University of California, San Francisco, Department of Pediatrics, Division of Pediatric Rheumatology, San Francisco, California, USA.
Curr Opin Rheumatol. 2018 Sep;30(5):498-505. doi: 10.1097/BOR.0000000000000523.
Autoimmune haemolytic anaemia (AIHA) and autoimmune thrombocytopenia are common complications of childhood-onset lupus, which may be life-threatening. A greater understanding of the pathogenesis of these haematologic manifestations will enhance our understanding of the biology of systemic lupus erythematosus (SLE) and inform the identification of novel treatments.
The mechanisms underlying AIHA and autoimmune thrombocytopenia are incompletely understood and likely multifactorial. Although the development of auto-antibodies is central to the disease process, recent studies have demonstrated the importance of cytokines in the underlying pathologic process. In-vitro and in-vivo evidence points to a role for IL17 in the pathogenesis of AIHA, which involves loss of tolerance to red cell auto-antigens and the development of autoantibodies. Sirolimus, an mTor inhibitor, has benefited patients with primary autoimmune cytopenias, possibly by stimulating T regulatory cells, and may also have efficacy for SLE-associated cytopenias. Similarly, low-dose recombinant human IL-2 therapy has shown promising results for improving platelet counts in patients with autoimmune thrombocytopenia, possibly by restoring the balance between T regulatory, T helper and Th17 cells.
The emergence of new agents directed at restoring immune dysregulation hold promise for the treatment of AIHA and autoimmune thrombocytopenia and should provide better tolerated alternatives to high-dose corticosteroids.
自身免疫性溶血性贫血（AIHA）和自身免疫性血小板减少症是儿童发病狼疮的常见并发症，可能危及生命。更深入地了解这些血液学表现的发病机制将有助于我们了解系统性红斑狼疮（SLE）的生物学，并为寻找新的治疗方法提供信息。
AIHA 和自身免疫性血小板减少症的发病机制尚不完全清楚，可能是多因素的。尽管自身抗体的产生是疾病过程的核心，但最近的研究表明细胞因子在潜在的病理过程中很重要。体外和体内证据表明白细胞介素 17（IL17）在 AIHA 的发病机制中起作用，涉及对红细胞自身抗原的耐受性丧失和自身抗体的产生。雷帕霉素（mTOR 抑制剂）已使原发性自身免疫性血细胞减少症患者受益，可能通过刺激 T 调节细胞，并且可能对 SLE 相关血细胞减少症也有效。同样，低剂量重组人白细胞介素 2 治疗对改善自身免疫性血小板减少症患者的血小板计数显示出良好的效果，可能通过恢复 T 调节细胞、辅助性 T 细胞和 Th17 细胞之间的平衡来实现。
针对恢复免疫失调的新药物的出现为治疗 AIHA 和自身免疫性血小板减少症带来了希望，并应为使用大剂量皮质类固醇激素提供更好的耐受性替代方案。
