Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

10.1038/12465 ◽  
1999 ◽  
Vol 5 (9) ◽  
pp. 1026-1031 ◽  
Author(s):  
F. Susan Wong ◽  
Jaana Karttunen ◽  
Caroline Dumont ◽  
Li Wen ◽  
Irene Visintin ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cdna Library ◽  
Mhc Class I ◽  
Class I ◽  
Organ Specific

Association between the transmembrane region polymorphism of MHC class I chain related Gene-A and type 1 diabetes mellitus in Sweden

2003 ◽  
Vol 64 (5) ◽  
pp. 553-561 ◽  
Author(s):  
Manu Gupta ◽  
Liene Nikitina-Zake ◽  
Marjan Zarghami ◽  
Mona Landin-Olsson ◽  
Ingrid Kockum ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Mhc Class I ◽  
Class I ◽  
Related Gene ◽  
Transmembrane Region

scholarly journals The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, non-toxic concentrations of interleukin 1 β

2019 ◽  
Author(s):  
Muhammad Saad Khilji ◽  
Danielle Verstappen ◽  
Tina Dahlby ◽  
Michala Cecilie Burstein Prause ◽  
Celina Pihl ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mhc Class I ◽  
Pancreatic Beta Cells ◽  
Interleukin 1 ◽  
Class I ◽  
Β Cells ◽  
Autoimmune Attack ◽  
Active Intermediate ◽  
Toxic Concentrations

AbstractA central and still open question regarding the pathogenesis of autoimmune diseases, such as type 1 diabetes, concerns the processes that underlie the generation of MHC-presented autoantigenic epitopes that become targets of autoimmune attack. Proteasomal degradation is a key step in processing of proteins for MHC class I presentation. Different types of proteasomes can be expressed in cells dictating the repertoire of peptides presented by the MHC class I complex. Of particular interest for type 1 diabetes is the proteasomal configuration of pancreatic β cells, as this might facilitate autoantigen presentation by β cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in β cells, regulated by inflammatory signals and participate in the formation of active intermediate or immuno-proteasomes.We show that inducible proteasomal subunits are constitutively expressed in human and rodent islets and an insulin-secreting cell-line. Moreover, the β5i subunit is incorporated into active intermediate proteasomes that are bound to 19S or 11S regulatory particles. Finally, inducible subunit expression along with increase in total proteasome activities are further upregulated by non-toxic concentrations of IL-1β stimulating proinsulin biosynthesis. These findings suggest that the β cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.

MHC Class I Chain-Related Gene Alleles 5 and 5.1 Are Transmitted More Frequently to Type 1 Diabetes Offspring in HBDI Families

2006 ◽  
Vol 958 (1) ◽  
pp. 309-311 ◽  
Author(s):  
L. NIKITINA ZAKE ◽  
M. GHADERI ◽  
Y. S. PARK ◽  
S. BABU ◽  
G. EISENBARTH ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mhc Class I ◽  
Class I ◽  
Related Gene ◽  
Diabetes Offspring

MHC Class I Chain-Related Gene-A Is Associated with IA2 and IAA but Not GAD in Swedish Type 1 Diabetes Mellitus

2006 ◽  
Vol 1079 (1) ◽  
pp. 229-239 ◽  
Author(s):  
M. GUPTA ◽  
J. GRAHAM ◽  
B. MCNEENY ◽  
M. ZARGHAMI ◽  
M. LANDIN-OLSSON ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Mhc Class I ◽  
Class I ◽  
Related Gene

scholarly journals Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

Nature ◽  
2007 ◽  
Vol 450 (7171) ◽  
pp. 887-892 ◽  
Author(s):  
Sergey Nejentsev ◽  
◽  
Joanna M. M. Howson ◽  
Neil M. Walker ◽  
Jeffrey Szeszko ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mhc Class I ◽  
Class I ◽  
Diabetes Susceptibility

scholarly journals HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Ziyu Jiang ◽  
Wenqian Ren ◽  
Hua Liang ◽  
Jinhua Yan ◽  
Daizhi Yang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Risk ◽  
Hla Class I ◽  
Class I ◽  
Chinese Patients ◽  
Onset Age ◽  
Disease Heterogeneity ◽  
Negatively Associated ◽  
Healthy Control

Abstract Aims/hypothesis The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes. Methods A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing. Results The susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. Conclusions/interpretation In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies. Graphical abstract

scholarly journals CTLA-4 (+49A/G) Polymorphism in Type 1 Diabetes Children of Sudanese Population

2021 ◽  
Vol 08 (01) ◽  
pp. 011-018
Author(s):  
Khalid E. Khalid Kheiralla
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Ethylenediaminetetraacetic Acid ◽  
Negative Regulator ◽  
Cytotoxic Lymphocyte ◽  
Pediatric Clinic ◽  
Homozygous Genotype ◽  
Organ Specific ◽  
Α Helix

Abstract Background Type 1 diabetes mellitus (T1DM) is an organ-specific T cell-mediated autoimmune disease, characterized by destruction of pancreatic islets. Cytotoxic lymphocyte antigen-4 (CTLA-4) is a negative regulator of T cell proliferation, thus conferring susceptibility to autoimmunity. Aims This study aimed to investigate the association of CTLA-4 +49A/G (rs231775) polymorphism with a risk of T1DM in Sudanese children. Methods This a case–control study included 100 children with T1DM, referred to the pediatric clinic at referral pediatric teaching hospital in Gezira State-Sudan. Hundred unrelated healthy controls were recruited from departments in the same hospital. Genomic deoxyribonucleic acid (DNA) was extracted from Ethylenediaminetetraacetic Acid (EDTA)-preserved blood using QIAamp DNA Blood Mini Kit (QIAamp Blood) (QIAGEN; Valencia, CA). The polymerase chain reaction PCR restriction fragment length polymorphism (PCR-RFLP) and sequencing were applied for the CTLA-4 (+49A/G) genotyping. The changes accompanied the polymorphism were evaluated using relevant bioinformatics tools. Results The genotype and allele frequencies of the CTLA-4 (+49A/G) polymorphism were significantly different between the patients and controls (p = 0.00013 and 0.0002, respectively). In particular, the frequency of the G allele, GG homozygous genotype, and AG heterozygous genotype were significantly increased in patients than in controls ([28% versus 7%, odds ratio (OR) = 5.16, 95% confidence interval [CI] = 2.77–9.65, p = 0.00] [12% versus 2%, OR = 6.68, CI = 1.46–30.69, p = 0.01] [32% versus 10%, OR = 4.24, CI = 1.95–9.21, p = 0.00], respectively). The presence of the G allele (homozygous) showed an influence on the signal peptide polarity, hydrophobicity, and α-helix propensity of the CTLA-protein. Conclusion The results further support the association of CTLA-4 (+49A/G) polymorphism and the risk of T1DM in our study population.

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