Berentsen Sigbjørn
Department of Research and Innovation, Haugesund Hospital, Haugesund, Norway.
Front Immunol. 2020 Apr 7;11:590. doi: 10.3389/fimmu.2020.00590. eCollection 2020.
Autoimmune hemolytic anemias mediated by cold agglutinins can be divided into cold agglutinin disease (CAD), which is a well-defined clinicopathologic entity and a clonal lymphoproliferative disorder, and secondary cold agglutinin syndrome (CAS), in which a similar picture of cold-hemolytic anemia occurs secondary to another distinct clinical disease. Thus, the pathogenesis in CAD is quite different from that of polyclonal autoimmune diseases such as warm-antibody AIHA. In both CAD and CAS, hemolysis is mediated by the classical complement pathway and therefore can result in generation of anaphylotoxins, such as complement split product 3a (C3a) and, to some extent, C5a. On the other hand, infection and inflammation can act as triggers and drivers of hemolysis, exemplified by exacerbation of CAD in situations with acute phase reaction and the role of specific infections (particularly and Epstein-Barr virus) as causes of CAS. In this review, the putative mechanisms behind these phenomena will be explained along with other recent achievements in the understanding of pathogenesis in these disorders. Therapeutic approaches have been directed against the clonal lymphoproliferation in CAD or the underlying disease in CAS. Currently, novel targeted treatments, in particular complement-directed therapies, are also being rapidly developed and will be reviewed.
由冷凝集素介导的自身免疫性溶血性贫血可分为冷凝集素病（CAD）和继发性冷凝集素综合征（CAS），前者是一种明确的临床病理实体，属于克隆性淋巴细胞增殖性疾病，后者是继发于另一种不同临床疾病的类似冷凝集素性溶血性贫血表现。因此，CAD的发病机制与多克隆自身免疫性疾病如温抗体型自身免疫性溶血性贫血（AIHA）有很大不同。在CAD和CAS中，溶血均由经典补体途径介导，因此可导致过敏毒素的产生，如补体裂解产物3a（C3a）以及在一定程度上的C5a。另一方面，感染和炎症可作为溶血的触发因素和驱动因素，如在急性期反应情况下CAD病情加重以及特定感染（尤其是EB病毒）作为CAS病因所起的作用。在本综述中，将解释这些现象背后的潜在机制以及在这些疾病发病机制理解方面的其他最新成果。治疗方法针对CAD中的克隆性淋巴细胞增殖或CAS中的基础疾病。目前，新型靶向治疗，特别是补体导向治疗，也在迅速发展，并将进行综述。
