Molecular heterogeneity of prolactin in the plasma of patients with systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) has been associated with high levels of prolactin in the circulation of some patients. Although prolactin stimulates immune responses, the relationship between hyperprolactinemia and the pathophysiology of SLE remains controversial. This study was undertaken to investigate whether circulating bioactive prolactin isoforms are associated with the activity of SLE. The molecular heterogeneity of prolactin was studied in the plasma of patients with active and inactive SLE and in healthy volunteers by radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), Nb2-cell bioassay, and immunoprecipitation-Western blots. The specificity of the bioassay determinations was assessed by neutralization of growth-promoting effects with antiserum to human prolactin. Significantly higher prolactin levels were detected by bioassay and by ELISA than by RIA in both subsets of SLE patients and in normal individuals. Plasma prolactin levels in the SLE patients were significantly greater than those in the normal controls when measured by ELISA, but not by RIA or bioassay. The bioassay:ELISA and bioassay:RIA ratios were similar between SLE patients and controls, suggesting that prolactin biopotency was not altered with the disease, and none of the 3 assays detected a difference in prolactin levels between patients with active SLE and those with inactive SLE. However, the prolactin detected in plasma was associated with immunoreactive proteins of 130 kd and 23 kd, and the concentration of the 130-kd prolactin-like species was 10-fold higher in inactive SLE versus active SLE patients. Discrepancies among assays substantiate the molecular heterogeneity of circulating prolactin. The prolactin isotype that is found in association with inactive SLE could be of potential use as a marker for the inactive form of the disease and as an index for the efficacy of treatment.