Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal sites

Elevated serum levels of IgA, IgA1, and IgA2 rheumatoid factors (RF) were demonstrated by enzyme-linked immunosorbent assay in 69%, 73%, and 36%, respectively, of 100 patients with rheumatoid arthritis (RA), whereas fewer than 5% of 100 healthy donor sera contained elevated levels of these RFs. In serum samples from 125 controls with 4 different chronic diseases (systemic lupus erythematosus, ankylosing spondylitis, bronchial asthma, and polyarteritis nodosa), levels of IgA-, IgA1-, and IgA2-RF were found to be increased in 7%, 7%, and 8%, respectively. Comparison of RF levels in samples of serum, synovial fluid (SF), and saliva from RA patients indicated local production of both IgA-RF subclasses in salivary glands and in synovial tissue. Significant positive correlations were found between levels of IgA-RF subclasses in SF and serum, but not in serum and saliva or in SF and saliva. Fractionation of serum, SF, and saliva from patients with RA (by high performance liquid chromatography under acidic conditions) demonstrated that both IgA subclasses with RF activity occur mainly in fractions that also contain IgM. The results of this study show that 1) IgA-RF in serum and SF is mainly of IgA1 subclass, 2) both IgA-RF subclasses are produced locally in salivary glands and in synovial tissue, 3) the production of both IgA-RF subclasses at mucosal and nonmucosal sites is independent from each other, and 4) both IgA-RF subclasses occur predominantly in polymeric form in serum, SF, and saliva in RA patients.