A shared motif of hla-dpb1 affecting the susceptibility to pr3-anca positive granulomatosis with polyangiitis: comparative analysis of a Turkish cohort with matched healthy controls.
Rheumatol Int
; 41(9): 1667-1672, 2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-33544216
ABSTRACT
We aimed to analyse the distribution of HLA Class 2 genotypes which were reported among the genetic risk factors for ANCA-associated vasculitis (AAV) among Turkish patients in comparison with healthy subjects and previously reported data of AAV cohorts. Ninety-eight patients (F/M 47/51 and mean age 49 ± 1.14) were enrolled in the study and records of gender and birthplace-matched 196 healthy kidney donors were used as the control group. Patients were classified according to the clinical subgroups and ANCA serotypes (MPO-AAV, PR3-AAV). DNA was isolated from venous blood from all patients, and high-resolution HLA Class 2 genotyping was carried out by using NGS-Omixon Holotype HLA Kit. The frequencies of HLA-DQB1*0303, - *0604, and -DPB1*1301, -*1601 and -*660100 alleles were significantly higher, and the frequencies of HLA-DQB1*0202, -DPB1*0201 and -*0401 alleles were lower in the PR3-AAV subgroup (n = 53) compared to the controls. Comparison of amino acid sequences of the associated HLA-DPB1 alleles revealed the sequence of D-E-A-V in risk alleles replaced with the G-G-P-M sequence in protective alleles between 84 and 87th positions. Structural analysis of the HLA-DPB1*0201 showed that this shared position is in the contact area between HLA-DP α and ß chains and within pocket 1 of the antigen-binding groove. First HLA genotyping analysis in Turkish AAV patients revealed a negative correlation between PR3-ANCA positivity and certain HLA-DPB1 alleles contradictory to the results reported from European cohorts. Known functional effects of D-E-A-V sequence on HLA-DPB1 support the importance of our finding, but further studies are needed to reveal its pathogenic mechanisms.
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MEDLINE
Assunto principal:
Granulomatose com Poliangiite
/
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article