Background Idiopathic inflammatory myopathies (IIM) belong to the group of systemic autoimmune diseases. IIM are characterized clinically by chronic muscle inflammation leading to a dysfunction and/or destruction of muscle cells. Like many other autoimmune diseases, IIM have its major genetic predisposition linked to the MHC genes.
In this study, we have analyzed MHC haplotypes involving alleles of HLA class II genes (DQB1, DRB1) and 6 polymorphisms located within the HSP70 genes (HSPA1A, HSPA1B and HSPA1L). Frequencies of all polymorphisms and haplotypes were studied in a cohort of patients with IIM and compared with healthy controls.
Objectives The aim of this study was to investigate the relation between MHC haplotypes and the risk of IIM development in a single center cohort.
Methods We have analyzed 82 patients with dermatomyositis (DM) and 70 patients with polymyositis (PM) diagnosed according to Bohan and Peter criteria and compared them with 150 healthy controls. In total, six genetic polymorphisms located within the three HSP70 genes were analyzed by direct genomic DNA sequencing. Additionally, HLA-DRB1 and HLA-DQB1 loci were genotyped using the commercial LABType® SSO kit (One Lambda, USA). The statistical analysis was done using Fisher's exact test with calculated p<0.05 considered as statistically significant.
Results The most frequent MHC haplotype in controls, total IIM, as well as in DM and PM subgroups was found to be the HLA-DQB1*02-DRB1*03:01-T-C-C-G-C-INS haplotype. However, the difference in frequency between patients and controls reached statistical significance only for IIM overall (p<0.01; OR=1.90, CI (95%): 1.15, 3.13) and the DM subgroup (p<0.05; OR=1.82, CI (95%): 1.02, 3.23). There was not a statistically significant difference between the PM subgroup and controls.
The HLA-DQB1*05–DRB1*16:01-T-A-G-A-G-DEL haplotype was found to have the strongest disease association in all patient subgroups. The difference was the highest in the IIM overall (p<0.0001; OR=32.18, CI (95%): 1.92, 540.60) and remained significant when the DM subgroup (p<0.01; OR=32.64, CI (95%): 1.87, 569.60) as well as the PM subgroup (p<0.001; OR=29.04, CI (95%): 1.62, 519.70) were analyzed separately.
When comparing the MHC background of DM and PM, we have found another haplotype (HLA-DQB1*03-DRB1*11:01-T-A-G-A-G-DEL) differentially associated with these diagnoses. The difference in frequency of this haplotype between DM and PM reached statistical significance with p<0.01.
Conclusions Our results show a strong association between distinct MHC haplotypes and IIM in general. Additionally, we have identified one MHC haplotype suggesting, that DM and PM may have partially different genetic background. HSP70 polymorphisms are located nearby the HLA-DRB1 gene. Therefore, combination of distinct HLA-DRB1 alleles and HSP70 polymorphisms can help in identification of higher genetic risk for development of myositis.
Acknowledgements This study was supported by the Internal Grant Agency of the Ministry of Health in the Czech Republic [MZČR NT 13699], and Institutional support of MHCR VZ (00023728).
Disclosure of Interest None declared