Typiak M, Rębała K, Dudziak M, Słomiński J M, Dubaniewicz A
Department of Pulmonology, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
Department of Forensic Medicine, Medical University of Gdansk, 23 Debowa St, 80-204, Gdansk, Poland.
Adv Exp Med Biol. 2016;905:57-68. doi: 10.1007/5584_2015_193.
We have previously presented evidence that the polymorphism of the FCGR3A gene, encoding the receptor for Fc fragment of immunoglobulin G IIIa (FcγRIIIa) plays a role in the enhancement of circulating immune complexes (CIs) with the occurrence of Mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis (SA). The immunocomplexemia might be caused by decreased affinity of CIs to Fcγ receptors, with the subsequently decreased receptor clearance by immune cells. In the present study we examined whether the polymorphisms of other related genes (FCGR2A, FCGR2C, FCGR3B) encoding other activatory Fcγ receptors, could have a similar effect. To this end, we genotyped 124 patients with sarcoidosis and 148 healthy volunteers using polymerase chain reaction with sequence-specific primers. We revealed a significant decrease in the percentage of the FCGR2A and FCGR2C variants that ensure effective CIs clearance, with a concomitant increase of less functional variants of these genes in Stages I/II, compared with Stages III/IV of SA. There was no aberration in FCGR3B allele/genotype frequencies. We conclude that the FCGR2A and FCGR2C polymorphisms may also contribute to immunocomplexemia present in SA. The assessment of FCGR genes could become a tool in presaging a clinical course of sarcoidosis and in its personalized therapy.
我们之前已经提出证据表明，编码免疫球蛋白G IIIa（FcγRIIIa）Fc片段受体的FCGR3A基因多态性，在结节病（SA）患者中，随着结核分枝杆菌热休克蛋白的出现，在循环免疫复合物（CIs）增强中发挥作用。免疫复合物血症可能是由于CIs与Fcγ受体的亲和力降低，随后免疫细胞对受体的清除减少所致。在本研究中，我们检测了编码其他激活型Fcγ受体的其他相关基因（FCGR2A、FCGR2C、FCGR3B）的多态性是否会有类似作用。为此，我们使用序列特异性引物的聚合酶链反应对124例结节病患者和148名健康志愿者进行基因分型。我们发现，与SA的III/IV期相比，在I/II期，确保有效清除CIs的FCGR2A和FCGR2C变体百分比显著降低，同时这些基因功能较差的变体增加。FCGR3B等位基因/基因型频率没有异常。我们得出结论，FCGR2A和FCGR2C多态性也可能导致SA中存在的免疫复合物血症。FCGR基因的评估可能成为预测结节病临床病程及其个性化治疗的一种工具。
