Current theory for the pathogenesis of a postenteritic reactive arthritis
- Bacterial lipopolysaccharide antigens (but not viable organisms or nucleotides) from the pathogens ( Yersinia, Shigella, Salmonella ) causing the infectious gastroenteritis have been shown to be deposited in the joints of patients who develop a postenteritic reactive arthritis.
- These bacterial cell wall components are thought to incite inflammation in the joint.
- The role that HLA-B27 plays in the pathogenesis is debated.
- One possibility is that recirculating HLA-B27 –restricted T cells present bacteria-derived peptides with arthritogenic properties to the immune system in a unique way, leading to inflammation.
- Another postulate is that there is molecular mimicry between the HLA-B27 molecule and the bacterial antigens, causing an aberrant immune response leading to altered or defective intracellular killing by HLA-B27 –positive cells, resulting in persistence of arthritogenic pathogens.
- A third hypothesis relates to the tendency for the HLA-B27 heavy chain to misfold when the cell is under stress.
- This results in heavy chains accumulating in the endoplasmic reticulum leading to an “unfolded protein response,” causing the release of inflammatory cytokines.
- The chronic persistence of bacterial antigens may stress the HLA-B27 –positive cells, leading to B27 heavy chain misfolding and the unfolded protein response.
- However, because HLA-B27 positivity is neither necessary nor sufficient to cause reactive arthritis, additional genetic (endoplasmic reticulum aminopeptidase–1 and interleukin 23R polymorphisms) and environmental factors likely play a role in the pathogenesis of postenteritic reactive arthritis.
