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

Area of Science:

• Immunology
• Endocrinology
• Type 1 Diabetes Mellitus Research

Background:

• Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic beta cells.
• Residual beta-cell function, indicated by C-peptide levels, can persist for years in some T1DM patients.
• The autoimmune status and immune cell profiles in long-term T1DM patients with residual function require further investigation.

Purpose of the Study:

• To investigate the autoimmune status of long-term T1DM patients who retain some beta-cell function.
• To compare immune cell subsets (T cells, B cells) and cytokine levels between T1DM patients with and without residual beta-cell function, and healthy controls.
• To explore the relationship between residual beta-cell function and immune tolerance markers.

Main Methods:

• Recruited long-term (≥10 years) T1DM patients categorized as C-peptide-positive (residual function) or C-peptide-negative.
• Included matched C-peptide-negative T1DM patients and healthy controls for comparison.
• Assessed frequencies of CD4+ T cell subsets (Th1, Th2, Th17, Treg) and B cell subsets (MZB, FoB, B10).
• Measured expression of PD-1/PD-L1 on lymphocytes and levels of T1DM-related cytokines (e.g., IL-6, IP-10).

Main Results:

• C-peptide-positive T1DM patients exhibited a lower frequency of Th1 cells and higher frequencies of Treg cells compared to C-peptide-negative patients.
• Levels of IL-6 and IP-10 cytokines were significantly lower in C-peptide-positive T1DM patients compared to C-peptide-negative patients.
• Frequencies of PD-1 positive B cells were higher in C-peptide-positive T1DM patients compared to C-peptide-negative patients.

Conclusions:

• Long-term T1DM patients with residual beta-cell function demonstrate characteristics of pronounced autoimmune tolerance.
• The observed immune profiles (lower Th1, higher Treg, altered B cells, specific cytokine patterns) suggest a shift towards immune regulation.
• These findings highlight distinct immunological states in T1DM based on residual beta-cell function.