HLA Class II Differentiates Between Thyroid and Polyglandular Autoimmunity

2015 ◽  
Vol 48 (04) ◽  
pp. 232-237 ◽  
Author(s):  
S. Barkia Beradhi ◽  
B. Flesch ◽  
M. Hansen ◽  
N. Matheis ◽  
G. Kahaly
2019 ◽  
Vol 105 (6) ◽  
pp. 1737-1747 ◽  
Author(s):  
Lara Frommer ◽  
Brigitte K Flesch ◽  
Jochem König ◽  
George J Kahaly

Abstract Context The structure of the human leucocyte antigen (HLA) peptide-binding clefts strongly contributes to monoglandular and polyglandular autoimmunity (AP). Objective To investigate the impact of amino acid polymorphisms on the peptide-binding interactions within HLA class II and its association with AP. Design Immunogenetic study. Setting Tertiary referral center for autoimmune endocrine diseases. Subjects 587 subjects with AP, autoimmune thyroid disease (AITD), type 1 diabetes (T1D), and healthy unrelated controls were typed for HLA class II. Methods Amino acids within the peptide binding cleft that are encoded by HLA class II exon 2 were listed for all codon positions in all subjects. Overall comparisons between disease and control groups with respect to allele distribution at a given locus were performed by assembling rare alleles applying an exact Freeman Halton contingency table test with Monte-Carlo P values based on 150 000 samples. Results The Monte Carlo exact Fisher test demonstrated marked differences in all 3 loci, DQA1, DQB1, and DRB1 (P < .0001) between AP and both AITD and controls, as well as between AP type II (Addison’s disease as a major endocrine component) and AP type III (T1D + AITD). Differences were also noted between AP and T1D pertaining to the DRB1 allele (P < .041). Seven amino acid positions, DRB1-13, DRB1-26, DRB1-71, DRB1-74, DQA1-47, DQA1-56, and DQB1-57, significantly contributed to AP. Five positions in DQA1 (11, 47, 50, 56, and 69) completely correlated (P < .0001). Conclusion Amino acid polymorphisms within HLA class II exon 2 mediate the AP risk and differentiate between thyroid and polyglandular autoimmunity.


1992 ◽  
Vol 4 (9) ◽  
pp. 1055-1063 ◽  
Author(s):  
E. M. Riley ◽  
O. Olerup ◽  
S. Bennett ◽  
P. Rowe ◽  
S. J. Allen ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
pp. 1936757
Author(s):  
Pierre Dillard ◽  
Nicholas Casey ◽  
Sylvie Pollmann ◽  
Patrik Vernhoff ◽  
Gustav Gaudernack ◽  
...  

2020 ◽  
Vol 205 (1) ◽  
pp. 290-299
Author(s):  
Thomas Osterbye ◽  
Morten Nielsen ◽  
Nadine L. Dudek ◽  
Sri H. Ramarathinam ◽  
Anthony W. Purcell ◽  
...  

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