Polymorphisms of HSP70 genes are involved in the pathogenesis of idiopathic inflammatory myopathy

Idiopathic inflammatory myopathies (IIM) are a group of rare systemic autoimmune diseases characterized by muscle weakness, histopathological signs of inflammation in muscle tissues, elevated serum levels of muscle-associated enzymes, inflammatory mononuclear cells infiltrating muscle tissue and progressive symmetrical proximal muscle weakness. The current view is that they begin by immune activation in response to environmental factors in genetically predisposed people, but despite the number of investigations into the genetic background, the detailed etiopathogenesis remains unknown. The aim of this study was to examine the relationship between select polymorphisms located in the human major histocompatibility complex (MHC) and IIM. These genetic markers may take part in the onset of the autoimmune process, and their identification could aid in the diagnosis and classification of IIM subtypes.

One hundred and fifty-two adult patients suffering from IIM (82 dermatomyositis and 70 polymyositis) and 150 healthy controls were analyzed in this study. All were from the Czech Republic. SNPs of the HSP70 genes HSPA1A (rs1008438, rs1043618), HSPA1B (rs1061581, rs539689, pentanucleotide tandem duplication rs9281590) and HSPA1L (rs2227956) were analyzed in all patients and controls. For the detection of HLA polymorphisms, we used commercial kits from CareDx. Haplotypes were created using Arlequin 3.5.

Our results confirm the association of IIM with the ancestral haplotype HLA-DRB1*03-DQB1*02. The most important MHC haplotype related to IIM and covering all polymorphisms was HLA-DQB1*02-DRB1*03:01-T-C-C-G-C-INS (p < 0.05, OR = 1.90, 95% CI: 1.15-3.13). This haplotype is associated with the risk of IIM development.

Our results show that polymorphism typing within the MHC might be a very strong tool for recognition of IIM.