A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis
A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis
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DOI：
10.1186/ar2131
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发表时间：
2007-01-01
影响因子：
4.9
通讯作者：
Constantin, Arnaud
中科院分区：
文献类型：
--
作者：
Gourraud, Pierre-Antoine;Dieude, Philippe;Constantin, Arnaud
HLA-DRB 1基因与类风湿关节炎（RA）患者抗瓜氨酸蛋白/肽自身抗体（ACPA）的产生有关。HLA-DRB 1等位基因的新分类，重塑共享表位（SE）假说，我们研究了HLA-DRB 1 SE（+）等位基因的这种新分类与类风湿因子（RF）的相关性，我们研究了160名早期RA患者，这些患者被纳入一个前瞻性的法国白人患者纵向队列，最近才发作的关节炎在入选时对所有患者的RF、抗环瓜氨酸肽2（抗CCP 2）和抗脱亚氨基人纤维蛋白原自身抗体（AhFibA）进行了评估。应用序列特异性寡核苷酸探针（PCR-SSOP）对HLA-DRB 1基因进行分型，根据新的分类法将SE（+）等位基因分为S1、S2、S3 P、S3 D四组，区分了RF、抗CCP 2和AhFibA的易感和保护等位基因。S2或S3 P等位基因的存在与RF、抗CCP 2或AhFibA阳性相关，而S3 D或S1等位基因的存在似乎对RF、抗CCP 2或AhFibA阳性具有保护作用。通过区分RF或ACPA产生的易感和保护等位基因，HLA-DRB 1 SE（+）等位基因的新分类与早期RA患者自身抗体产生相关。
The HLA-DRB1 gene was reported to be associated with anticitrullinated protein/peptide autoantibody (ACPA) production in rheumatoid arthritis (RA) patients. A new classification of HLA-DRB1 alleles, reshaping the shared epitope (SE) hypothesis, was recently found relevant in terms of RA susceptibility and structural severity.We investigated the relevance of this new classification of HLA-DRB1 SE(+) alleles in terms of rheumatoid factor (RF) and ACPA production in a sample of French RA patients.We studied 160 early RA patients included in a prospective longitudinal cohort of French Caucasian patients with recent-onset arthritis. RF, anticyclic citrullinated peptide 2 (anti-CCP2) and antideiminated human fibrinogen autoantibodies (AhFibA) were assessed in all patients at inclusion. The HLA-DRB1 gene was typed by PCR-sequence specific oligonucleotides probes (PCR-SSOP), and SE(+) alleles were classified into four groups (S1, S2, S3P, S3D) according to the new classification.The new classification of HLA-DRB1 SE(+) alleles distinguishes predisposing and protective alleles for RF, anti-CCP2 or AhFibA production. The presence of S2 or S3P alleles is associated with both RF, anti-CCP2 or AhFibA positivity, whereas the presence of S3D or S1 alleles appears to be protective for RF, anti-CCP2 or AhFibA positivity.The new classification of HLA-DRB1 SE(+) alleles is relevant in terms of autoantibody production in early RA patients by differentiating predisposing and protective alleles for RF or ACPA production.