Manger K, Repp R, Jansen M, Geisselbrecht M, Wassmuth R, Westerdaal N A C, Pfahlberg A, Manger B, Kalden J R, van de Winkel J G J
Department of Internal Medicine III and Institute for Clinical Immunology, University Erlangen-Nuremberg, Germany.
Ann Rheum Dis. 2002 Sep;61(9):786-92. doi: 10.1136/ard.61.9.786.
Receptors for IgG play an important part in immune complex clearance. Several studies have identified polymorphisms of receptors for the Fc fragment of IgG (FcgammaR) as genetic factors influencing susceptibility to disease or disease course of systemic lupus erythematosus (SLE).
To examine these possibilities by evaluating a panel of clinical parameters in a cohort of 140 German patients with SLE for correlations with the FcgammaRIIa, IIIa, and IIIb polymorphisms in an explorative study.
140 German patients with SLE according to American College of Rheumatology (ACR) criteria and 187 German controls were genotyped for the FcgammaRIIa, IIIa, and IIIb polymorphisms. Associations between FcgammaR genotypes, combined genotypes and clinical as well as laboratory features were analysed.
No significant skewing of any of the three FcgammaR polymorphisms was seen in the German SLE cohort studied. Various clinical and serological parameters were found more frequently and at younger age in homozygous patients with the genotypes IIA-R/R131 or IIIA-F/F158 than in patients with IIA-H/H131 or IIIA-V/V158. These effects were even more pronounced in patients with the low binding combined phenotypes of the FcgammaRIIa, IIIa (double negative phenotypes) and FcgammaRIIa, IIIa, and IIIb (triple negative phenotypes). In patients with the double negative IIA and IIIA genotypes significantly higher frequencies of nephritis (63% v 33%) and proteinuria according to ACR criteria (58% v 11%), anaemia (84% v 55%), and anticardiolipin antibodies (63% v 22%) were found than in patients with the double positive genotypes. Patients with the IIA-R/R131 genotype and the double negative homozygous genotype had an earlier incidence of clinical symptoms, haematological and immunological abnormalities. Accordingly, SLE is diagnosed earlier in these patients, the difference reaching statistical significance only in the double negative v the double positive genotype (26.3 v 39.5 years) and the IIIA-F/F158 genotype v the rest (26.7 v 32.0 years). Most relevant is the fact that a higher median disease activity (ECLAM score) was demonstrated, both in the IIA-R/R131 homozygous (3.3 v 2.7) and the double negative (3.4 v 2.3) patients, reaching statistical significance in the first group.
The results of this explorative study support the view that the FcgammaRIIa/IIIa and IIIb polymorphisms constitute factors influencing clinical manifestations and the disease course of SLE but do not represent genetic risk factors for the occurrence of SLE. Higher frequencies of clinical symptoms, haematological and immunological abnormalities as well as an earlier onset of clinical symptoms, haematological and immunological markers of active disease were found in patients with the IIA-R/R131 genotype and the double negative and triple negative genotypes.
IgG受体在免疫复合物清除中起重要作用。多项研究已确定IgG Fc片段受体（FcγR）的多态性是影响系统性红斑狼疮（SLE）易感性或疾病进程的遗传因素。
在一项探索性研究中，通过评估140例德国SLE患者队列中的一组临床参数与FcγRIIa、IIIa和IIIb多态性的相关性，来检验这些可能性。
根据美国风湿病学会（ACR）标准，对140例德国SLE患者和187例德国对照进行FcγRIIa、IIIa和IIIb多态性基因分型。分析FcγR基因型、联合基因型与临床及实验室特征之间的关联。
在所研究的德国SLE队列中，未发现三种FcγR多态性中的任何一种有明显偏态。与IIA-H/H131或IIIA-V/V158基因型的患者相比，基因型为IIA-R/R131或IIIA-F/F158的纯合患者中，各种临床和血清学参数出现得更频繁且年龄更小。这些效应在具有FcγRIIa、IIIa低结合联合表型（双阴性表型）以及FcγRIIa、IIIa和IIIb（三阴性表型）的患者中更为明显。在双阴性IIA和IIIA基因型的患者中，根据ACR标准，肾炎（63%对33%）、蛋白尿（58%对11%）、贫血（84%对55%）和抗心磷脂抗体（63%对22%）的发生率显著高于双阳性基因型的患者。具有IIA-R/R131基因型和双阴性纯合基因型的患者临床症状、血液学和免疫学异常的发病时间更早。因此，这些患者的SLE诊断更早，仅在双阴性对双阳性基因型（26.3对39.5岁）以及IIIA-F/F158基因型对其他基因型（26.7对32.0岁）时差异具有统计学意义。最相关的是，IIA-R/R131纯合子（3.3对2.7）和双阴性（3.4对2.3）患者的疾病活动中位数（ECLAM评分）更高，在第一组中具有统计学意义。
这项探索性研究的结果支持以下观点，即FcγRIIa/IIIa和IIIb多态性是影响SLE临床表现和疾病进程的因素，但不是SLE发生的遗传危险因素。在具有IIA-R/R131基因型以及双阴性和三阴性基因型的患者中，临床症状、血液学和免疫学异常的发生率更高，且临床症状、活动性疾病的血液学和免疫学标志物的发病时间更早。
