Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders
Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders
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DOI：
10.1002/art.10898
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发表时间：
2003-04-01
影响因子：
--
通讯作者：
Benoist, C
中科院分区：
文献类型：
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作者：
Matsumoto, I;Lee, DM;Benoist, C
客观的。 K/BxN 小鼠模型中的关节炎是由识别葡萄糖-6-磷酸异构酶 (GPI) 的致病性免疫球蛋白引起的，GPI 是一种存在于所有细胞细胞质中的糖酵解酶。仅针对 GPI 的抗体就可以将关节炎转移给健康的接受者。先前的实验表明，许多类风湿性关节炎 (RA) 患者的血清中存在显着滴度的抗 GPI 抗体。我们在患有 12 种不同关节炎和慢性自身免疫性疾病的患者队列以及人群匹配的健康对照受试者中评估了这些观察结果的普遍性。方法。通过酶联免疫吸附测定法，使用 2 种形式的 GPI（重组型和天然型）对 811 份个体血清样本中的抗 GPI 抗体进行了测定。结果通过免疫印迹证实。结果。一些患者的抗 GPI 抗体滴度显着升高，但没有以前报道的普遍性或特异性。只有 15% 的 RA 患者具有抗 GPI 抗体（不同队列中的范围为 12-29%），在活动性疾病患者中患病率更高。银屑病关节炎、未分化关节炎和脊柱关节病患者也以相似的频率（12-25%）表现出抗 GPI 抗体。在一定比例（5-10%）的对照受试者或患有克罗恩病或结节病的患者中检测到类似的滴度。在罕见的 RA 和系统性红斑狼疮病例中发现了非常高的滴度。结论。没有明显的疾病特异性 GPI 抗体阳性模式。虽然小鼠模型中抗体介导的机制可能体现了人类某些形式关节炎的一般机制，但 GPI 本身似乎并不是大多数 RA 患者共同的靶点。
Objective. Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti-GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population-matched healthy control subjects.Methods. Anti-GPI antibodies were assayed in 811 individual serum samples by enzyme-linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting.Results. Several patients had significantly elevated anti-GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti-GPI antibodies (range 12-29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti-GPI antibodies at similar frequencies (12-25%). Similar titers were detected in a proportion (5-10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus.Conclusion. No disease-specific pattern of antibody positivity to GPI was apparent. While the antibody-mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients.