Anti-staphylococcal responses and their relationship with HLA-DR-DQ polymorphism in granulomatosis with polyangiitis: a preliminary evidence of association with disease outcome

Clin Exp Med. 2022 Jul 26. doi: 10.1007/s10238-022-00865-6. Online ahead of print.

Abstract

Chronic nasal carriage of Staphylococcus aureus (S. aureus) is a risk factor for relapse of granulomatosis with polyangiitis (GPA), and genetic susceptibility to infections and autoimmune diseases is majorly affected by HLA genes. Previous studies have shown the association of HLA Class-II genes with GPA susceptibility. Here, we aim to assess immune responses of GPA patients against S. aureus antigens in relation to the HLA-DR-DQ genes polymorphism to determine the disease outcome. A total of 45 GPA patients and 128 healthy controls during 2010-2012 were included in this case-control study. HLA-DRB1/DQB1 allele typing was performed by polymerase chain reaction-sequence-specific primer (PCR-SSP) method. Immune responses against S. aureus antigens were investigated in 20 active vs. remitting GPA (after 6 months of cyclophosphamide and glucocorticoids) patients by Western blot. Statistical analysis was performed using χ2 test and Fisher's exact test. We observed a significant association of DRB1*08, DRB1*16 and DQB1*04 alleles with GPA susceptibility, whereas DRB1*15, DRB1*10 and DQB1*05 alleles were suggested as protective alleles. Among S. aureus antigens, active GPA patients' sera reacted more strongly with 34 and 24 kDa antigens of S. aureus than remitting and healthy control sera. Furthermore, we observed that the lack of DQB1*06 allele confers complete remission even in the presence of anti-S. aureus antibodies against 24 kDa protein. Our findings suggest that the presence of DQB1*06 allele and S. aureus infection may prolong active disease. Further, our study indicates the potential of using anti-staphylococcal medications for achieving remission in patients having HLA-DQB1*06 allele.

Keywords: Clinical outcome; GPA; HLA; Immune response; S. aureus.