Cold lymphocytotoxic antibodies in systemic lupus erythematosus

Optimum conditions were established for the assay of cold lymphocytotoxic antibodies (cLCTA) in serum from patients with systemic lupus erythematosus (SLE). The optimum temperature of the incubation step with complement was 15 degrees C. For target cells incubated with dextran a significantly higher percentage of damaged cells (p less than 0.005), a faster rate of cell damage (p less than 0.001) and a requirement for less complement was observed than for target cells not incubated with dextran. Under optimum conditions in the cytotoxicity assay, 62% of SLE sera damaged more than 60% of the target cells, whereas 73% of the sera from control donors damaged less than 20% of the target cells. In multiple serum samples obtained during follow-up of 30 patients with SLE, the serum cytotoxic activity or titer of cLCTA fluctuated and did not relate to clinical symptoms of disease activity. In sera obtained during active disease the cytotoxic activity was related to the anti-dsDNA antibody level and with levels of circulating immune complexes measured by the Raji cell assay and the indirect granulocyte phagocytosis test. We found no restricted reactivity of cLCTA against phenotypically distinct T-lymphocyte subpopulations with different immunoregulatory functions. The reactivity pattern of cLCTA towards the various T-lymphocyte subpopulations was not related to disease activity. We conclude that cLCTA in patients with SLE represent an epiphenomenon, being the result of a hyperreactive B-cell system rather than the cause of the disease.