Impaired natural killing activity in patients with rheumatoid arthritis. Clinical characteristics and a study of defective mechanisms.

: We have studied NK activity against K562 cells of peripheral blood mononuclear cells (PBMC) from 83 patients affected with RA and searched for correlations with some clinical and laboratory parameters. In 65 patients T lymphocyte subsets were investigated by laser flow cytometry using monoclonal antibodies against OKT3, OKT4 and OKT8 antigens and in 25 patients also HNK-1+ cells were enumerated. NK activity in patients with RA resulted significantly decreased compared with controls (relative cytotoxic index = 0.68 +/- 0.74 versus 1.00 +/- 0.60, p less than 0.01). Decreased NK activity was not correlated with sex, age, duration of disease, ESR, haemoglobin, serum alpha-2-globulin, serum gamma-globulin, rheumatoid factor titre. The only clinical parameter correlated with decreased NK activity was the anatomical stage of the disease. NK activity depression resulted to be significantly correlated with OKT3+ cell percentage and at a lesser extent with OKT4+ and OKT8+ cell percentages. HNK-1+ cell percentage resulted only slightly reduced in patients with RA (13.1 +/- 8.7 versus 15.0 +/- 7.0) and there was only a modest correlation (p approximately equal to 0.10) between NK activity and HNK-1+ cell percentage. In order to elucidate the mechanisms of impaired NK activity in RA, experiments in vitro were carried out on PBMC of 23 patients to investigate the effects of the depletion of cells adherent to plastic, incubation with beta-interferon (1000 IU/ml) and incubation with indomethacin (10 -6M). Our data suggest that decreased NK activity in RA is mainly due to functional immaturity of NK cells and sometimes to inhibition by monocytes in some cases probably through prostaglandin release.