Serum IL-12 in systemic lupus erythematosus: absence of p70 heterodimers but presence of p40 monomers correlating with disease activity.

Biologically active IL-12 is a 70 kDa heterodimeric cytokine (IL-12 p70) mainly produced by antigen-presenting cells (APC) and made of disulfide-linked alpha (p35) and beta (p40) chains. Since the production of the p40 subunit is independently regulated from that of IL-12 p70, we compared levels of p40 and IL-12 p70 in the sera of patients with systemic lupus erythematosus (SLE). Sera obtained from rheumatoid arthritis (RA) patients and healthy subjects were used as controls. Serum p40 titers were significantly higher in SLE patients (mean +/- s.e.m.: 348 +/- 40 pg/ml) compared with patients with rheumatoid arthiritis (mean +/- s.e.m.: 116 +/- 18 pg/ml, P < 0.0001) or controls (mean +/- s.e.m.: 0 +/- pg/ml, P < 0.0001). By contrast, IL-12 p70 was not detected in any serum. In SLE patients, serum p40 levels were positively correlated with the SLEDAI (r = + 0.56, P = 0.02) and negatively with serum C3 levels (r = - 0.42, P = 0.03). Follow-up measurements indicated that serum p40 dropped significantly after immunosuppressive therapy. Finally, size exclusion chromatography with p40 immunoprecipitates obtained from SLE sera demonstrated that p40 was present as a monomer, and not as a homodimer, nor as a p19/p40 (IL-23) heterodimer. In conclusion, serum p40 monomers (but not IL-12 p70 titers) are elevated in the sera of SLE patients commensurate with disease activity. While the relevance of these observations needs to be further investigated, our results are consistent with the APC dysfunction described in SLE.