The Combination of Apoptotic U937 Cells and Lupus IgG Is a Potent IFN-α Inducer

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Abstract
Patients with active systemic lupus erythematosus (SLE) have signs of an ongoing IFN-α production, that may be of pathogenic significance in the disease. We previously showed that SLE patients have an IFN-α-inducing factor in blood, probably consisting of complexes containing anti-DNA Abs and immunostimulatory DNA. The DNA component could be derived from apoptotic cells, because SLE patients have been reported to have both increased apoptosis and reduced clearance of apoptotic cell material. In the present study, we therefore investigated whether apoptotic cells, together with IgG from SLE patients, could act as an IFN-α inducer in normal PBMC in vitro. We found that apoptotic cells of the myeloid leukemia cell line U937 as well as four other cell lines (MonoMac6, H9, Jurkat, U266) could induce IFN-α production in PBMC when combined with IgG from SLE patients. The IFN-α production by PBMC was much enhanced when PBMC were costimulated by IFN-α2b. The ability of IgG from different SLE patients to promote IFN-α induction by apoptotic U937 cells was associated with the presence of anti-ribonucleoprotein Abs, but not clearly with occurrence of anti-DNA Abs. These results suggest that apoptotic cells in the presence of autoantibodies can cause production of a clearly immunostimulatory cytokine, which is IFN-α. This mechanism for induction of IFN-α production could well be operative also in vivo, explain the IFN-α production seen in SLE patients, and be important in the pathogenesis of SLE.

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