Natural killer cell activity in families of patients with systemic lupus erythematosus: demonstration of a killing defect in patients

Abstract

Natural killer (NK) cell cytotoxic activity and cell frequency, expressed as a percentage of total lymphocytes, have been determined in peripheral blood mononuclear cells from first-degree relatives of patients with systemic lupus erythematosus (SLE), the patients themselves, a group of rheumatoid arthritis (RA) patients and controls. Low levels of killing activity relative to controls were found in some members of all groups with the extent of depression falling into two ranges. Moderate reductions were seen in female (3/31, 10%) and male (4/14, 29%) relatives of SLE patients, female (12/60, 20%) and male (3/4, 75%) SLE patients and female RA patients (6/17, 35%). A more profound depression of killing activity was confined to other female SLE patients (15/60, 25%). There were strong correlations in all groups between killing activity and percentage of NK cells, but analysis of the ratio of these parameters and studies with purified preparations of NK cells suggest that the reduced activity in SLE frequently involves a defect in the killing capacity of the individual cells in addition to the reduced levels of NK cells. Azathioprine (AZA), which was used in treatment of 12 SLE patients, was invariably associated with low values of killing activity. It appears to substantially reduce the percentage of NK and B cells in an action unconnected with the NK cell abnormalities associated with SLE. The finding of low killing activity in relatives and a correlation between their activity and that of their patients support the view that NK cell deficiency is a genetic determinant of SLE. NK cells in SLE may produce insufficient levels of cytokines required for the regulation of IgG production.

Fig. 1

Natural killing activity in SLE patients, their first-degree relatives, rheumatoid arthritis patients and controls. Activity is expressed relative to the prime control donor. Assays were set up at a PBMC to target cell ratio of 20. Points on the baseline represent values less than 0·01.

Fig. 4

Ratios of natural killing activity to percentage NK cells in relative, patient and control groups.

Fig. 2

NK cell levels expressed as a percentage of total lymphocytes (% NK cells) in relative, patient and control groups. Points on the baseline represent values of less than 1%.

Fig. 3

Relationship between natural killing activity in SLE patients and in their respective first-degree relatives. Both male and female relatives are included and all but one of the patients were female. Where there was data from more than one relative of the same patient mean values have been used. The best-fit line (linear regression) is shown.

Fig. 5

Relationship between natural killing activity in SLE patients and their global disease activity scores. All SLE patients are included – those not receiving azathioprine (○); those on azathioprine (•).