Stimulation of anti-RNP antibody binding to cultured keratinocytes by estradiol

Abstract

Antibodies to extractable nuclear antigens (ENA) are frequently demonstrated in the serum of patients with cutaneous lupus erythematosus. To gain a better understanding of the influence of sex hormones on cutaneous lupus, we investigated the in vitro binding of anti-ENA antibodies to cultured human keratinocytes. Estradiol-beta augmented the binding of anti-RNP, anti-SS-A/Ro, and anti-SS-B/La antibodies to cultured cells, but produced no enhancement of the binding of anti-Sm antibodies. In addition, we examined the effects of 16-alpha-hydroxyestrone, a highly estrogenic metabolite, on the binding of anti-ENA antibodies to cultured cells. This agent did not produce any augmentation of binding. Based on these experiments, we discuss the influence of estradiol on cutaneous lupus.

Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients

“…These data suggest that female sex hormones may have a role in the production of these autoantibodies. Indeed, Furukawa et al 23 demonstrated the enhanced binding of keratinocytes to anti-nRNP upon stimulation with β-oestradiol. We also observe a shift in the SLE sex bias of our population.…”

Adenovirus infection induces loss of HLA class I and CD3 antigens, but does not induce cell surface presentation of the La (SS-B) autoantigen

“…complexes with HLA class II molecules, thereby evoking an immune response. Indeed, several studies support the idea that autoantigens, or antigenic determinants thereof, become exposed at tiic cell surface during disturbance of normal ceil metabolism [11][12][13][14][15][16]. A major drawback of most of those studies is that they depend on immunoliuorescencc techniques only, and do not eompletely exclude the possibility that the presence of extracellular antigens results from leakage from datnaged cells.…”

The intracellular 52‐kd Ro/SSA autoantigen in keratinocytes is up‐regulated by tumor necrosis factor α via tumor necrosis factor receptor I

“…Several studies revealed that Ro/SSA autoantigens are expressed on the surface of keratinocytes, which are major sites of immunologic damage in photosensitive cutaneous lupus after exposure to stress factors such as ultraviolet (UV) light (10–13), estradiol (14, 15), cytotoxic prostaglandins (16), viral infections (17), oxidative stress (18), heat shock (19), and phorbol 12‐myristate 13‐acetate (19). Ro/SSA autoantigens are also present in larger apoptotic blebs (20).…”