increased population of RP105-negative [RP105(-)] B cells is found in SLE. RP105(-) B cells belong to highly activated and differentiated late B cells and produce autoantibodies including anti-dsDNA antibodies. RP105(-) B cells are further divided into at least 5 subsets that include novel human B cell subsets. In active SLE, subset 1 (activated B cells) and 3 (early-plasmablasts) are significantly increased compared to inactive SLE patients. Especially, subset 3 RP105(-) B cells may play an important role in pathophysiology of SLE. RP105(-) B cells from active SLE patients express preferentially BCMA (B-cell maturation antigen) compared to BAFF-R (B-cell activating factor-receptor) than normal subjects and other autoimmune diseases. In SLE, it is suggested that BAFF/APRIL (a proliferation-inducing ligand) maintain chronic activation and survival of RP105(-) B cells. The increased RP105(-) B cells may reflect the breaking of tolerance checkpoint for autoreactive B cells and finally affect autoimmunity in SLE. For the B cell therapy, especially targeting of autoantibody-producing B cells, including subset 3 of RP105(-) B cells, BCMA and RP105(-) B cell itself may be an ideal target.
系统性红斑狼疮（SLE）是一种具有多器官功能障碍的典型系统性自身免疫性疾病。尽管近年来SLE的预后有所改善，但糖皮质激素和免疫抑制剂仍是医学实践中的主要治疗手段。传统药物引起的难治性疾病和并发症仍然存在。RP105（CD180）是一种Toll样受体相关分子。该分子在成熟B细胞上表达。在SLE患者中发现RP105阴性[RP105(-)]B细胞的数量显著增加。RP105(-)B细胞属于高度活化和分化的晚期B细胞，可产生包括抗双链DNA抗体在内的自身抗体。RP105(-)B细胞进一步分为至少5个亚群，其中包括新型人类B细胞亚群。在活动期SLE中，与正常对照组相比，亚群1（活化B细胞）和亚群3（早期浆母细胞）显著增加。特别是，亚群3的RP105(-)B细胞可能在SLE的病理生理学中起重要作用。与正常受试者和其他自身免疫性疾病相比，活动期SLE患者的RP105(-)B细胞优先表达B细胞成熟抗原（BCMA）而非B细胞活化因子受体（BAFF-R）。在SLE中，有研究表明B细胞活化因子（BAFF）/增殖诱导配体（APRIL）可维持RP105(-)B细胞的慢性活化和存活。RP105(-)B细胞数量的增加可能反映了自身反应性B细胞耐受检查点的破坏，最终影响SLE中的自身免疫。对于B细胞治疗，特别是针对产生自身抗体的B细胞，包括RP105(-)B细胞的亚群3、BCMA和RP105(-)B细胞本身可能是理想的靶点。
