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

Abstract

SummaryNatural 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.

Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG production

“…We previously reported a tendency toward low blood levels of natural killer (NK) cells in relatives of patients with the autoimmune disease systemic lupus erythematosus (SLE) (1). In that study, NK cells were defined as lymphocytes expressing surface CD56 but not CD3.…”

“…Details regarding the ages and ethnic backgrounds of the participants, as well as drug therapy for and the clinical disease activity of the patients, have been described previously (1). Disease activity in SLE was assessed using the system described by the British Isles Lupus Assessment Group (8), in which disease activity in each of 8 organs/systems (e.g., mucocutaneous, neurologic, renal) is assigned a category from A (most active) to D (currently inactive) or E (no current or previous involvement).…”

“…NKT cells are defined as CD56ϩ,CD3ϩ cells, and their frequency is expressed as a percentage of total lymphocytes (T cells including NKT cells, B cells, and NK cells). Occasionally, the percentage of NKT cells is converted to absolute numbers of circulating NKT cells by referring to the blood lymphocyte count (1).…”

“…Flow cytometric analysis of blood mononuclear cells was performed as described previously (1). NKT cells are defined as CD56ϩ,CD3ϩ cells, and their frequency is expressed as a percentage of total lymphocytes (T cells including NKT cells, B cells, and NK cells).…”

“…We also examined the relationships between the levels of total IgG, total IgM, or IgG anti-dsDNA antibodies and NK cell frequency or lytic activity (1). No results paralleled the relationships seen with NKT cells, apart from a significant inverse correlation between the level of IgM and the percentage of NK cells in female relatives of patients with SLE (r ϭ -0.48, P Ͻ 0.01).…”