Abstract
Spondyloarthritis (SpA) comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA)-B27. A triggering bacterial infection has been considered as the cause of SpA, and bacterial heat shock protein (HSP) seems to be a strong T cell antigen. Since bacterial and human HSP60, also named HSPD1, are highly homologous, cross-reactivity has been suggested in disease initiation. In this study, levels of antibodies against bacterial and human HSP60 were analysed in SpA patients and healthy controls, and the association between such antibodies and disease severity in relation to HLA-B27 was evaluated.Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from Chlamydia trachomatis, Salmonella enteritidis and Campylobacter jejuni. Disease severity was assessed by the clinical scorings Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI).Levels of IgG1 and IgG3 antibodies against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27+ patients. Only weak correlation between antibodies against bacterial and human HSP60 was seen, and there was no indication of cross-reaction.These results suggest that antibodies against human HSP60 is associated with SpA, however, the theory that antibodies against human HSP60 is a specific part of the aetiology, through cross-reaction to bacterial HSP60, cannot be supported by results from this study. We suggest that the association between elevated levels of antibodies against human HSP60 and disease may reflect a general activation of the immune system and an increased expression of human HSP60 in the synovium of patients with SpA.
Highlights
Spondyloarthritis (SpA) comprises a heterogeneous group of chronic inflammatory diseases, including reactive arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease (IBD) associated arthritis and undifferentiated spondyloarthritis
Correlation between antibodies against HSP60 from different bacteria was demonstrated, but no evidence of cross-reaction to human HSP60 was found, since only limited correlation occurred between antibodies to human and bacterial HSP60
The predominant IgG subclasses produced in response to human and bacterial HSP60 were different, IgG3 and IgG1, respectively
Summary
Spondyloarthritis (SpA) comprises a heterogeneous group of chronic inflammatory diseases, including reactive arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease (IBD) associated arthritis and undifferentiated spondyloarthritis. Assessments of disease activity, the physical function and the spinal mobility of ankylosing spondylitis patients are performed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI), respectively. These indexes are based on clinical measurements (BASMI) along with questions pertaining degree of functional limitation and symptoms (BASDAI and BASFI) [2]. An interaction between HLA-B27 and a triggering bacterium as part of disease initiation has been suggested, partly based on animal studies [1,3]. Evidence supporting a preceding bacterial infection in other spondyloarthritides is limited [1], and the potential interplay between HLA-B27 and bacteria in the development of SpA in humans remains to be proven
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