Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Sorbonne Paris Cité, Université Paris Descartes, Faculté de Médecine-Site Broussais, Paris, France; Service de Médecine Interne, Centre de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France; Etablissement Français du Sang, Ile de France, Institut Mondor Recherche Biomédicale, Inserm U955, équipe 2, Université Paris-Est Créteil, Créteil, France.
Service de Médecine Interne, Centre de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France; Etablissement Français du Sang, Ile de France, Institut Mondor Recherche Biomédicale, Inserm U955, équipe 2, Université Paris-Est Créteil, Créteil, France.
J Autoimmun. 2015 Aug;62:22-30. doi: 10.1016/j.jaut.2015.05.006. Epub 2015 Jun 23.
Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood of newly diagnosed wAIHA patients and, accordingly, active germinal center reactions were present in the spleen of patients receiving short-term corticosteroid therapy. Long-term corticosteroid regimens markedly reduced this response while splenic plasma cells were able to persist, a fraction of them secreting anti-red blood cell IgG in vitro. In wAIHA patients treated by rituximab and who underwent splenectomy because of treatment failure, plasma cells were still present in the spleen, some of them being autoreactive. By using a set of diagnostic genes that allowed us to assess the plasma cell maturation stage, we observed that these cells displayed a long-lived program, differing from the one of plasma cells from healthy donors or from wAIHA patients with various immunosuppressant treatments, and more similar to the one of normal long-lived bone-marrow plasma cells. Interestingly, an increased level of B-cell activating factor (BAFF) was observed in the supernatant of spleen cell cultures from such rituximab-treated wAIHA patients. These results suggest, in line with our previous report on primary immune thrombocytopenia, that the B-cell depletion induced by rituximab promoted a suitable environment for the maturation and survival of auto-immune long-lived plasma cells in the spleen.
原发性温抗体自身免疫性溶血性贫血（wAIHA）是一种罕见的自身免疫性疾病，其中红细胞被 IgG 自身抗体清除。我们分析了不同治疗背景下 wAIHA 患者脾脏和外周血中的抗体分泌细胞。新诊断的 wAIHA 患者外周血中观察到浆母细胞，因此接受短期皮质类固醇治疗的患者脾脏中存在活跃的生发中心反应。长期皮质类固醇方案显著降低了这种反应，而脾浆细胞能够持续存在，其中一部分能够在体外分泌抗红细胞 IgG。在接受利妥昔单抗治疗且因治疗失败而行脾切除术的 wAIHA 患者中，脾脏中仍存在浆细胞，其中一些是自身反应性的。通过使用一组诊断基因，我们能够评估浆细胞的成熟阶段，观察到这些细胞表现出一种长寿的程序，与健康供体或接受各种免疫抑制剂治疗的 wAIHA 患者的浆细胞不同，更类似于正常长寿骨髓浆细胞的程序。有趣的是，从接受利妥昔单抗治疗的 wAIHA 患者的脾细胞培养物上清液中观察到 B 细胞激活因子（BAFF）水平升高。这些结果表明，与我们之前关于原发性免疫性血小板减少症的报告一致，利妥昔单抗诱导的 B 细胞耗竭促进了自身免疫性长寿浆细胞在脾脏中的成熟和存活的适宜环境。
