■在过去的几十年里,冷凝集素病(CAD)的发病机制已得到很好的阐明,并被证明是复杂的。已经提供了几种记录在案的或研究性的疗法。这一发展导致了重大的治疗进展,但在选择治疗方面也面临挑战。
■在这篇评论中,我们解决了发病机制中的每个步骤:骨髓克隆性淋巴增生,单克隆冷凝集素的组成和作用,非补体介导的红细胞凝集,补体依赖性溶血,和补体激活的其他影响。我们还讨论了异质性的临床特征及其与发病机理中特定步骤的关系,特别是关于补充参与的影响。CAD可以分为三种临床表型,对已建立的治疗方法以及新疗法的开发具有影响。综述了一些有前途的未来治疗方法-化学免疫疗法和补体抑制。
■患者的补体受累和溶血性与非溶血性特征的个体临床特征对于治疗的选择很重要。鼓励进一步发展治疗方法,和一些候选药物是有前途的,无论临床表型。需要治疗的CAD患者应考虑纳入临床试验。
UNASSIGNED: During the last decades, the pathogenesis of cold agglutinin disease (CAD) has been well elucidated and shown to be complex. Several documented or investigational therapies have been made available. This development has resulted in major therapeutic advances, but also in challenges in choice of therapy.
UNASSIGNED: In this review, we address each step in pathogenesis: bone marrow clonal lymphoproliferation, composition and effects of monoclonal cold agglutinin, non-complement mediated erythrocyte agglutination, complement-dependent hemolysis, and other effects of complement activation. We also discuss the heterogeneous clinical features and their relation to specific steps in pathogenesis, in particular with respect to the impact of complement involvement. CAD can be classified into three clinical phenotypes with consequences for established treatments as well as development of new therapies. Some promising future treatment approaches - beyond chemoimmunotherapy and complement inhibition - are reviewed.
UNASSIGNED: The patient\'s individual clinical profile regarding complement involvement and hemolytic versus non-hemolytic features is important for the choice of treatment. Further development of treatment approaches is encouraged, and some candidate drugs are promising irrespective of clinical phenotype. Patients with CAD requiring therapy should be considered for inclusion in clinical trials.