Tran Paul M H, Dong Fran, Satter Khaled Bin, Richardson Katherine P, Patel Roshni, Tran Lynn K H, Hopkins Diane, Kolhe Ravindra, Waugh Kathleen, Rewers Marian, Purohit Sharad
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th St., Augusta, GA 30912, USA.
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Mail Stop A-140, 1775 Aurora Court, Aurora, CO 80045, USA.
Endocrines. 2022 Sep;3(3):570-577. doi: 10.3390/endocrines3030048. Epub 2022 Sep 13.
Interleukin-1 antagonism is a proposed biomarker and potential therapy for the delay and/or treatment of type 1 diabetes (T1D). We evaluated the role of circulating interleukin-1 receptor antagonist (IL-1ra) in a prospectively monitored cohort of T1D patients. In order to determine a mechanistic association between IL-1ra and T1D, we performed co-localization analyses between serum IL-1ra protein quantitative trait loci and T1D genome-wide analysis studies. Adjusting for human leukocyte antigen (HLA) genotypes, first degree relative status, gender, and age, serum levels of IL-1ra were lower in subjects who progressed to T1D compared to the controls ( = 0.023). Our results suggest that females have higher levels of IL-1ra compared to males ( = 0.005). The 2q14.1 region associated with serum IL-1ra levels is not associated with a risk of developing T1D. Our data suggest that IL-1 antagonism by IL-1ra is not an effective therapy in T1D, but IL-1ra may be a biomarker for progression to T1D.
白细胞介素-1拮抗作用是一种针对1型糖尿病（T1D）延迟发病和/或治疗的潜在生物标志物及治疗方法。我们在一个前瞻性监测的T1D患者队列中评估了循环白细胞介素-1受体拮抗剂（IL-1ra）的作用。为了确定IL-1ra与T1D之间的机制关联，我们对血清IL-1ra蛋白质数量性状位点与T1D全基因组分析研究进行了共定位分析。在校正人类白细胞抗原（HLA）基因型、一级亲属关系、性别和年龄后，进展为T1D的受试者血清IL-1ra水平低于对照组（P = 0.023）。我们的结果表明，女性的IL-1ra水平高于男性（P = 0.005）。与血清IL-1ra水平相关的2q14.1区域与发生T1D的风险无关。我们的数据表明，IL-1ra介导的白细胞介素-1拮抗作用在T1D中并非有效治疗方法，但IL-1ra可能是T1D病情进展的生物标志物。
