皮下注射阿巴西普治疗新发1型糖尿病：临床及免疫学效应

Subcutaneous Abatacept in New Onset Type 1 Diabetes: Clinical and Immunological Effects.

作者信息

Jerram Samuel T, Yang Jennie H M, Williams Evangelia, Domingo-Vila Clara, Liu Yuk-Fun, Peakman Mark, Leslie R David, Tree Timothy

机构信息

Blizard Institute, Queen Mary, University of London, London, UK.

Wolfson Diabetes and Endocrine Clinic, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

出版信息

Diabetes Metab Res Rev. 2025 Sep;41(6):e70074. doi: 10.1002/dmrr.70074.

DOI:10.1002/dmrr.70074

PMID:40790833

Abstract

Abatacept is a CTLA4-Ig fusion protein that blocks CD80/CD86-dependent T-cell co-stimulation. When administered, Abatacept limits, to a variable degree, loss of stimulated C-peptide secretion in patients with newly-diagnosed type 1 diabetes (T1D), while reducing both circulating memory CD4 T-cells and T follicular helper (Tfh) cells; however, its precise mechanism of action is not known. To investigate this effect, we studied 12 patients, using multi-parameter flow cytometry, who each self-administered Abatacept in subcutaneous formulation for 6 months within 100 days of diagnosis. Abatacept treatment impacted the CD4 T cell memory compartment, inducing a reduction in T-effector cells across both conventional (Tconv) and regulatory (Treg) sub-populations. A reduction in activated Tfh cells (CXCR5PD1ICOS), previously described with intravenous therapy, was replicated and extended. An integrated baseline immunological phenotype predicted Abatacept-induced preservation of C-peptide.

摘要

阿巴西普是一种CTLA4-Ig融合蛋白，可阻断CD80/CD86依赖性T细胞共刺激。给药后，阿巴西普在不同程度上限制新诊断的1型糖尿病（T1D）患者受刺激的C肽分泌丧失，同时减少循环记忆CD4 T细胞和T滤泡辅助（Tfh）细胞；然而，其确切作用机制尚不清楚。为了研究这种效应，我们使用多参数流式细胞术对12例患者进行了研究，这些患者在诊断后100天内自行皮下注射阿巴西普6个月。阿巴西普治疗影响了CD4 T细胞记忆区室，导致传统（Tconv）和调节（Treg）亚群中的T效应细胞减少。先前静脉内治疗中描述的活化Tfh细胞（CXCR5PD1ICOS）减少得以重现并扩展。综合的基线免疫表型可预测阿巴西普诱导的C肽保留情况。