Sex Hormones in Acquired Immunity and Autoimmune Disease

Abstract

Women have stronger immune responses to infections and vaccination than men. Paradoxically, the stronger immune response comes at a steep price, which is the high incidence of autoimmune diseases in women. The reasons why women have stronger immunity and higher incidence of autoimmunity are not clear. Besides gender, sex hormones contribute to the development and activity of the immune system, accounting for differences in gender-related immune responses. Both innate and adaptive immune systems bear receptors for sex hormones and respond to hormonal cues. This review focuses on the role of sex hormones particularly estrogen, in the adaptive immune response, in health, and autoimmune disease with an emphasis on systemic lupus erythematosus.

Estrogen Reverses HDAC Inhibitor-Mediated Repression of Aicda and Class-Switching in Antibody and Autoantibody Responses by Downregulation of miR-26a

“…The effect of estrogen on the immune system can differ dependent on the level of estrogens, cell type, cell activation state, microenvironment, and the experimental context (9). Estrogen can have profound effects on B cell differentiation, activity, function, and survival (7,9,17). Our results further extend our previous findings and further emphasize an important role for estrogen in the regulation of AID expression and, therefore, the maturation of the antibody response.…”

“…Estrogen plays an important physiologic role in B cell development and function (4,17). E2 can induce a genetic program that alters B cell survival and activation in a B cell intrinsic fashion and thus skews the naïve immune system toward autoreactivity (3).…”

“…Estrogen plays an important role in boosting the production of mature antibodies and autoantibodies (1,2). This provides an explanation for the greater antibody response to microbial vaccines and infections as well as the greater incidence of antibody-mediated autoimmunity, such as systemic lupus erythematosus, in females (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Like protective antibodies against pathogenic microorganisms, pathogenic autoantibodies in humans and mice with systemic autoimmunity are generally class-switched and hypermutated, strongly suggest a role for estrogen in modulation of immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM).…”

“When sex influences the brain: implications for Alzheimer disease”

“…This interaction could be particularly complex, as there are aspects of AD pathogenesis for which the immune system can be beneficial (degradation of Aβ by microglia) as well as deleterious. In keeping with the potential contribution of the immune system to AD initiation and progression, as well as the relationship between neuropathologic lesion burden and clinical deficits, it is appropriate to also recall that autoimmune disorders, both those which affect the central nervous system exclusively (such as multiple sclerosis) as well as systemic disorders which may involve the brain (such as systemic lupus erythematosis) demonstrate sex-based differences in incidence rates [6,7]. Whether the underlying bases of this difference in inflammatory disease risk based on sex might contribute to differences in AD biomarkers and histologic findings needs further exploration.…”

<p>Towards Precision Medicine in Systemic Lupus Erythematosus</p>

“…Beside the endogenous factors (sex, age, hormones), it is also known that environmental factors (psychological stress, viral infections, smoking, chemicals, nutrition) influence the disease course and may trigger it. [2][3][4][5][6][7] Several sets of classification criteria have been developed. In 2012 Systemic Lupus International Collaborating Clinics (SLICC) developed a set of criteria 8 shown to have a higher sensitivity than the American College of Rheumatology's revised criteria (1997), 9 although with slighter lower specificity.…”