Natural killing activity in Sjögren's syndrome. An analysis of defective mechanisms.

Natural killing (NK) by peripheral blood mononuclear cells (PBMC) against K562 cells was examined in 27 patients with Sjögren's syndrome and 17 normal controls. NK activity in the patients was significantly reduced compared with normal controls (34.6 +/- 3.4% versus 52.2 +/- 3.4%, P less than 0.001). Patients with secondary Sjögren's had lower cytotoxicity compared with those who had primary Sjögren's (28.5 +/- 5.5% versus 37.3 +/- 4.2%, P less than 0.01). The proportion of PBMC with characteristics of NK cells was not decreased in the patients. NK by normal PBMC was diminished both in the presence of sera from patients with reduced NK and when the effector cells were pretreated with the sera. Pretreatment of target K562 cells did not alter NK activity. Suppression of NK by sera from patients did not correlate with levels of immune complexes or with antilymphocyte antibodies. Some patients had adherent cells which inhibited NK function. Addition of either indomethacin or catalase partially restored NK activity in such patients, indicating that both prostaglandins and hydrogen peroxide play a role in suppression. These data suggest that multiple mechanisms are involved in the defective NK activity seen in patients with Sjögren's syndrome. The reduction of NK activity in Sjögren's syndrome may contribute to the increased incidence of lymphoid malignancy.