The antigenic trigger for two major inflammatory diseases—rheumatoid arthritis (RA) and ankylosing spondylitis (AS)—has again eluded identification after two more potential culprits failed to elicit an increased immune response in patients.

A small study has shown that human heat shock protein 60 (h-HSP60) and yersinia 19 kDa urease β subunit do not provoke a significantly enhanced immune response in T cells from peripheral blood or synovial fluid from patients with RA and AS when compared with T cells from controls in stimulation tests in vitro.

The tests were conducted on 22 patients with active RA and 45 patients with active AS recruited from an outpatient clinic and 20 healthy controls. CD4+ T cells from peripheral blood and synovial fluid—from a subset—were tested for stimulation by each protein antigen for six hours—the last four with brefeldin A to ensure accumulation of intracellular cytokines—then fixed and stained for CD4+, CD69 cell surface marker, interferon γ (IFNγ) or tumour necrosis factor α (TNFα). After gating on CD4+ cells, those cells stained double positive for CD69—indicating early activation by antigen—and INFγ or TNFα were scored.

Both potential protein antigens have been linked to inflammatory rheumatic diseases. h-HSP60 has long been suspected, and the 19 kDa urease β subunit of yersinia is the major antigen for T cells and specific antibody stimulant in yersinia reactive arthritis. A notable proportion of HLA-B27 positive patients with this condition develop AK long term.