Harmer I J, Loizou S, Thompson K M, So A K, Walport M J, Mackworth-Young C
Royal Postgraduate Medical School, London, England.
Arthritis Rheum. 1995 Aug;38(8):1068-76. doi: 10.1002/art.1780380808.
To investigate the origins of antiphospholipid antibodies associated with thrombosis and other disorders that are found in patients with systemic lupus erythematosus and primary antiphospholipid syndrome (APS).
Characterization, idiotypic study, and nucleotide sequencing of a human monoclonal antiphospholipid antibody generated from a patient with primary APS. Identification of the germline genes from which the antibody is derived.
A human monoclonal antibody, BH1, was generated. This antibody has ligand-binding properties that closely resemble those of the serum antiphospholipid antibodies found in our patient and in other individuals with APS: it recognizes negatively charged phospholipids, and has lupus anticoagulant activity; it does not bind to neutral phospholipids, or to single-stranded or double-stranded DNA. The relevance of BH1 to the patient's serum antibodies is supported by our idiotypic studies. BH1 is encoded by a new germline VH gene, and by a lambda light chain gene that displays > 99% homology with the V lambda III.1 germline gene.
Serum antiphospholipid antibodies associated with thrombosis may be encoded by either germline or only slightly mutated variable-region genes.
研究系统性红斑狼疮和原发性抗磷脂综合征（APS）患者体内与血栓形成及其他病症相关的抗磷脂抗体的起源。
对一名原发性APS患者产生的人源单克隆抗磷脂抗体进行表征、独特型研究及核苷酸测序。鉴定该抗体所源自的种系基因。
产生了一种人源单克隆抗体BH1。该抗体具有与我们的患者及其他APS个体血清中抗磷脂抗体极为相似的配体结合特性：它识别带负电荷的磷脂，具有狼疮抗凝活性；不与中性磷脂、单链或双链DNA结合。独特型研究支持了BH1与患者血清抗体的相关性。BH1由一个新的种系VH基因及一个与VλIII.1种系基因显示出>99%同源性的λ轻链基因编码。
与血栓形成相关的血清抗磷脂抗体可能由种系基因或仅发生轻微突变的可变区基因编码。
