Reviron D, Perdriger A, Toussirot E, Wendling D, Balandraud N, Guis S, Semana G, Tiberghien P, Mercier P, Roudier J
EFS Alpes Méditerranée, Marseilles, France.
Arthritis Rheum. 2001 Mar;44(3):535-40. doi: 10.1002/1529-0131(200103)44:3<535::AID-ANR101>3.0.CO;2-Z.
Most patients with rheumatoid arthritis (RA) express the shared epitope (SE). It is not known whether SE-negative HLA-DRB1 alleles influence the development of RA. This study examined the influence of SE-negative HLA-DR alleles (DRB1*X) on the development of RA in 3 different French populations.
HLA-DRB1 alleles were defined by polymerase chain reaction with sequence-specific oligonucleotide hybridization or sequence-specific primers. SE-negative alleles were classified according to the electric charge of their P4 pocket. HLA-DRB1 alleles *0103, *0402, *07, *08, *11 (except *1107), 12, and 13 have a neutral or negative P4 charge and are called DRB1XP4n. HLA-DRB103, *0403, *0406, *0407, *0901, *1107, *14, *15, and 16 have a positive P4 charge and are called DRB1XP4p.
Among the SE-negative subjects, DRB1 genotypes with 1 or 2 DRB1XP4n alleles were significantly overrepresented in the control subjects compared with the RA patients, whereas DRB1XP4p/XP4p genotypes were equally represented in the patients and controls. In single-dose SE-positive subjects, SE/XP4n genotypes were equally represented in the patients and controls. However, SE/XP4p genotypes were significantly overrepresented in the RA patients.
The DRB1X allele polymorphism influences susceptibility to RA. Alleles that have a neutral or negative electric charge in their P4 pocket (DRB1XP4n), such as DRB1*0103, *0402, *07, *08, *11 (except *1107), 12, and 13, protect against RA. Alleles that have a positive electric charge in their P4 pocket (DRB1XP4p), such as DRB103, *0403, *0406, *0407, *0901, *1107, *14, *15, and *16, have no influence on the predisposition to RA.
大多数类风湿关节炎（RA）患者表达共同表位（SE）。尚不清楚SE阴性的HLA - DRB1等位基因是否会影响RA的发病。本研究检测了SE阴性的HLA - DR等位基因（DRB1*X）对3个不同法国人群中RA发病的影响。
通过聚合酶链反应与序列特异性寡核苷酸杂交或序列特异性引物来确定HLA - DRB1等位基因。SE阴性等位基因根据其P4口袋的电荷进行分类。HLA - DRB1等位基因*0103、*0402、*07、*08、11（1107除外）、12和13具有中性或负性P4电荷，被称为DRB1XP4n。HLA - DRB103、*0403、*0406、*0407、*0901、*1107、14、15和16具有正性P4电荷，被称为DRB1XP4p。
在SE阴性受试者中，与RA患者相比，携带1个或2个DRB1XP4n等位基因的DRB1基因型在对照受试者中显著过量表达，而DRB1XP4p/XP4p基因型在患者和对照中表达相当。在单剂量SE阳性受试者中，SE/XP4n基因型在患者和对照中表达相当。然而，SE/XP4p基因型在RA患者中显著过量表达。
DRB1X等位基因多态性影响对RA的易感性。在其P4口袋中具有中性或负性电荷的等位基因（DRB1XP4n），如DRB1*0103、*0402、*07、*08、11（1107除外）、12和13，可预防RA。在其P4口袋中具有正性电荷的等位基因（DRB1XP4p），如DRB103、*0403、*0406、*0407、*0901、*1107、*14、15和16，对RA的易感性没有影响。
