Immunoglobulin G Fc-receptor (FcgammaR) IIA and IIIB polymorphisms related to disability in MS.
Immunoglobulin G Fc-receptor (FcgammaR) IIA and IIIB polymorphisms related to disability in MS.
复制标题
免疫球蛋白 G Fc 受体 (FcgammaR) IIA 和 IIIB 多态性与 MS 残疾相关。
作者：
K. Myhr;G. Raknes;H. Nyland;C. Vedeler
目的
MS是免疫介导的遗传易感个体。免疫球蛋白G（IgG）的Fc片段的受体（Fc γ R）通过将免疫复合物靶向效应细胞来连接体液和细胞免疫应答。不同的Fc γ R在其分布、强度和结合不同IgG亚类的能力方面显示出可变性。
方法
为了研究FcgammaR在MS中的作用，对136例MS患者和96例匹配的对照进行了FcgammaRIIA和FcgammaRIIIB基因多态性的基因分型;结果与扩展残疾状态量表（EDSS）测量的疾病易感性和严重程度相关。
结果
Fc γ RIIA和Fc γ RIIIB的等位基因频率在MS患者和对照组之间没有显著差异。Fc γ RIIIB中性粒细胞抗原（NA）1等位基因纯合子患者比Fc γ RIIIB NA 2等位基因杂合子或纯合子患者具有更明显的良性MS病程。Fc γ RIIA组氨酸（H）等位基因纯合子患者的MS病程也比Fc γ RIIA精氨酸（R）等位基因杂合子或纯合子患者的MS病程更良性。
结论
结果表明Fc γ RIIIB和Fc γ RIIA在较小程度上是MS中的疾病修饰基因。Fc γ RIIIB NA 1/NA 1和Fc γ RIIA H/H分别比Fc γ RIIIB NA 2/NA 2和Fc γ RIIA R/R更有效地结合IgG 1/IgG 3和IgG 2亚类。更有效地处理循环免疫复合物可能是MS临床结局更好的机制之一。
OBJECTIVE
MS is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of immunoglobulin G (IgG) (FcgammaR) link the humoral and cellular immune responses by targeting immune complexes to effector cells. Different FcgammaR show variability in their distribution, strength, and capacity of binding different IgG subclasses.
METHODS
To investigate the role of FcgammaR in MS, 136 MS patients and 96 matched controls were genotyped for FcgammaRIIA and FcgammaRIIIB gene polymorphisms; the results were correlated to disease susceptibility and severity measured by the Expanded Disability Status Scale (EDSS).
RESULTS
The allele frequencies of the FcgammaRIIA and FcgammaRIIIB did not differ significantly between the MS patients and the controls. Patients homozygous for the FcgammaRIIIB neutrophil antigen (NA) 1 allele had a significantly more benign course of MS than patients heterozygous or homozygous for the FcgammaRIIIB NA2 allele. Patients homozygous for the FcgammaRIIA histidine (H) allele also had a more benign course of MS than patients heterozygous or homozygous for the FcgammaRIIA arginine (R) allele.
CONCLUSION
The results implicate FcgammaRIIIB and to a lesser extent FcgammaRIIA as disease-modifying genes in MS. FcgammaRIIIB NA1/NA1 and FcgammaRIIA H/H bind more efficient IgG1/IgG3 and IgG2 subclasses, respectively, than FcgammaRIIIB NA2/NA2 and FcgammaRIIA R/R. A more effective processing of circulating immune complexes may be one mechanism for better clinical outcome in MS.