What is the role of HLA B27 in Reactive Arthritis pathogenesis?
There are several hypotheses to date: 1) Misfolding hypothesis: HLA-B27 folds more slowly than other HLA types when assembled in the endoplasmic reticulum. This may cause inadequate folding and instability of HLA-B27 leading to accumulation of such molecules with activation of inflammatory processes. 2) Arthritogenic peptide hypothesis: postulates that HLA-B27 on antigen-presenting cells present microbial peptides that may mimic certain self-peptides (molecular mimicry) to CD8 cytotoxic T lymphocytes, leading to autoimmunity. Alternatively, the similarity between the microbial and self-peptides may allow microbial fragments to persist due to an inadequate immune response. 3) Heavy chain homodimer hypothesis: HLA-B27 can be expressed on the cell surface as a homodimer of heavy chains without ß-2 microglobulin. These abnormal chains can activate natural killer, T, and B cells.