MacGregor A J, Ollier W E, Venkovsky J, Mageed R A, Carthy D, Silman A J
ARC Epidemiology Research Unit, Manchester, UK.
J Rheumatol. 1995 Dec;22(12):2203-7.
To examine the influence of genetic factors in determining the occurrence of rheumatoid factor (RF) isotypes. We investigated the hypothesis that, in twin pairs discordant for rheumatoid arthritis (RA), a genetic influence would be indicated by a higher rate of occurrence of RF among the unaffected monozygotic (MZ) when compared with the unaffected dizygotic (DZ) co-twins of seropositive affected twins.
IgM, IgA, and IgG RF were measured by ELISA in 70 MZ and 84 DZ disease discordant pairs using a cutoff for seropositivity defined using a normal control population. The risk of seropositivity in the unaffected twins of MZ when compared with DZ seropositive index twins was examined using odds ratios (OR).
For all 3 RF isotypes, levels in the unaffected twins of seropositive index twins were higher than in the control population. MZ unaffected twins showed an increased risk for seropositivity for IgM and IgG RF when compared with DZ unaffected twins: IgM OR = 2.2 (95% CI 0.9-5.4), IgG OR = 2.4 (95% CI 0.9-6.6). The greatest excess risk for seropositivity occurred for IgM RF amongst the unaffected twin of an index twin with past or current documented evidence of RF seropositivity, OR = 3.4 (95% CI 1.4-8.5). For IgA RF, seropositivity risk in MZ unaffected twins was not increased, OR = 1.0 (0.3-3.1). The seropositivity risk for all 3 isotypes was independent of the age of the pair, the age of disease onset in the index twin, and the sex, HLA-DRB101 and DRB104 status of the unaffected twin.
Genetic factors are important in determining the level of IgM and IgG RF. A genetic contribution to RA seropositivity exists that is independent of HLA-DR.
研究遗传因素在决定类风湿因子（RF）亚型出现中的作用。我们调查了以下假设：在类风湿关节炎（RA）不一致的双胞胎对中，与血清阳性受累双胞胎的未受累异卵（DZ）双胞胎相比，未受累同卵（MZ）双胞胎中RF的发生率更高，这将表明存在遗传影响。
使用基于正常对照人群定义的血清阳性临界值，通过酶联免疫吸附测定（ELISA）法检测了70对MZ和84对疾病不一致的DZ双胞胎对中的IgM、IgA和IgG RF。使用优势比（OR）来检验与DZ血清阳性指数双胞胎相比，MZ未受累双胞胎血清阳性的风险。
对于所有3种RF亚型，血清阳性指数双胞胎的未受累双胞胎中的水平均高于对照人群。与DZ未受累双胞胎相比，MZ未受累双胞胎中IgM和IgG RF血清阳性的风险增加：IgM的OR = 2.2（95%可信区间0.9 - 5.4），IgG的OR = 2.4（95%可信区间0.9 - 6.6）。在有既往或当前记录的RF血清阳性证据的指数双胞胎的未受累双胞胎中，IgM RF血清阳性的额外风险最大，OR = 3.4（95%可信区间1.4 - 8.5）。对于IgA RF，MZ未受累双胞胎血清阳性的风险没有增加，OR = 1.0（0.3 - 3.1）。所有3种亚型的血清阳性风险均与双胞胎对的年龄、指数双胞胎的疾病发病年龄以及未受累双胞胎的性别、HLA - DRB101和DRB104状态无关。
遗传因素在决定IgM和IgG RF水平方面很重要。存在一种独立于HLA - DR的对RA血清阳性的遗传贡献。
