Dijstelbloem H M, Bijl M, Fijnheer R, Scheepers R H, Oost W W, Jansen M D, Sluiter W J, Limburg P C, Derksen R H, van de Winkel J G, Kallenberg C G
University Hospital Groningen, The Netherlands.
Arthritis Rheum. 2000 Dec;43(12):2793-800. doi: 10.1002/1529-0131(200012)43:12<2793::AID-ANR20>3.0.CO;2-6.
Fc receptors for IgG (FcgammaR) play a prominent role in the clearance of immune complexes in systemic lupus erythematosus (SLE). Polymorphisms of FcgammaR have been proposed as genetic factors that influence susceptibility to SLE. We analyzed 3 functional FcgammaR polymorphisms in a strictly Caucasian population of SLE patients, and determined the influence of these polymorphisms on the clearance of immune complexes in vivo.
Genomic DNA was isolated from 230 Caucasian patients with SLE and 154 controls. Amplification of FcgammaR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. In addition, we analyzed the FcgammaR genotypes of 13 patients with SLE who participated in a study determining the half-life of IgG-coated erythrocytes in the blood.
We found a strong trend toward skewing of FcgammaRIIa, with an enrichment of the homozygous FcgammaRIIa-R/R131 genotype in patients compared with controls. We did not find a correlation between this genotype and the development of lupus nephritis. However, we established that the half-life of IgG-coated erythrocytes in the blood was prolonged in patients expressing the FcgammaRIIa-R/R131 genotype. The homozygous FcgammaRIIIa-F/F158 genotype was found more frequently in patients with arthritis and/or serositis.
In Caucasian populations, the R/H polymorphism of FcgammaRIIa is a minor determinant in susceptibility to SLE, whereas the V/F polymorphism of FcgammaRIIIa is associated with a set of disease manifestations. Notably, the R/H polymorphism of FcgammaRIIa affects the clearance of immune complexes in vivo, which may influence the course of a disease such as SLE.
免疫球蛋白G的Fc受体（FcγR）在系统性红斑狼疮（SLE）免疫复合物清除过程中发挥重要作用。FcγR基因多态性被认为是影响SLE易感性的遗传因素。我们在一个严格意义上的白种人SLE患者群体中分析了3种功能性FcγR基因多态性，并确定了这些多态性对体内免疫复合物清除的影响。
从230例白种人SLE患者和154例对照中分离基因组DNA。采用同种异型特异性聚合酶链反应扩增FcγR基因组区域以区分基因型。此外，我们分析了13例参与一项测定血液中IgG包被红细胞半衰期研究的SLE患者的FcγR基因型。
我们发现FcγRIIa有明显的偏态趋势，与对照组相比，患者中纯合FcγRIIa-R/R131基因型富集。我们未发现该基因型与狼疮性肾炎的发生之间存在相关性。然而，我们确定表达FcγRIIa-R/R131基因型的患者血液中IgG包被红细胞的半衰期延长。纯合FcγRIIIa-F/F158基因型在患有关节炎和/或浆膜炎的患者中更常见。
在白种人群体中，FcγRIIa的R/H多态性是SLE易感性的一个次要决定因素，而FcγRIIIa的V/F多态性与一组疾病表现相关。值得注意的是，FcγRIIa的R/H多态性影响体内免疫复合物的清除，这可能会影响诸如SLE等疾病的病程。
