Biologic activity and plasma clearance of prolactin–IgG complex in patients with systemic lupus erythematosus

Abstract

Objective. To characterize the clinical findings in hyperprolactinemic systemic lupus erythematosus (SLE) patients with or without macroprolactinemia (big, big prolactin [PRL]) due to anti-PRL autoantibodies (PRL-IgG complex), and to assess the bioactivity and structure of big, big PRL.Methods. Twenty-seven SLE patients with hyperprolactinemia (HPRL) were studied. Patients with (n ‫؍‬ 8) or without (n ‫؍‬ 19) big, big PRL were identified by gel filtration chromatography and affinity chromatography for IgG. PRL concentrations in serum and fractions by gel filtration chromatography and affinity chromatography were characterized by immunoradiometric assay (IRMA), Nb2 bioassay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, and clearance studies.Results. SLE patients without big, big PRL had significantly higher levels of disease activity, causeproven HPRL, and menstrual disturbances compared with patients with big, big PRL (P < 0.05). The big, big PRL fractions by Western blotting revealed a single 23-kd nonglycosylated PRL. The Nb2:IRMA ratio of the samples with big, big PRL was significantly higher than that of the samples without big, big PRL (P < 0.02). However, bioactivity of big, big PRL in the Nb2 cells was very similar to that of 23-kd nonglycosylated PRL.Clearance studies in rats demonstrated that the PRL-IgG complex was eliminated more slowly than monomeric PRL (little PRL).Conclusion. We demonstrated that the PRL-IgG complex was formed by 23-kd nonglycosylated PRL that was noncovalently bound to IgG and showed that the complex was fully active in vitro. This result suggests that the absence of symptoms of HPRL or lower levels of lupus activity in these patients is not explained by lower bioactivity of the complex. Instead, because of the large molecular size of the complex, the PRL does not easily cross the capillary walls. Delayed clearance of the PRL-IgG complex may account for increased serum levels of PRL in SLE patients with anti-PRL autoantibodies.

Prolactin and Autoimmunity

“…A subset (30-40%) of SLE patients with HPRL has detectable anti-PRL antibodies with fewer clinical and serological manifestations due to the fact that anti-PRL antibodies attenuate the biological activity of PRL [16]. However, in vitro studies demonstrated that macroprolactin from SLE patients is fully active [22].…”

Spotlight on the role of hormonal factors in the emergence of autoreactive B-lymphocytes

“…Glycosylation lowers its receptor binding and immunologic reactivity [43]. Because of its large size, immunoglobulin-bound prolactin is not significantly bioactive [44].…”

“…In addition, some SLE patients have antibodies against prolactin [128] that could deregulate prolactin secretion and induce hyperprolactinemia. Since the prolactin present in immune complexes formed with anti-prolactin antibodies does not seem to be biologically active, SLE patients with these complexes may have less prolactin-induced effects on lupus disease activity than patients with similar serum prolactin levels, but without immune complexes [44]. Genetic factors may also be implicated in the discrepancies between the degree of hyperprolactinemia and SLE disease activity, and it is possible that only a subset of SLE patients have a prolactin-responsive disease.…”

Anti-prolactin autoantibodies in pregnant women with systemic lupus erythematosus: maternal and fetal outcome

“…25 Interestingly, patients with anti-PRL autoantibodies had less clinical and serological SLE activity than those without anti-PRL autoantibodies (with only the presence of monomeric or little PRL in their blood). 25,26 In addition, we recently described the course of the pregnancy in a woman with SLE and macroprolactinemia due to anti-PRL autoantibody. Interestingly, despite her high serum levels of PRL, no clinical lupus activity was present during follow-up, and her pregnancy was uneventful.…”