Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab
Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab
复制标题
DOI：
10.1001/jamadermatol.2015.59
复制
发表时间：
2015-06-01
期刊：
影响因子：
10.9
通讯作者：
Maverakis, Emanual
中科院分区：
文献类型：
--
作者：
He, Yong;Shimoda, Michiko;Maverakis, Emanual
重要性免疫球伊加介导的疾病往往是难以管理，但迄今为止没有提出任何机制。利妥昔单抗是一种抗CD 20单克隆抗体，在治疗难治性粘膜类天疱疮中表现出良好的疗效。然而，并不是所有的粘膜类天疱疮病例对利妥昔单抗都有反应。在此，我们提出了一个治疗难治性粘膜类天疱疮的情况下，并提出了一个机制来解释缺乏反应therapy.OBSERVATIONS治疗前，直接免疫荧光检查活检样品从病人的病变周围皮肤表现出线性沉积的IgG和伊加沿着dermoepidermal交界。在包括利妥昔单抗在内的多药免疫抑制方案后，第二次活检的结果显示沿真皮表皮连接处仅存在伊加沿着。这一发现与来自同一患者的流式细胞术数据很好地相关，该数据表明尽管CD 20（+）细胞耗尽，但仍存在持续分泌IgA的浆母细胞/浆细胞群。此外，免疫组化分析的结果perilesional皮肤仍然是阳性的CD 19和CD 138免疫细胞（浆母细胞/浆细胞标记物）。结论和相关性这些研究结果表明，目前可用的免疫抑制药物，包括利妥昔单抗，不能消除IgA分泌浆母细胞/浆细胞，这可能是中央IgA介导的免疫球蛋白疾病的病理生理学。未来的研究需要开发替代的治疗策略，靶向自身反应性IgA分泌浆母细胞/浆细胞。
IMPORTANCE Immunobullous diseases mediated by IgA are often difficult to manage, but to date no mechanism has been proposed. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated good efficacy in the treatment of refractory mucous membrane pemphigoid. However, not all cases of mucous membrane pemphigoid respond to rituximab. Herein we present a case of treatment-refractory mucous membrane pemphigoid and propose a mechanism to explain the lack of response to therapy.OBSERVATIONS Before treatment, direct immunofluorescent examination of a biopsy sample from the patient's perilesional skin demonstrated linear deposition of IgG and IgA along the dermoepidermal junction. After a multidrug immunosuppressive regimen that included rituximab, results of a second biopsy demonstrated only IgA along the dermoepidermal junction. This finding correlated well with flow cytometry data from the same patient that demonstrated a persistent population of IgA-secreting plasmablasts/plasma cells, despite depletion of CD20(+) cells. In addition, results of immunohistochemical analysis of the perilesional skin remained positive for CD19 and CD138 immune cells (plasmablast/plasma cell markers).CONCLUSIONS AND RELEVANCE These findings suggest that current available immunosuppressive medications, including rituximab, cannot eliminate IgA-secreting plasmablasts/plasma cells, which are likely central to the pathophysiology of IgA-mediated immunobullous diseases. Future studies are needed to develop alternative therapeutic strategies that target autoreactive IgA-secreting plasmablasts/plasma cells.