[Neuropsychiatric lupus and autoantibodies against ionotropic glutamate receptor (NMDAR)]. / Lupus neuropsychiatrique et auto anticorps dirigés contre le récepteur ionotrope activé par le glutamate (R-NMDA).

Almost half of lupus patients will experience neuropsychiatric symptoms during the course of their disease. The etiology of the neuronal damages is still uncertain and probably multiple. Autoantibodies reactive with brain have been postulated to play a role. The observation of pathogenic autoantibodies binding the NR2A and NR2B subunits of the ionotropic glutamate receptor (NMDAR) illustrates this hypothesis. First studies showed that 40% of lupus patients possess serum titers of anti-NR2A/B antibody, but the presence of these autoantibodies is not always associated with the occurrence of neuronal damages or neuropsychiatric symptoms. Nevertheless, their presence is observed in the cerebrospinal fluid (CSF) of one half of the patients suffering from neurolupus. The presence in the serum of these autoantibodies anti-NR2A/B of the NMDAR is preliminary to their presence in the CSF where their deleterious effect is observable. Their entry into the brain is dependent on a breach of the blood brain barrier (BBB). In conclusion, the serum titer of autoantibodies against NR2A/B subunits is an indication of the potential for neuropsychiatric manifestations during the course of the disease.

Hormonal regulation of B-cell function and systemic lupus erythematosus.

The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males and numerous investigations to understand this gender bias have been performed, which propose as casual actors genetic predispositions and sex hormones effects. We will describe in this review how the sex hormones estrogen and prolactin influence B cell maturation and selection, permitting B cells to mature to immunocompetence in a mouse model of lupus. Finally, we will discuss the relevance and implications of these results for human disease.

Sex hormones and SLE: influencing the fate of autoreactive B cells.

The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males and numerous investigations to understand this gender bias have been conducted. While it is plausible that some sex-linked genes may contribute to the genetic predisposition for the disease, other likely culprits are the sex hormones estrogen and prolactin. In this chapter we review studies that have addressed the influence of sex hormones in SLE activity and discuss the recent data established in a BALB/c mouse transgenic for the heavy chain of an anti-DNA antibody. These mice are prone to develop lupus following exposure to exogenous sex hormones. We describe how estrogen and prolactin influence B cell maturation and selection, permitting B cells to mature to immunocompetence. Finally, we discuss the relevance and implications of these data for human disease.