An Immunological Study Of Potential Pathogenic Mechanisms Associated With Arthritic Disease

The Gram-negative bacterium Klebsiella pneumoniae may. be an aetiological agent in the pathogenesis of any Losing spondylitis (AS). The association of disease activity in AS with ESR, CRP, total serum IgA and Hb levels was investigated and related to presence of bacterial antibodies. C-reactive protein (CRP) is an acute phase reactant found in serum, in association with inflammation. CRP levels were found to be significantly correlated with ESR and disease activity in AS patients. IgA is the major immunoglobulin of the external secretions in man. The mean level of ESR and CRP in AS patients with elevated serum IgA was significantly higher compared to levels in AS patients with normal IgA or in healthy controls. Elevated serum IgA levels also correlated with clinically defined disease activity. A mild anaemia is known to occur in chronic inflammatory diseases such as rheumatoid arthritis (RA). High Hb levels in AS patients were associated with low ESR, CRP and IgA levels as well as low levels of disease activity, when this was defined clinically. The specificity of serum IgA antibodies in the sera of AS patients and healthy controls was studied by absorption with various bacteria. Increased absorption of Klebsiella specific IgA antibodies was observed in AS patients with IgA levels greater than 300 mg/dl. Antibody titres to Klebsiella and Proteus were measured in AS and RA patients and healthy individuals by an indirect Coombs agglutination technique. Antibodies to Klebsiella were significantly elevated only in active AS patients whilst elevated anti-Proteus antibodies were found only in RA patients. Lymphocytes from AS patients and healthy controls were examined for morphological differences using scanning electron microscopy. Binding activity of rabbit anti Klebsiella serum for human lymphocytes was investigated using fluorescence microscopy. In an endeavour to reduce Klebsiella carriage a high protein, low carbohydrate diet was monitored in AS patients and healthy volunteers. Total serum IgA levels were significantly reduced in the control subjects. In the AS patients, a reduction in ESR, CRP and IgA levels was accompanied by a rise in Hb levels. The results presented in this thesis support the cross-tolerance hypothesis and show that this could provide a possible pathogenetic mechanism in arthritic diseases such as AS and RA. Infection with bacteria bearing antigens stereo chemically similar to self antigens can evoke the formation of autoantibodies. Evidence of elevated specific anti Klebsiella and anti-Proteus antibodies in "active" AS and RA patients is presented in this thesis.