摘要目的:调查血清抗中性粒细胞胞质抗体(antineutrophil cytoplasmic antibody, ANCA)阳性在服用抗甲状腺药物的Graves病人群中的流行情况及相关影响因素，并探讨CD18 rs235326、HLA-DRB1*09∶01、HLA-DQB1*03∶01基因多态性与血清ANCA阳性的相关性。方法:收集2020年9月至2021年12月于广东省人民医院就诊的Graves病患者的临床及实验室检查数据进行横断面分析，并从中选取年龄、性别匹配的血清ANCA阳性及阴性患者对上述基因位点进行测序。结果:共有173例患者纳入最终分析，其中ANCA阳性患者42例(24.28%)，ANCA阴性患者131例(75.72%)。ANCA阳性患者诊断后病程及服药疗程均显著较ANCA阴性组患者长( P<0.001)。在ANCA阳性患者中，71.43%患者均服用过甲巯咪唑及丙硫氧嘧啶，而在ANCA阴性组，66.41%患者仅服用甲巯咪唑( P<0.001)。各有24例ANCA阳性和25例阴性患者进行基因检测，CD18 rs235326基因多态性在2组间无显著差异，HLA-DRB1*09∶01 rs17886918( P＝0.005)、rs9269959( P＝0.002)和HLA-DQB1*03∶01 rs1130399( P＝0.016)、rs1140317( P＝0.029)在2组间等位基因分布存在差异。多因素 logistic回归分析显示仅HLA-DRB1*09∶01 rs17886918与血清ANCA阳性呈独立相关( P＝0.005)。 结论:Graves病患者服用抗甲状腺药物期间出现ANCA阳性与更长的诊断后病程及服药疗程相关。位于HLA-DRB1*09∶01上的rs17886918基因多态性可能与ANCA阳性相关。

abstractsObjective:To investigate the prevalence and related factors of serum antineutrophil cytoplasmic antibody(ANCA) positivity in Graves′ disease patients receiving antithyroid drugs, and to explore the correlation of CD18 rs235326, HLA-DRB1*09∶01, and HLA-DQB1*03∶01 gene polymorphisms with serum ANCA positivity.Methods:Clinical and laboratory data of Graves′ disease patients who visited Guangdong Provincial People′s Hospital from September 2020 to December 2021 were collected for a cross-sectional analysis. Serum ANCA-positive and ANCA-negative patients matched for age and gender were selected for sequencing of the aforementioned gene loci.Results:A total of 173 patients were included in the final analysis. Among them, 42 patients(24.28%) were ANCA-positive, while 131 patients(75.72%) were negative. The disease duration and medication treatment duration in ANCA-positive patients was significantly longer compared to ANCA-negative patients( P<0.001). In the ANCA-positive group, 71.43% of patients had taken both propylthiouracil and methimazole, while in the ANCA-negative group, 66.41% of patients had only taken methimazole( P<0.001). Gene sequencing was performed on 24 ANCA-positive and 25 ANCA-negative patients, respectively. There was no significant difference in CD18 rs235326 gene polymorphism between the two groups, but there were allele distribution differences in rs17886918( P=0.005) and rs9269959 ( P=0.002) of HLA-DRB1*09∶01, as well as rs1130399( P=0.016) and rs1140317( P=0.029) of HLA-DQB1*03∶01. Multivariate logistic regression analysis showed that only rs17886918 of HLA-DRB1* 09∶01 was independently associated with serum ANCA positivity( P=0.005). Conclusion:The presence of ANCA positivity during the administration of anti-thyroid drugs in patients with Graves′ disease is associated with longer disease duration and medication treatment duration. Gene polymorphism of HLA-DRB1*09∶01 rs17886918 may be associated with ANCA positivity.