[The relation between residual β-cell function and autoimmune status in long-term type 1 diabetes patients]

Objective: We aimed to investigate the autoimmune status of long-term type 1 diabetes mellitus (T1DM) patients with residual β-cell function. Methods: The residual β-cell function of long-term (disease duration≥10 years) autoimmune T1DM patients from the T1DM Integrated Management Clinic of the Second Xiangya Hospital was assessed by serum C-peptide levels. Patients with fasting or 2-hour postprandial C-peptide levels over the lower sensitivity limit of detection (16.7 pmol/L) were grouped as C-peptide-positive, and others were grouped as C-peptide-negative. We screened and enrolled all the C-peptide-positive patients (n=19). C-peptide-negative patients with matched sex, age, duration, BMI (n=19) and healthy controls (n=19) were recruited at the same time. The frequencies of CD4+T cell (Th1/Th2/Th17/Treg) and B cell (MZB/FoB/B10) subsets, the expression of PD-1/PD-L1 on T and B lymphocytes, and the levels of T1DM related cytokines including IFN-γ, TNF-α, IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-23 and IP-10 were tested. We compared these parameters in patients with different levels of β-cell function. Results: In healthy controls, C-peptide-negative and C-peptide-positive patients, the frequencies M (Q₁, Q₃) of Th1 cells were 9.93% (7.45%, 15.20%), 14.90% (11.70%, 18.00%) and 10.20% (6.93%, 15.80%) (P=0.015), and the frequencies M (Q₁, Q₃) of Treg cells were 3.52% (2.92%, 5.68%),2.88% (1.64%, 3.22%) and 3.12% (2.81%, 4.81%) (P=0.005), and the frequencies M(Q₁,Q₃) of PD-1+B cells were 4.69% (2.64%, 6.37%), 2.11% (1.45%, 3.63%) and 4.20% (2.53%, 6.01%) (P=0.003), respectively. The levels of IL-6 M(Q₁,Q₃)were 26.43(18.06, 33.35) ng/L, 42.97 (25.52, 66.30) ng/L, and 22.07 (14.85, 34.45) ng/L (P=0.006), and the levels of IP-10 M(Q₁,Q₃) were 107.39 (76.19, 126.07) ng/L, 188.82 (131.27, 348.18) ng/L and 128.26 (114.31, 136.50) ng/L (P<0.001) in healthy controls, C-peptide-negative and C-peptide-positive patients, respectively. Compared with C-peptide-positive patients, the frequency of Th1 cells and the levels of IL-6 and IP-10 cytokines were higher, while the frequencies of Treg cells and PD-1+B cells were lower in C-peptide-negative patients (all P<0.05). Conclusions: Long-term T1DM patients with residual β-cell function had lower frequency of Th1 cells, lower levels of IL-6, IP-10 cytokines, and higher frequencies of Treg and PD-1+B cells, which indicated a pronounced autoimmune tolerance.