Immune cytopenias, such as autoimmune hemolytic anemia, immune thrombocytopenia, and Evans syndrome, are characterized by autoantibodies targeting various blood cells, initiating their destruction. Interactions between T cells, B cells, their ultimate maturational plasma cell descendants, dendritic cells, and macrophages result in antibody production, including the autoreactive ones. Autoimmune phenomena can be idiopathic or associated with various immune dysregulation conditions or malignancies. Interventions disrupting this complex network at different levels have been used to treat immune cytopenias with certain levels of success. Some cases are known to be refractory to many different therapeutic approaches, including the ones eliminating B cells. In some such cases, targeting plasma cells resulted in disease control. Among plasma cell compartments, unique long-lived plasma cells (LLPCs) residing primarily in the bone marrow, are specialized antibody-producing cells with an extended lifespan, capable of persistently secreting antibodies. LLPCs can evade conventional therapeutic strategies designed to target often-proliferating cells. Research focusing on the role of LLPCs in autoimmune phenomena including immune cytopenias has provided evidence for their role, characterized by the sustained production of autoantibodies. Frequent genetic mutations and progression to other immune dysregulation entities have been reported in a group of children with immune cytopenias. This might provide new insights focusing on the potential underlying genetic and epigenetic mechanisms leading to generation and maintenance of LLPCs in autoimmune disorders. We provide a brief review of LLPC biology and evidence for their role in immune cytopenias with potential future implications in this article.
免疫性血细胞减少症，如自身免疫性溶血性贫血、免疫性血小板减少症及Evans综合征，其特征为针对不同血细胞的自身抗体引发细胞破坏。T细胞、B细胞及其终末分化的浆细胞后代、树突状细胞与巨噬细胞间的相互作用导致抗体（包括自身反应性抗体）的产生。自身免疫现象可为特发性，亦可与多种免疫失调性疾病或恶性肿瘤相关。通过在不同层面干预这一复杂网络的疗法已被用于治疗免疫性血细胞减少症，并取得一定成效。部分病例对包括清除B细胞在内的多种治疗手段均表现难治性，而针对浆细胞的干预在此类病例中实现了疾病控制。在浆细胞群体中，主要定位于骨髓的长寿命浆细胞是一类具有延长存活期的特化抗体生成细胞，能够持续分泌抗体。这类细胞可规避针对增殖细胞的常规治疗策略。聚焦长寿命浆细胞在免疫性血细胞减少症等自身免疫现象中作用的研究，已证实其通过持续产生自身抗体参与疾病进程。有研究报道，部分免疫性血细胞减少症患儿存在高频基因突变，并可进展为其他免疫失调性疾病。这为探索自身免疫性疾病中长寿命浆细胞生成与维持的潜在遗传及表观遗传机制提供了新视角。本文简要综述长寿命浆细胞的生物学特性及其在免疫性血细胞减少症中的作用证据，并探讨其未来潜在临床意义。
A Room for Long-Lived Plasma Cell Contribution in Immune Cytopenias?
肿瘤(癌症)患者之家