HLA-DQA1^(*)05 correlates with increased risk of anti-drug antibody development and reduced response to infliximab in Chinese patients with Crohn’s disease  

作　　者：Wei Wang Qi Zhang Junzhang Zhao Tao Liu Jiayin Yao Xiang Peng Min Zhi Min Zhang 

机构地区：[1]Department of Gastroenterology,The Sixth Affiliated Hospital,Sun Yat-Sen University,Guangzhou,Guangdong 510655,P.R.China [2]Biomedical Innovation Center,The Sixth Affiliated Hospital,Sun Yat-Sen University,Guangzhou,Guangdong 510655,P.R.China

出　　处：《Gastroenterology Report》2024年第1期348-354,共7页胃肠病学报道(英文)

基　　金：funded by the China Crohn’s&Colitis Foundation[grant number CCCF-QF-2022A53-2].

摘　　要：Background:The efficacy of anti-TNF therapy in Crohn’s disease(CD),such as infliximab,is often compromised by the development of anti-drug antibodies(ADAs).The genetic variation HLA-DQA1*05 has been linked to the immunogenicity of biologics,influencing ADA formation.This study investigates the correlation between HLA-DQA1*05 and ADA formation in CD patients treated with inflixi-mab in a Chinese Han population and assesses clinical outcomes.Methods:In this retrospective cohort study,345 infliximab-exposed CD patients were genotyped for HLADQ A1*05A>G(rs2097432).We evaluated the risk of ADA development,loss of infliximab response,adverse events,and treatment discontinuation among vari-ant and wild-type allele individuals.Results:A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers(58.5%vs 42.9%,P=0.004).HLA-DQA1*05 carriage significantly increased the risk of ADAs development(adjusted hazard ratio=1.65,95%CI 1.18-2.30,P=0.003)and was associated with a greater likelihood of infliximab response loss(ad-justed HR=2.55,95%CI 1.78-3.68,P<0.0001)and treatment discontinuation(adjusted HR=2.21,95%CI 1.59-3.06,P<0.0001).Interestingly,combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers.Conclusions:HLA-DQA1*05 significantly predicts ADAs formation and impacts treatment outcomes in infliximab-treated CD patients.Pre-treatment screening for this genetic factor could therefore be instrumental in personalizing anti-TNF therapy strategies for these patients.

关 键 词：Crohn’s disease INFLIXIMAB HLA-DQA1*05 anti-drug antibodies 

分 类 号：R574.62[医药卫生—消化系统]