University of Brescia, Brescia, Italy.
University of Milan and IRCCS Istituto Auxologico Italiano, Milan, Italy.
Arthritis Rheumatol. 2015 May;67(8):2196-204. doi: 10.1002/art.39187.
It has been suggested that only antibodies against domain 1 (D1) of β2 -glycoprotein I (β2 GPI) are pathogenic and diagnostic. The role of antibodies against other β2 GPI domains is still debated. This study was undertaken to evaluate the clinical relevance of domain specificity profiling of anti-β2 GPI IgG antibodies in antiphospholipid syndrome (APS) patients and in control groups of patients with systemic autoimmune rheumatic diseases and in asymptomatic antiphospholipid antibody (aPL) carriers.
We evaluated 159 subjects with persistently positive, medium or high-titer anti-β2 GPI IgG, including 56 patients with thrombotic (obstetric or nonobstetric) primary APS, 31 women with obstetric primary APS, 42 aPL-positive patients with systemic autoimmune rheumatic diseases, and 30 asymptomatic aPL carriers. One hundred healthy donors were included. Anti-β2 GPI D1 and D4/5 IgG were tested on research enzyme-linked immunosorbent assays containing recombinant β2 GPI domains.
As compared to other groups, aPL carriers displayed higher frequency/titer of anti-D4/5 IgG. Unlike anti-D4/5, anti-D1 IgG antibodies were more frequent and at higher titer in triple than in single or double aPL-positive subjects. An anti-D1 to anti-D4/5 ratio of ≥1.5 was predictive of systemic autoimmunity (odds ratio 3.25 [95% confidence interval 1.45-7.49], P = 0.005). Neither anti-D1 nor anti-D4/5 antibodies were associated with APS clinical criteria.
Anti-D1 IgG is the preferential specificity not only in vascular and obstetric primary APS, but also in patients with systemic autoimmune rheumatic disease with no clinical features of APS. Conversely, aPL carriers do not have a polarized profile toward D1. Combined testing for anti-β2 GPI IgG with different domain specificity allows a more accurate aPL profiling, with polarization toward anti-D1 IgG as a possible fingerprint of systemic autoimmunity.
有人认为，只有针对β2-糖蛋白 I（β2 GPI）结构域 1（D1）的抗体才具有致病性和诊断性。针对其他β2 GPI 结构域的抗体的作用仍存在争议。本研究旨在评估抗β2 GPI IgG 抗体的结构域特异性谱分析在抗磷脂综合征（APS）患者、系统性自身免疫性风湿病患者及无症状抗磷脂抗体（aPL）携带者中的临床相关性。
我们评估了 159 例持续存在高、中或高滴度抗β2 GPI IgG 的患者，包括 56 例血栓形成（产科或非产科）原发性 APS 患者、31 例产科原发性 APS 患者、42 例 aPL 阳性的系统性自身免疫性风湿病患者和 30 例无症状 aPL 携带者。另外纳入 100 名健康供者。使用包含重组β2 GPI 结构域的研究性酶联免疫吸附试验检测抗β2 GPI D1 和 D4/5 IgG。
与其他组相比，aPL 携带者的抗 D4/5 IgG 频率/滴度更高。与抗 D4/5 不同，三重 aPL 阳性患者的抗 D1 IgG 抗体更频繁且滴度更高。抗 D1 与抗 D4/5 的比值≥1.5 可预测系统性自身免疫（比值比 3.25 [95%置信区间 1.45-7.49]，P = 0.005）。抗 D1 和抗 D4/5 抗体均与 APS 临床标准无关。
抗 D1 IgG 不仅是血管性和产科原发性 APS 的首选特异性抗体，也是无 APS 临床特征的系统性自身免疫性风湿病患者的首选特异性抗体。相反，aPL 携带者对 D1 没有偏极化的特征。针对不同结构域特异性的抗β2 GPI IgG 进行联合检测可更准确地进行抗磷脂抗体谱分析，抗 D1 IgG 极化可能是系统性自身免疫的特征。
