Low expression levels of soluble CD1d gene in patients with rheumatoid arthritis.
Low expression levels of soluble CD1d gene in patients with rheumatoid arthritis.
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发表时间：
2003-12
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通讯作者：
S. Kojo;A. Tsutsumi;D. Goto;T. Sumida
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作者：
S. Kojo;A. Tsutsumi;D. Goto;T. Sumida
目的研究类风湿关节炎（RA）等自身免疫性疾病患者和健康人的完整CD 1d及其变体的表达是否存在差异。最近，我们确定了8种不同的CD 1d变体，由选择性剪接产生。缺乏外显子4的V1（CD 1d无β 2微球蛋白，β 2 m）和缺乏外显子4和5的V2（可溶性CD 1d）可能是功能分子，因为抗原结合位点（外显子2和3）是完整的。方法分离44例自身免疫性疾病患者（RA 19例，SLE 10例，Sjögren综合征15例，系统性红斑狼疮15例）和15例健康对照者的外周血单个核细胞（PBMC），制备互补（c）DNA。流式细胞术检测PBMC上完整CD 1d的表达。选择性剪接的CD 1d变体通过TaqMan PCR使用聚合酶链反应和基于对向2对引物（PCR-CTPP）的扩增进行定量。结果19例RA患者CD 1d跨膜和β 2 m结合位点缺失的mRNA水平（2.0 ± 0.33）显著低于15例对照组（6.9 ± 2.08; p < 0.05），而β 2 m缺失变异体和完整CD 1d mRNA水平无差异。结论可溶性CD 1d变异体的低表达可能参与了RA的发病过程。
OBJECTIVE To examine whether the expression of intact CD1d, a critical molecule for the presentation of glycolipid antigens to natural killer T (NKT) cells, and its variants differs between patients with autoimmune diseases including rheumatoid arthritis (RA) and healthy subjects. Recently, we identified 8 different CD1d variants, generated by alternative splicing. V1 lacking exon 4 (CD1d without beta2 microglobulin, beta2m) and V2 lacking exons 4 and 5 (soluble CD1d) may be functional molecules, because the antigen binding sites (exons 2 and 3) are intact. METHODS Peripheral blood mononuclear cells (PBMC) from 44 patients with autoimmune disease (RA 19, systemic lupus erythematosus, SLE 10, Sjögren's syndrome, SS 15) and 15 healthy controls were separated and complementary (c)DNA was prepared. The expression of intact CD1d on PBMC was detected by flow cytometry. Alternatively spliced CD1d variants were quantified by TaqMan PCR using polymerase chain reaction with confronting 2-pair primers (PCR-CTPP) based amplification. RESULTS The mean (+/- SEM) transmembrane and beta2m binding site deleted CD1d mRNA level in 19 patients with RA (2.0 +/- 0.33) was significantly lower than in 15 controls (6.9 +/- 2.08; p < 0.05), whereas there were no differences in beta2m deleted variants and intact CD1d mRNA. CONCLUSION Our findings suggest that low expression of soluble CD1d variants might play a role in the formation of symptoms or pathogenesis of RA.