免疫性血小板减少症患者FcγRⅡA、FcγRⅢA、FcγRⅡB基因多态性及其临床意义初探

Polymorphisms of FcγRⅡA,FcγRⅢA and FcγRⅡB in Patients with Immune Thrombocytopenia and their Clinical Significance

本研究旨在探讨FcγR基因多态性与免疫性血小板减少症(ITP)患者疾病易感性、严重程度及疗效之间的关系。通过PCR扩增和DNA测序检测44例ITP患者及97例健康对照者的FcγRⅡA、FcγRⅢA及FcγRⅡB多态性。结果发现:①FcγRⅢA-158V/F多态性分布在ITP组与对照组间有显著差异(P=0.015),158V/V基因型比例在ITP组明显增高(P=0.005),而FcγRⅡA-131H/R、FcγRⅡB-232T/I多态性分布在ITP组与对照组之间无显著差异;②患者发病时血小板计数及病程与FcγRⅡA、FcγRⅢA及FcγRⅡB各基因型分布均无明显相关性;③38例接受治疗的ITP患者中16例(42%)达完全缓解(CR),13例(34%)达部分缓解(PR),FcγRⅢA-158V/V基因型与158F/V基因型疗效存在显著差异(P=0.034),158V/V基因型CR减低,而FcγRⅡA、FcγRⅡB多态性与治疗反应无明显相关;④6例接受利妥昔单克隆抗体治疗的ITP患者,4例(67%)患者达CR,1例(17%)达PR,总治疗反应率高达84%,且无明显不良反应。结论:FcγRⅢA多态性,而不是FcγRⅡA、FcγRⅡB多态性,与ITP易感性及疗效相关。

This study was aimed to investigate the correlation ofFcγRpolymorphisms with the susceptibility,severity and efficacy of immunotherapy for patients with immune thrombocytopenia （ITP）. PCR and DNA sequencing were used to determine the polymorphisms of FcγRⅡA、FcγRⅢA and FcγRⅡB in 44 ITP patients, and in 97 healthy control subjects. The results indicated that FcγRⅢA-158V/F polymorphisms between patients and controls were control subjects. The results indicated that FcγRⅢA-158V/F polymorphisms between patients and controls were statistically significantly different （P = 0. 015 ） ; among FcyR IliA genotypes, the frequency of 158V/V homotype was higher in ITP （ P = 0.005 ）. However, the FcγRⅡA -131H/R or FcγRⅡB-232T/I polymorphisms were not significantly different between patients and controls; there were no correlation of FcγRⅡA、FcγRⅢA and FcγRⅡB genotype frequencies with the platelet counts or the courses of ITP; among the 38 ITP patients who received treatments, the complete response（CR） rate was 42% （16/38）, and partial response（PR） rate was 34% （13/38）. The therapeutic response was significantly different between FcγRⅢA-158V/V homotype and 158F/V heterotype （P = 0.034）. The CR of patients with 158V/V homotype was obviously lower than that of patients with 158F/V, but the frequencies of FcγRⅡA and FcγRⅡB genotypes not correlated with the responsiveness to treatment. The CR rate of 6 patients treated with rituximab was 67%, and PR rate was 17%. The overall response rate was as high as 84%, the adverse reactions were not observed. It is concluded that the polymorphism of FcγRⅢA -158V/F, but not FcγRⅡA-131H/R or FcγRⅡB- 232T/I, correlates with the patient susceptibility and therapeutic response of ITP.