Blank M, Krause I, Magrini L, Spina G, Kalil J, Jacobsen S, Thiesen H J, Cunningham M W, Guilherme L, Shoenfeld Y
Research Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel.
Rheumatology (Oxford). 2006 Jul;45(7):833-41. doi: 10.1093/rheumatology/kel118. Epub 2006 May 16.
Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic molecules engaged in these autoimmune conditions.
Sera from the APS patients were affinity-purified on beta2GPI and beta2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The beta2GPI and M protein-related peptides were prepared by conventional solid-phase peptide synthesis. The enzyme-linked immunosorbent assay direct binding and inhibition studies were performed on the RF and APS sera for the presence, and cross-reactivity, of antibodies against beta2GPI, beta2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc.
Antibodies (Abs) to beta2GPI were found in 24.4% of 90 RF patients. Antibodies against various beta2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-beta2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-beta2GPI and anti-beta2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while beta2GPI and beta2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The beta2GPI also inhibited anti-GlcNAc activity from APS patients with chorea.
The results of our study, showing a considerable overlap of humoral immunity in RF and APS, support a hypothesis that common pathogenic mechanisms underlie the development of cardiac valve lesions and Central Nervous System abnormalities in both diseases.
风湿热（RF）和抗磷脂综合征（APS）是自身免疫性疾病，具有相似的心脏和神经病理学特征。我们评估了参与这些自身免疫性疾病的致病分子——M蛋白、N - 乙酰 - β - D - 氨基葡萄糖（GlcNAc）和β2糖蛋白 - I（β2GPI）之间共有表位的存在情况。
将APS患者的血清在β2GPI和β2GPI相关肽柱上进行亲和纯化。将RF患者的血清在蛋白G柱上进行亲和纯化。通过常规固相肽合成制备β2GPI和M蛋白相关肽。对RF和APS血清进行酶联免疫吸附测定直接结合和抑制研究，以检测抗β2GPI、β2GPI相关肽、链球菌M蛋白、M衍生肽和GlcNAc抗体的存在及交叉反应性。
在90例RF患者中，24.4%的患者检测到抗β2GPI抗体。1.1% - 36.7%的患者检测到针对各种β2GPI相关肽的抗体。RF患者的免疫球蛋白G血清具有显著的抗β2GPI活性，而APS患者的血清含有相当水平的抗链球菌M蛋白以及抗GlcNAc活性。此外，从APS患者中亲和纯化的抗β2GPI和抗β2GPI相关肽抗体与链球菌M蛋白和M5肽发生交叉反应，而β2GPI和β2GPI相关肽抑制RF患者的抗链球菌M蛋白活性。免疫印迹分析证实了结果。β2GPI还抑制了患有舞蹈病的APS患者的抗GlcNAc活性。
我们的研究结果显示RF和APS在体液免疫方面有相当程度的重叠，支持了一种假设，即这两种疾病中心脏瓣膜病变和中枢神经系统异常的发生存在共同的致病机制。
