Abstract: Elevated Serum Bioactive Prolactin Concentrations in Patients with Systemic Lupus Erythematosus Are Associated with Disease Activity as Disclosed by Homologous Receptor Bioassays

Elevated Serum Bioactive Prolactin Concentrations in Patients with Systemic Lupus Erythematosus Are Associated with Disease Activity as Disclosed by Homologous Receptor Bioassays

GUADALUPE CÁRDENAS-MONDRAGÓN, ALFREDO ULLOA-AGUIRRE, IRMA ISORDIA-SALAS, VINCENT GOFFIN, and ALFREDO LEAÑOS-MIRANDA

ABSTRACT.

Objective. To assess the bioactivity of circulating prolactin (PRL) in serum samples from patients with systemic lupus erythematosus (SLE) using 2 novel homologous in vitro bioassays, and to correlate PRL bioactivity with lupus activity.

Methods. Serum samples from 98 SLE patients with and without disease activity were tested for immunoreactive and bioactive concentrations of PRL.

Results. Patients with active disease exhibited higher bioactive serum PRL levels in homologous bioassays (p ≤ 0.013). In contrast, bioactivity in Nb2 cells was similar between patients with and without activity. The bioactive/immunoreactive PRL ratio (BA/IA) in homologous bioassays was significantly higher in patients with both clinical manifestations and serological indicators of lupus disease activity. SLE patients with idiopathic hyperprolactinemia (HPRL) and macroprolactinemia (MPRL) had low SLEDAI scores, and the BA/IA ratio in homologous bioassays was significantly lower compared to those with idiopathic HPRL and no MPRL. There was a negative but significant correlation between MPRL and BA/IA in homologous bioassays (p < 0.001), but not when the heterologous bioassay was employed.

Conclusion. Elevated serum bioactive PRL levels revealed by homologous bioassays were associated with disease activity, as well as with specific organ involvement. Big big PRL or macroprolactin is a PRL variant with reduced bioactivity towards its homologous receptor, and this altered bioactivity may contribute to the lower disease activity and absence of symptoms related to HPRL in SLE patients. These novel data must be considered in future studies to establish a relationship between PRL and disease activity in SLE. (First Release May 15 2007; J Rheumatol 2007;34:1514-21)

Key Indexing Terms:

PROLACTIN
MACROPROLACTIN
PROLACTIN BIOASSAYS
SYSTEMIC LUPUS ERYTHEMATOSUS
DISEASE ACTIVITY

From the Research Unit in Reproductive Medicine, Hospital de Ginecología y Obstetricia "Luis Castelazo Ayala," Instituto Mexicano del Seguro Social (IMSS), México DF, Mexico; and Université Paris-Descartes, Faculté de Médecine, Hopital Necker, and Inserm, U808, Paris, France.

Supported by grant FP-2006/1A/I/009 to Dr. Leaños-Miranda from the Fondo para el Fomento de la Investigación (FOFOI)-IMSS, México. Dr. Ulloa-Aguirre is the recipient of a Research Career Development Award from the Fundación-IMSS, México.

G. Cárdenas-Mondragón, PhD; A. Ulloa-Aguirre, MD, DSc, Research Unit in Reproductive Medicine, Hospital de Ginecología y Obstetricia "Luis Castelazo Ayala," IMSS; I. Isordia-Salas, MD, Research Unit in Thrombosis, Hemostasia and Atherogenesis, Hospital Gabriel Mancera, IMSS; V. Goffin, PhD, Inserm, U808, Université Paris Descartes, Faculté de Médecine René Descartes, Centre de Recherche Croissance et Signalisation, Hopital Necker; A. Leaños-Miranda, MD, DSc, Research Unit in Reproductive Medicine, Hospital de Ginecología y Obstetricia "Luis Castelazo Ayala."

Address reprint requests to Dr. A. Leaños-Miranda, Research Unit in Reproductive Medicine, Hospital de Ginecología y Obstetricia "Luis Castelazo Ayala," Don Luis 111, Col. Nativitas, México 03500, DF, México. E-mail: alfredolm@yahoo.com

Accepted for publication March 19, 2007.