Guerne P A, Salvi M, Seitz M, Bruhlmann P, Rivier G, Frey D, Mermillod B, Vischer T L, Tiercy J M
Division of Rheumatology, University Hospital, Geneva, Switzerland.
J Rheumatol. 1997 Apr;24(4):671-6.
To analyze by molecular typing possible associations of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) compared to controls and patients with rheumatoid arthritis (RA) in Switzerland.
In a multicenter survey, we recruited 100 patients with PMR with and without signs of giant cell arteritis (GCA), 198 with RA, and 200 controls (volunteer bone marrow donors). HLA-DR generic typing was performed by microtiter plate oligotyping and DR4 subtypes analyzed by dot blot hybridization with sequence specific oligonucleotides or by polymerase chain reaction sequence specific primers.
DR4 and DR1 tended to be increased in PMR, compared to controls (36 vs 30%, p = 0.30; and 19 vs 12%, p = 0.16, respectively). Frequencies of all RA associated DR4 and DR1 subtypes tended to be increased in PMR as well. Frequency of the HLA-DR beta 1 70-74 shared motif (QK/RRAA) was significantly higher in PMR than in controls [50 vs 36%, odds ratio (OR) = 1.8, p = 0.018], although lower than in RA (77 vs 36%, OR = 6.0, p < 0.0001), and slightly out of the range of significance if a Bonferroni correction was applied (p = 0.1). At double dose, this epitope was also increased in PMR, but not significantly (5 vs 2%, OR = 2.6, p = 0.17), while it was markedly augmented in RA (22 vs 2%, OR = 14, p = < 0.0001). In patients with the shared epitope, the frequency of clinical signs of GCA tended to be increased (19 vs 10%, p = 0.25). Frequency of the HLA-DR beta 1 DRYF 28-31 motif was identical in PMR (95%) and controls (93%).
PMR may be associated with the HLA-DR beta 1 70-74 shared epitope. This association, however, would be much weaker for PMR than for RA, particularly with the shared epitope at double dose. PMR is clearly not associated with the HLA-DR beta 1 DRYF 28-31 motif.
通过分子分型分析瑞士风湿性多肌痛（PMR）患者与对照组及类风湿关节炎（RA）患者相比，HLA - DRB1等位基因可能存在的关联。
在一项多中心调查中，我们招募了100例有或无巨细胞动脉炎（GCA）体征的PMR患者、198例RA患者以及200名对照者（志愿骨髓捐献者）。通过微量滴定板寡核苷酸分型法进行HLA - DR通用分型，并通过与序列特异性寡核苷酸的斑点杂交或聚合酶链反应序列特异性引物分析DR4亚型。
与对照组相比，PMR患者中DR4和DR1的比例有升高趋势（分别为36%对30%，p = 0.30；19%对12%，p = 0.16）。所有与RA相关的DR4和DR1亚型在PMR患者中的频率也有升高趋势。PMR患者中HLA - DRβ1 70 - 74共有基序（QK/RRAA）的频率显著高于对照组[50%对36%，优势比（OR）= 1.8，p = 0.018]，尽管低于RA患者（77%对36%，OR = 6.0，p < 0.0001），若应用Bonferroni校正则略超出显著范围（p = 0.1）。在双倍剂量时，该表位在PMR患者中也有所升高，但不显著（5%对2%，OR = 2.6，p = 0.17），而在RA患者中显著升高（22%对2%，OR = 14，p = < 0.0001）。在有共有表位的患者中，GCA临床体征的频率有升高趋势（19%对10%，p = 0.25）。PMR患者和对照组中HLA - DRβ1 DRYF 28 - 31基序的频率相同（均为95%和93%）。
PMR可能与HLA - DRβ1 70 - 74共有表位相关。然而，这种关联在PMR中比在RA中要弱得多，尤其是双倍剂量的共有表位。PMR显然与HLA - DRβ1 DRYF 28 - 31基序无关。
