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抗环瓜氨酸肽抗体和类风湿因子同种型与 HLA-DRB1 共享表位等位基因在埃及类风湿关节炎患者中的相关性。

Association of anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes with HLA-DRB1 shared epitope alleles in Egyptian rheumatoid arthritis patients.

机构信息

Internal Medicine Department, National Research Center, Cairo, Egypt.

Clinical and Chemical Pathology Department, National Research Center, Cairo, Egypt.

出版信息

Int J Rheum Dis. 2020 May;23(5):647-653. doi: 10.1111/1756-185X.13819. Epub 2020 Mar 13.

Abstract

INTRODUCTION

The most common genetic risk factor for rheumatoid arthritis (RA) is human leucocyte antigen DRB1 (HLA-DRB1) shared epitope (SE).

AIM

To investigate the relationship between anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), immunoglobulin (Ig)G, IgM and IgA and HLA-DRB1 SE among Egyptian patients with RA.

METHODS

Serum levels of anti-CCP antibodies and RFIgG, RFIgM, RFIgA were assayed using enzyme-linked immunosorbent assay for 157 Egyptian RA patients and 150 healthy controls attending the outpatient clinics of National Research Center and Kasr El Aini Hospital. HLA-DRB1 genotyping was performed by the DynalAllSetTM polymerase chain reaction (PCR) single specific primer low-resolution typing kits. Amplified PCR product was checked using 3% agarose gel.

RESULTS

HLA-DRB1-SE was found among 129 (82.2%) RA patients and 67 (44.7%) controls (odds ratio [OR] 5.7, CI 3.4-9.6, P < .0001). The risk of RA development was higher with the presence of SE two alleles (OR 11.6, P < .0001), while the OR for 1 copy SE allele was 4.4 (P < .0001). HLA-DRB1-SE was significantly associated with positive as well as negative anti-CCP and RF isotypes. The stronger association was with anti-CCP positivity with OR 11 (5.1-23.6), P < .0001. Furthermore, the risk of development of positive anti-CCP and RF isotypes was higher with the presence of 2 copies of SE alleles than with 1 copy.

CONCLUSION

The prevalence of HLA-DRB1-SE is high in Egyptian RA patients. The role of SE in RA patients is most probably related to the development of anti-CCP positive RA rather than the development of anti-CCP positivity.

摘要

简介

类风湿关节炎(RA)最常见的遗传风险因素是人类白细胞抗原 DRB1(HLA-DRB1)共享表位(SE)。

目的

研究埃及 RA 患者抗环瓜氨酸肽(抗-CCP)、类风湿因子(RF)、免疫球蛋白(Ig)G、IgM 和 IgA 与 HLA-DRB1 SE 之间的关系。

方法

采用酶联免疫吸附试验检测 157 例埃及 RA 患者和 150 例门诊就诊的健康对照者血清抗-CCP 抗体及 RF IgG、RF IgM、RF IgA 水平。采用 DynalAllSetTM 聚合酶链反应(PCR)单特异性引物低分辨率基因分型试剂盒进行 HLA-DRB1 基因分型。扩增的 PCR 产物用 3%琼脂糖凝胶检查。

结果

在 129 例(82.2%)RA 患者和 67 例(44.7%)对照者中发现 HLA-DRB1-SE(比值比 [OR] 5.7,95%置信区间 [CI] 3.4-9.6,P<0.0001)。存在 SE 两个等位基因时,RA 发病风险更高(OR 11.6,P<0.0001),而 SE 等位基因 1 拷贝时 OR 为 4.4(P<0.0001)。HLA-DRB1-SE 与抗-CCP 及 RF 同型均呈显著正相关。与抗-CCP 阳性的相关性更强,OR 为 11(5.1-23.6),P<0.0001。此外,与 SE 等位基因 1 拷贝相比,SE 等位基因 2 拷贝存在时,阳性抗-CCP 和 RF 同型的发病风险更高。

结论

埃及 RA 患者 HLA-DRB1-SE 患病率较高。SE 在 RA 患者中的作用可能与抗-CCP 阳性 RA 的发生有关,而不是与抗-CCP 阳性的发生有关。

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