Department of Oncology, Scientific Institute San Raffaele, Milan, Italy.
Curr Opin Oncol. 2011 Sep;23(5):455-60. doi: 10.1097/CCO.0b013e328348c683.
Autoimmune cytopenia is a noninfrequent complication of chronic lymphocytic leukemia (CLL) classified into simple and complex autoimmunity, on the basis of the absence or the concomitance of disease progression. Simple-refractory and complex autoimmunity indicate the need of treatment. Here, we review the epidemiology and the biological mechanisms that account for CLL-associated autoimmune disorders and discuss their prognostic relevance and the indication of treatment.
Autoimmune disorders can complicate CLL at any stage and even occur in the preleukemic monoclonal B lymphocytosis. CLL cells can act as antigen-presenting cells, possibly inducing the formation of autoreactive T helper cells (through the production of B-cell activator factor and a proliferation-inducing ligand) and nonfunctional T regulatory cells (via CD27-CD70 interaction). Further, nonmalignant lymphocytes may stimulate via CD154-mediated mechanism both tumor growth and the development of autoimmunity, especially after fludarabine-based regimens of therapy. CLL cells tend to produce monoclonal polyreactive autoantibodies suggesting that autoantigen stimulation via B-cell receptor signaling may affect the natural history of CLL. Though the results of multivariate analysis do not allow to separate autoimmune disorders developing in CLL from conventional prognostic factors, the pathogenetic intertwining between autoimmunity and malignant transformation indicates the importance of defining whether the occurrence of autoimmunity in CLL might be considered an autonomous prognostic indicator that influences treatment decisions.
Simple-refractory and complex autoimmunity are independent indicators of therapy for CLL. Further, epidemiological and biological studies will help clarifying the prognostic and possibly also the pathogenetic significance of simple autoimmunity.
自身免疫性血细胞减少症是慢性淋巴细胞白血病（CLL）的一种非频繁并发症，根据疾病进展的有无或并存，可分为单纯和复杂自身免疫。单纯难治性和复杂自身免疫表明需要治疗。在此，我们回顾了导致 CLL 相关自身免疫紊乱的流行病学和生物学机制，并讨论了它们的预后意义和治疗指征。
自身免疫性疾病可在 CLL 的任何阶段并发，甚至在白血病前期的单克隆 B 淋巴细胞增多症中就可出现。CLL 细胞可作为抗原呈递细胞，可能通过产生 B 细胞激活因子和增殖诱导配体诱导自身反应性 T 辅助细胞的形成，并通过 CD27-CD70 相互作用产生无功能的 T 调节细胞。此外，非恶性淋巴细胞可能通过 CD154 介导的机制刺激肿瘤生长和自身免疫的发展，尤其是在基于氟达拉滨的治疗方案后。CLL 细胞往往产生单克隆多反应性自身抗体，这表明 B 细胞受体信号转导的自身抗原刺激可能影响 CLL 的自然病程。尽管多变量分析的结果不能将 CLL 中发生的自身免疫紊乱与常规预后因素分开，但自身免疫和恶性转化之间的病理交织表明，确定 CLL 中自身免疫的发生是否可以被认为是影响治疗决策的独立预后指标的重要性。
单纯难治性和复杂自身免疫是 CLL 治疗的独立指征。此外，流行病学和生物学研究将有助于阐明单纯自身免疫的预后意义，可能还有发病意义。
