Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cells
BACKGROUND: Latent autoimmune diabetes in adults (LADA) is considered an intermediate form between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying its unique clinical and pathogenetic features remain insufficiently studied. Identifying differentially e...
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Endocrinology Research Centre
2025-05-01
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| Online Access: | https://www.dia-endojournals.ru/jour/article/view/13316 |
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| author | I. I. Golodnikov E. S. Podshivalova V. I. Chechekhin A. V. Zubritsky A. A. Matrosova Y. V. Dvoryanchikov M. D. Samsonova E. K. Markelova Y. A. Medvedeva T. V. Nikonova E. V. Bondarenko S. V. Popov I. R. Minniakhmetov M. V. Shestakova |
| author_facet | I. I. Golodnikov E. S. Podshivalova V. I. Chechekhin A. V. Zubritsky A. A. Matrosova Y. V. Dvoryanchikov M. D. Samsonova E. K. Markelova Y. A. Medvedeva T. V. Nikonova E. V. Bondarenko S. V. Popov I. R. Minniakhmetov M. V. Shestakova |
| author_sort | I. I. Golodnikov |
| collection | DOAJ |
| description | BACKGROUND: Latent autoimmune diabetes in adults (LADA) is considered an intermediate form between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying its unique clinical and pathogenetic features remain insufficiently studied. Identifying differentially expressed genes (DEGs) in LADA compared to T1DM is essential for developing more personalized diagnostic and therapeutic approaches.OBJECTIVE: To identify DEGs in peripheral blood mononuclear cells (PBMCs) of patients with LADA compared to those with T1DM, and to evaluate differences in DEGs between these patient groups and healthy volunteers.MATERIALS AND METHODS: The study included 60 participants (23 T1DM patients with disease duration of up to 1 year, 15 LADA patients with disease duration of up to 5 years, and 22 healthy volunteers). The median age of LADA patients was 40 [34; 45] years, and for T1DM patients, 26 [21; 31] years. This was a single-center, cross-sectional observational study. PBMCs were isolated from all participants, and single-cell RNA sequencing (scRNA-seq) was performed. Differential gene expression analysis was conducted using a pseudo-bulk approach (pyDEseq2, p<0.05 adjusted for multiple comparisons, |log2FoldChange| ≥0.5). Statistical analyses employed nonparametric tests (Kruskal–Wallis, Mann–Whitney).RESULTS: In LADA patients, reduced expression of HLA-G, SPARC, and C20orf204 and increased expression of AC002460.2 were observed compared to healthy volunteers (p<0.05) in CD4+ Naive T-cells. In the T1DM group, the most significant differences were identified in CD4+ Central memory T-cells (IFIT1, CASP3, LAMP3, HIST1H2BN). When comparing LADA to T1DM, only one transcript, C20orf204, showed statistically significant differential expression (p<0.05) in CD4+ Naive T-cells.CONCLUSION: The findings indicate that LADA and T1DM share similar molecular patterns, with LADA exhibiting moderate changes in the expression of genes associated with immune regulation and inflammation. The minimal differences between these forms of diabetes highlight their pathogenetic similarity. |
| format | Article |
| id | doaj-art-2d57b502996445588f5e6eed4849c2b4 |
| institution | OA Journals |
| issn | 2072-0351 2072-0378 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Endocrinology Research Centre |
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| series | Сахарный диабет |
| spelling | doaj-art-2d57b502996445588f5e6eed4849c2b42025-08-20T01:57:15ZengEndocrinology Research CentreСахарный диабет2072-03512072-03782025-05-0128212413510.14341/DM1331611150Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cellsI. I. Golodnikov0E. S. Podshivalova1V. I. Chechekhin2A. V. Zubritsky3A. A. Matrosova4Y. V. Dvoryanchikov5M. D. Samsonova6E. K. Markelova7Y. A. Medvedeva8T. V. Nikonova9E. V. Bondarenko10S. V. Popov11I. R. Minniakhmetov12M. V. Shestakova13Endocrinology Research CentreEndocrinology Research CentreEndocrinology Research Centre; Lomonosov Moscow State UniversityFederal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of SciencesEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreFederal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of SciencesEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreBACKGROUND: Latent autoimmune diabetes in adults (LADA) is considered an intermediate form between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying its unique clinical and pathogenetic features remain insufficiently studied. Identifying differentially expressed genes (DEGs) in LADA compared to T1DM is essential for developing more personalized diagnostic and therapeutic approaches.OBJECTIVE: To identify DEGs in peripheral blood mononuclear cells (PBMCs) of patients with LADA compared to those with T1DM, and to evaluate differences in DEGs between these patient groups and healthy volunteers.MATERIALS AND METHODS: The study included 60 participants (23 T1DM patients with disease duration of up to 1 year, 15 LADA patients with disease duration of up to 5 years, and 22 healthy volunteers). The median age of LADA patients was 40 [34; 45] years, and for T1DM patients, 26 [21; 31] years. This was a single-center, cross-sectional observational study. PBMCs were isolated from all participants, and single-cell RNA sequencing (scRNA-seq) was performed. Differential gene expression analysis was conducted using a pseudo-bulk approach (pyDEseq2, p<0.05 adjusted for multiple comparisons, |log2FoldChange| ≥0.5). Statistical analyses employed nonparametric tests (Kruskal–Wallis, Mann–Whitney).RESULTS: In LADA patients, reduced expression of HLA-G, SPARC, and C20orf204 and increased expression of AC002460.2 were observed compared to healthy volunteers (p<0.05) in CD4+ Naive T-cells. In the T1DM group, the most significant differences were identified in CD4+ Central memory T-cells (IFIT1, CASP3, LAMP3, HIST1H2BN). When comparing LADA to T1DM, only one transcript, C20orf204, showed statistically significant differential expression (p<0.05) in CD4+ Naive T-cells.CONCLUSION: The findings indicate that LADA and T1DM share similar molecular patterns, with LADA exhibiting moderate changes in the expression of genes associated with immune regulation and inflammation. The minimal differences between these forms of diabetes highlight their pathogenetic similarity.https://www.dia-endojournals.ru/jour/article/view/13316diabetes mellitus, type 1latent autoimmune diabetes in adultsgene expression profilingsingle cell rna sequencingcd4-positive t-lymphocytescd8-positive t-lymphocytesautoimmunity |
| spellingShingle | I. I. Golodnikov E. S. Podshivalova V. I. Chechekhin A. V. Zubritsky A. A. Matrosova Y. V. Dvoryanchikov M. D. Samsonova E. K. Markelova Y. A. Medvedeva T. V. Nikonova E. V. Bondarenko S. V. Popov I. R. Minniakhmetov M. V. Shestakova Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cells Сахарный диабет diabetes mellitus, type 1 latent autoimmune diabetes in adults gene expression profiling single cell rna sequencing cd4-positive t-lymphocytes cd8-positive t-lymphocytes autoimmunity |
| title | Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cells |
| title_full | Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cells |
| title_fullStr | Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cells |
| title_full_unstemmed | Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cells |
| title_short | Transcriptional features of autoimmune diabetes: differentially expressed genes in CD4+ and CD8+ subpopulations of blood T cells |
| title_sort | transcriptional features of autoimmune diabetes differentially expressed genes in cd4 and cd8 subpopulations of blood t cells |
| topic | diabetes mellitus, type 1 latent autoimmune diabetes in adults gene expression profiling single cell rna sequencing cd4-positive t-lymphocytes cd8-positive t-lymphocytes autoimmunity |
| url | https://www.dia-endojournals.ru/jour/article/view/13316 |
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