Shared and distinct genetics of pure type 1 diabetes and type 1 diabetes with celiac disease, homology in their auto-antigens and immune dysregulation states: a study from North India.
Acta Diabetol
; 61(6): 791-805, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38483572
ABSTRACT
AIM:
This study was undertaken to explicate the shared and distinctive genetic susceptibility and immune dysfunction in patients with T1D alone and T1D with CD (T1D + CD).METHODS:
A total of 100 T1D, 50 T1D + CD and 150 healthy controls were recruited. HLA-DRB1/DQB1 alleles were determined by PCR-sequence-specific primer method, SNP genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP-array and genotyping for INS-23 Hph1 A/T was done by RFLP. Autoantibodies and cytokine estimation was done by ELISA. Immune-regulation was analysed by flow-cytometry. Clustering of autoantigen epitopes was done by epitope cluster analytical tool.RESULTS:
Both T1D alone and T1D + CD had a shared association of DRB1*0301, DRB1*04, DRB3*0107/15 and DQB1*02. DRB3*0107/15 confers the highest risk for T1D with relative risk of 11.32 (5.74-22.31). Non-HLA gene polymorphisms PTPN22 and INS could discriminate between T1D and T1D + CD. T1D + CD have significantly higher titers of autoantibodies, expression of costimulatory molecules on CD4 and CD8 cells, and cytokine IL-17A and TGF-ß1 levels compared to T1D patients. Epitopes from immunodominant regions of autoantigens of T1D and CD clustered together with 40% homology.CONCLUSION:
Same HLA genes provide susceptibility for both T1D and CD. Non-HLA genes CTLA4, PTPN22 and INS provide further susceptibility while different polymorphisms in PTPN22 and INS can discriminate between T1D and T1D + CD. Epitope homology between autoantigens of two diseases further encourages the two diseases to occur together. The T1D + CD being more common in females along with co-existence of thyroid autoimmunity, and have more immune dysregulated state than T1D alone.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Doença Celíaca
/
Predisposição Genética para Doença
/
Diabetes Mellitus Tipo 1
/
Proteína Tirosina Fosfatase não Receptora Tipo 22
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Acta Diabetol
/
Acta diabetol
/
Acta diabetologica
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia
País de publicação:
Alemanha