An analysis by ELISA of 100 rheumatoid factor (RF)-positive sera selected at random from a collection of sera from patients with various auto-immune diseases and joint pains, and 100 RF-negative sera from the same collection matched by patient age and gender, showed that the RF-positive sera had highly significantly (p ≪ 0·0001) raised levels of IgM antibody, but not IgG antibody, to over those of the RF-negative sera. This response was subsequently found to be associated with sera from patients who clinically had rheumatoid arthritis (RA). Sera from the RA patients had significantly greater amounts (p = 0·026) of IgM antibody to than to the other organisms tested and these values were also highly significantly different (p ≪ 0·0001) from IgM antibody levels in matched RF-negative sera. Sera from RA patients also had significantly greater amounts of IgA to (p ≪ 0·0001) and greater amounts of IgM to (p ≪ 0·0001) and (p ≪ 0·0001) than those in matched RF-negative sera. Other classes of antibody to these organisms and all classes of antibody to were not raised in the sera of RA patients over those of RF-negative controls. The IgM response in RA patients was not specific for only one O serotype of but was associated with all 11 different O serotypes of tested and those of other spp. Moreover, the IgM antibodies to spp. appeared to be independent from C-reactive protein and RF. Fourteen of 27 sera from RA patients had an IgM antibody that reacted with an internal 90-kDa protein of . This antibody was not found in RF-positive sera of patients with Sjogren's disease or systemic lupus erythematosus, nor in other RF-negative sera, nor in those of healthy people, nor in those with osteoarthritis or ankylosing spondylitis. IgM antibodies capable of reacting with the haemolysin protein Hpm B of were not found in sera of RA patients of unknown HLA status.


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