Rahman A, Menon S, Latchman D S, Isenberg D A
Bloomsbury Rheumatology Unit/Division of Rheumatology, Department of Medicine, University College, London.
Semin Arthritis Rheum. 1996 Oct;26(2):515-25. doi: 10.1016/s0049-0172(96)80040-0.
Antiphospholipid antibodies (aPL) are recognized increasingly as a probable cause of clinical features such as thrombosis and recurrent miscarriages, particularly in a subset of patients with systemic lupus erythematosus (SLE) and those with the antiphospholipid antibody syndrome (APS). A powerful method of studying the origin of these antibodies and delineating their binding sites is to sequence monoclonal aPL. The few reports of mouse aPL sequences suggest that gene families J558 and Vk23 may be used preferentially but without extensive mutation of complementarity determining regions (CDR). Polyreactive human aPL, which bind DNA as well as phospholipids, generally use germline genes with few mutations. Specific immunoglobulin (Ig) M aPL also tend to use relatively unmutated genes but often have high concentrations of positive residues in CDR, which may enhance binding to anionic phospholipids. IgG aPL show many more antigen-selected mutations, particularly in heavy chain CDR. This difference between isotypes is similar to that seen in anti-DNA antibodies, but the role of positively charged residues in aPL is less evident, and additional motifs are likely to be important in antigen binding.
抗磷脂抗体（aPL）越来越被认为是导致血栓形成和反复流产等临床症状的一个可能原因，尤其在系统性红斑狼疮（SLE）患者亚群以及抗磷脂抗体综合征（APS）患者中。研究这些抗体起源并确定其结合位点的一种有效方法是对单克隆aPL进行测序。关于小鼠aPL序列的少数报告表明，基因家族J558和Vk23可能被优先使用，但互补决定区（CDR）没有广泛突变。能结合DNA以及磷脂的多反应性人aPL通常使用突变较少的种系基因。特异性免疫球蛋白（Ig）M aPL也倾向于使用相对未突变的基因，但在CDR中往往有高浓度的带正电荷残基，这可能增强与阴离子磷脂的结合。IgG aPL显示出更多的抗原选择突变，尤其是在重链CDR中。不同同种型之间的这种差异与抗DNA抗体中的情况相似，但aPL中带正电荷残基的作用不太明显，并且其他基序在抗原结合中可能很重要。
