Selective dysregulation of the FcgammaIIB receptor on memory B cells in SLE
Mackay, Meggan; Stanevsky, Anfisa; Wang, Tao; Aranow, Cynthia; Li, Margaret; Koenig, Scott; Ravetch, Jeffrey V; Diamond, Betty
The inappropriate expansion and activation of autoreactive memory B cells and plasmablasts contributes to loss of self-tolerance in systemic lupus erythematosus (SLE). Defects in the inhibitory Fc receptor, FcgammaRIIB, have been shown to contribute to B cell activation and autoimmunity in several mouse models of SLE. In this paper, we demonstrate that expression of FcgammaRIIB is routinely up-regulated on memory B cells in the peripheral blood of healthy controls, whereas up-regulation of FcgammaRIIB is considerably decreased in memory B cells of SLE patients. This directly correlates with decreased FcgammaRIIB-mediated suppression of B cell receptor-induced calcium (Ca2+) response in those B cells. We also found substantial overrepresentation of African-American patients among those who failed to up-regulate FcgammaRIIB. These results suggest that the inhibitory receptor, FcgammaRIIB, may be impaired at a critical checkpoint in SLE in the regulation of memory B cells; thus, FcgammaRIIB represents a novel target for therapeutic interventions in this disease.
Prolactinoma and systemic lupus erythematosus: do serum prolactin levels matter? [Case Report]
Li, Margaret; Keiser, Harold D; Peeva, Elena
The lactogenic hormone prolactin is produced in part by cells of the immune system and serves as an upregulator of immune function. Hyperprolactinemia is common in patients with systemic lupus erythematosus (SLE), raising the possibility that the hormone contributes to the excessive immune response in the disease. The highest levels of circulating prolactin occur in association with prolactin-secreting tumors, but prolactinomas have only rarely been encountered in patients with SLE. We present here three patients with SLE and prolactinomas. As with the previously reported six patients, there was no consistency in the presence of findings related to prolactin excess or in the coincidence of hyperprolactinemia with flares of SLE disease activity. We speculate that this may be due to genetic differences in the response to prolactin and/or to the presence of variant prolactin isoforms detected in the clinical immunoassay that have reduced or absent biologic activity.