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.

Objective. To determine whether there is a link between the frequency of natural killer T (NKT) cells and high levels of IgG in patients with systemic lupus erythematosus (SLE) and their relatives.Methods. Blood samples were obtained from patients with SLE, their first-degree relatives, patients with rheumatoid arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined as CD56؉ T cells) was expressed as a percentage of total blood lymphocytes. Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA (dsDNA) were determined.Results. The frequency of NKT cells was lower in patients with SLE than in control subjects. No such decrease was observed in the relatives of patients with SLE or in patients with RA. High levels of IgG were observed in both patients with SLE and their relatives, while low levels of IgM were observed in these same groups. In relatives of patients with SLE, an inverse correlation between the frequency of NKT cells and IgG levels was observed. Moreover, raised levels of IgG in patients with SLE and their relatives and high levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT cells. Conclusion.These results suggest that NKT cells have an important role in the regulation of IgG production, although NKT cells with invariant T cell receptors may not necessarily be involved. NKT cells in the setting of SLE could lack the cytokine stimulus from NK or other cells that is needed to exert control on IgG production. Enhancement of NKT cell activity may provide a novel basis for therapy in SLE.

1. An analytical technique of isoelectric focusing in thin layers of polyacrylamide gel has been used to determine the isoelectric point, pI, of several proteins in the presence and in the absence of concentrated urea. 2. The presence of urea did not greatly affect pI except for bovine plasma albumin, where an increase of approx. 1pH unit was found. 3. Evidence is presented that this change in the pI of bovine plasma albumin is due to the normalization of certain ionizable groups on unfolding of the protein in urea. 4. Evidence is also presented that prolonged exposure of bovine plasma albumin to urea results in intramolecular disulphide interchange and that, on removal of urea, the new patterns of disulphide bonding stabilize abnormal conformations with pI values intermediate between those of the native and denatured states. 5. The studies demonstrate heterogeneity in bovine plasma albumin based on primary-sequence differences. 6. Isoelectric focusing of proteins in urea appears to be useful in the study of various aspects of protein structure.

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