Random one way microtiter mixed lymphocyte cultures between 43 rheumatoid arthritis (RA) patients and 45 controls comprising 26 normal subjects and 19 miscellaneous non RA patients were performed and results were evaluated as relative responses. Low responses (consisting of relative responses <38%) were found in 31 out of 43 RA patients in cultures against 8 of the RA stimulators. The remaining 35 RA stimulators tested yielded only normal mixed lymphocyte culture reactions. The same RA patients used as responders never produced low responses when stimulated by non RA lymphocytes. But 6 of the control subjects gave low responses to 2 RA stimulators. The low responses did not appear to correlate with intake of aspirin, prednisolone, or gold salts, nor could they be reproduced by addition of RA serum or 7S or 19S fractions thereof containing either polyclonal or monoclonal rheumatoid factors. Short term culture and washing before mixing with the allogeneic cells did not change the low responses suggesting that in vivo bound autoantibodies against lymphocyte receptors were not involved. Study of the inheritance of HLA and mixed lymphocyte culture determinants in the family of one patient who most frequently elicited low responses indicated that she was homozygous for a lymphocyte defined determinant which has been called R. Her low responses could be interpreted as typing responses based on sharing of the same or of a similar lymphocyte defined determinant. This gene appears to be increased in patients with RA with respect to non RA controls and may reflect an association of genes within the HLA chromosomal region leading to a predisposition for the development of RA.
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