Transcriptional Features Of Autoimmune Diabetes: Differentially Expressed Genes In Cd4+ And Cd8+ Subpopulations Of Blood T Cells

Latent autoimmune diabetes mellitus in adults (LADA) is considered an intermediate form between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), but the molecular mechanisms that explain its unique clinical and pathogenetic features remain poorly understood. Determination of differentially expressed genes (DEGs) in LADA compared to T1DM is necessary to develop more personalized approaches to diagnosis and therapy. To determine DEGs in peripheral blood mononuclear cells in patients with LADA compared with T1DM, and to assess the differences between these two groups and healthy volunteers. The study included 60 subjects (23 patients with T1DM for up to 1 year, 15 patients with LADA for up to 5 years, and 22 healthy volunteers). The average age of patients with LADA was 40 [34; 45] years, with T1DM — 26 [21; 31] years. The design was a cross-sectional, observational, single-center study. Peripheral blood mononuclear cells were isolated from all participants, and single-cell RNA sequencing (scRNA-seq) was performed. Differential gene expression analysis was performed using the “pseudo-beam” approach (pyDEseq2, p<0.05 adjusted for multiple comparisons, |log2FoldChange|≥0.5). Statistical analysis was performed using nonparametric criteria (Kruskal–Wallis, Mann–Whitney). In LADA patients, decreased expression of HLA-G, SPARC and C20orf204 and increased expression of AC002460.2 were found in CD4+ naive T cells compared to healthy volunteers (p<0.05). In the T1DM group, the main differences concerned central memory CD4+ T cells (IFIT1, CASP3, LAMP3, HIST1H2BN). When comparing LADA and T1DM, only one gene (C20orf204, p<0.05) was statistically significantly different in CD4+ naive T cells. The obtained data indicate the similarity of molecular genetic patterns of LADA and T1DM. Patients with LADA show moderate changes in the expression of a number of genes associated with immune regulation and inflammation. Minimal differences between these forms of diabetes emphasize the similarity of pathogenesis.