八例免疫检查点抑制剂相关糖尿病临床特征及人类白细胞抗原基因型分析  

Clinical characteristics and HLA genotype analysis of 8 cases of immune checkpoint inhibitor associated diabetes mellitus

作　　者：刘怡晨 赵立玲[1] 刘红 陈科[1] 金萍[1] LIU Yichen;ZHAO Liling;LIU Hong;JIN Ping(Department of Endocrinology,The Third Xiangya Hospital of Central South University,Changsha 410007,China)

机构地区：[1]中南大学湘雅三医院内分泌科,长沙410007

出　　处：《中国糖尿病杂志》2022年第7期522-527,共6页Chinese Journal of Diabetes

基　　金：国家自然科学基金(81670730);湖南省自然科学基金(2021JJ31007);湖南省卫生健康委员会科研计划课题(202103061081);湖南省三诺糖尿病公益基金会(2020SD09)。

摘　　要：目的 分析免疫检查点抑制剂(ICIs)相关DM临床特征及人类白细胞抗原(HLA)基因型。方法 选取2021年1月至2022年1月于中南大学湘雅三医院内分泌科治疗的ICIs相关DM患者8例,采用放射配体法检测胰岛自身抗体,PCR-顺序特异寡核苷酸技术进行HLA基因型分析。结果 8例男性患者平均年龄(58.75±7.67)岁,在接受ICIs治疗后(5.13±2.23)个疗程发病。2例患者以DKA起病,4例以糖尿病酮症起病。平均HbA1c(9.69±2.38)%,FC-P(0.54±0.49)ng/ml,餐后C-P(0.85±0.68)ng/ml。75%(6/8)的患者携带T1DM易感单体型(DRB1*04:05-DQB1*03:01、DRB1*09:01-DQB1*03:03及DRB1*04:05-DQB1*04:01),50%(4/8)的患者携带T1DM保护性单体型(DRB1*11:01-DQB1*03:02及DRB1*12:02-DQB1*03:01),所有患者胰岛自身抗体阴性,均接受胰岛素治疗。结论 ICIs相关DM起病急,胰岛功能差,依赖胰岛素治疗,胰岛自身抗体阳性率低,同时携带T1DM的HLA易感及保护性单体型提示其发病机制与T1DM不同,是一种新的DM类型。Objective To investigate the clinical characteristics and HLA genotypes of immune checkpoint inhibitor(ICIs)related diabetes mellitus.Methods Eight patients with ICIs related DM treated in the Department of Endocrinology of Xiangya Third Hospital of Central South University from January 2021to January 2022 were selected. Islet autoantibodies were detected by radioligand assay. HLA genotypes were analyzed by PCR-sequence specific oligonucleotide technique.Results All patients were male,with an average age of(58. 75±7. 67)years,average HbA1c(9. 69±2. 38)%,asting c-peptide(0. 54±0. 49)ng/ml,postprandial C-peptide was(0. 85±0. 68)ng/ml,and negative islet autoantibodies. Diabetes developed after(5. 13 ± 2. 23)courses of ICIs treatment. Two patients presented with DKA at onset,and four patients presented with diabetic ketosis. 75%(6/8)of patients had type 1 diabetes mellitus(T1DM)-susceptible HLA haplotypes(DRB1*04:05-DQB1*03:01,DRB1*09:01-DQB1*03:03,DRB1*04:05-DQB1*04:01). 50%(4/8)of patients had T1DM-protective haplotype(DRB1*11:01-DQB1*03:02 and DRB1*12:02-DQB1*03:01). All 8 patients received insulin therapy.Conclusion The characteristics of acute onset,poor islet function,dependence on insulin therapy,low positive rate of insulin autoantibodies and carrying both T1DMassociated HLA susceptible and protective haplotypes indicated that the pathogenesis of ICIs related diabetes is different from that of T1DM,which may be a new type of diabetes.

关 键 词：免疫检查点抑制剂 糖尿病 HLA基因型 

分 类 号：R587.1[医药卫生—内分泌]