Gourraud Pierre-Antoine, Boyer Jean-Frédéric, Barnetche Thomas, Abbal Michel, Cambon-Thomsen Anne, Cantagrel Alain, Constantin Arnaud
INSERM U558, Toulouse, France.
Arthritis Rheum. 2006 Feb;54(2):593-9. doi: 10.1002/art.21630.
A new classification of HLA-DRB1 alleles supporting the shared epitope hypothesis of rheumatoid arthritis (RA) susceptibility was recently introduced. We investigated the relevance of this classification in terms of the structural severity of RA.
The study group comprised 144 patients who were included in a prospective longitudinal cohort of French Caucasoid patients with early RA. Progression of the total radiographic damage score (Sharp/van der Heijde method) was used to quantify the structural severity of RA after 4 years of followup. HLA-DRB1 typing and subtyping were performed by polymerase chain reaction, using a panel of sequence-specific oligonucleotide probes. HLA-DRB1 alleles were classified according to the above-mentioned new system. The association between the HLA-DRB1 allele groups (S1, S2, S3P, S3D, and X) and the structural severity of RA was analyzed with nonparametric statistical tests.
The presence of S2 alleles (HLA-DRB10401 and HLA-DRB11303) was associated with severe forms of RA (P = 0.004); a significant dose effect was observed (P = 0.01). The presence of S3D alleles (HLA-DRB111001, HLA-DRB11104, HLA-DRB112, and HLA-DRB116) was associated with benign forms of RA (P < 0.0001), and a significant dose effect was observed (P < 0.01).
The studied classification of HLA-DRB1 alleles is relevant in terms of RA outcomes. Compared with a previously described classification system, this system differentiates predisposing (S2) and protective (S3D) alleles for RA structural severity, which, respectively, correspond to KRRAA and DRRAA amino acid patterns at position 70-74 of the third hypervariable region of the HLA-DRbeta chain.
最近引入了一种支持类风湿关节炎（RA）易感性共享表位假说的HLA - DRB1等位基因新分类。我们从RA的结构严重程度方面研究了这种分类的相关性。
研究组包括144例患者，这些患者被纳入一个法国白种人早期RA患者的前瞻性纵向队列。采用总放射学损伤评分（Sharp/van der Heijde方法）的进展情况来量化随访4年后RA的结构严重程度。通过聚合酶链反应，使用一组序列特异性寡核苷酸探针进行HLA - DRB1分型和亚型分析。HLA - DRB1等位基因根据上述新系统进行分类。采用非参数统计检验分析HLA - DRB1等位基因组（S1、S2、S3P、S3D和X）与RA结构严重程度之间的关联。
S2等位基因（HLA - DRB10401和HLA - DRB11303）的存在与严重形式的RA相关（P = 0.004）；观察到显著的剂量效应（P = 0.01）。S3D等位基因（HLA - DRB111001、HLA - DRB11104、HLA - DRB112和HLA - DRB116）的存在与良性形式的RA相关（P < 0.0001），并且观察到显著的剂量效应（P < 0.01）。
所研究的HLA - DRB1等位基因分类在RA结局方面具有相关性。与先前描述的分类系统相比，该系统区分了RA结构严重程度的易感（S2）和保护（S3D）等位基因，它们分别对应于HLA - DRβ链第三个高变区70 - 74位的KRRAA和DRRAA氨基酸模式。
