Laivoranta-Nyman S, Möttönen T, Luukkainen R, Hakala M, Yli-Kerttula U, Hannonen P, Tuokko J, Toivanen A, Ilonen J
Turku Immunology Centre and Departments of Virology, Medical Microbiology and Medicine, University of Turku and Turku University Central Hospital, Turku, Finland.
Ann Rheum Dis. 2000 Mar;59(3):173-7. doi: 10.1136/ard.59.3.173.
To search for possible immunogenetic differencies between the patients with familial and non-familial rheumatoid arthritis (RA).
The study compared 129 familial RA patients with 217 non-familial patients for the frequencies of HLA-DR antigens including DR4 subtypes, DR4-DQB10301 and DR4-DQB10302 haplotypes and HLA-B27 antigen as well as the age of disease onset and existence of rheumatoid factor or joint erosions.
Two major differences between familial and non-familial groups were found: firstly, familial RA patients had increased frequency of HLA-DR4 as compared with the non-familial RA group (68.2 v. 54.8%; p = 0.019). Secondly, the mean age at onset of RA was significantly lower in the familial than in the sporadic RA patients (42.0 v. 46.5 years; p = 0.0020) and the difference still remained when the DR4 positive and negative subgroups were compared separately.
These results confirm the more prominent association with HLA-DR4 in familial than in the non-familial cases and suggest that accumulation of HLA risk genes may, at least partly, explain the familial occurrence of the disease. Other susceptibility genes may also be concentrated in multiplex case families as suggested by an earlier age at the onset of RA in both HLA-DR4 positive and negative familial patients.
探寻家族性和非家族性类风湿关节炎(RA)患者之间可能存在的免疫遗传学差异。
本研究比较了129例家族性RA患者和217例非家族性患者的HLA - DR抗原频率,包括DR4亚型、DR4 - DQB10301和DR4 - DQB10302单倍型以及HLA - B27抗原,同时比较了发病年龄、类风湿因子的存在情况或关节侵蚀情况。
在家族性和非家族性组之间发现了两个主要差异:其一,与非家族性RA组相比,家族性RA患者的HLA - DR4频率增加(68.2%对54.8%;p = 0.019)。其二,家族性RA患者的平均发病年龄显著低于散发性RA患者(42.0岁对46.5岁;p = 0.0020),并且在分别比较DR4阳性和阴性亚组时,这种差异仍然存在。
这些结果证实,与非家族性病例相比,家族性病例中与HLA - DR4的关联更为突出,提示HLA风险基因的积累可能至少部分解释了该疾病的家族性发病情况。正如HLA - DR4阳性和阴性家族性患者中RA发病年龄较早所表明的那样,其他易感基因也可能集中在多病例家庭中。