Limits...
Sex differences in Sjögren's syndrome: a comprehensive review of immune mechanisms.

Brandt JE, Priori R, Valesini G, Fairweather D - Biol Sex Differ (2015)

Bottom Line: Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women.The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth.This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren's syndrome in order to gain a better understanding of disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205 USA ; Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy.

ABSTRACT
Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women. Sjögren's syndrome (SS) is an AD that occurs predominately in women over men (16:1). The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth. The disease is believed to be mediated by an inflammatory and autoantibody response directed against salivary and lacrimal gland tissues. This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren's syndrome in order to gain a better understanding of disease pathogenesis.

No MeSH data available.


Related in: MedlinePlus

Possible role of estrogen in promoting Sjögren’s syndrome. In the context of genetic, epigenetic, and environmental influences like infections and chemicals, the rapid decline in estrogen (E2) levels prior to menopause leads to reduced glandular cell health. Death of glandular cells via apoptosis/necrosis provides self-antigens like nuclear antigens for presentation to the immune system to promote autoimmune disease. At the same time, the protective effects of higher estrogen levels on inflammation disappear allowing increased activation of innate immune pathways like toll-like receptor 4 (TLR4) and NFκB. In contrast, low levels of estrogen continue to increase the level and different types of autoantibodies with age
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4630965&req=5

Fig1: Possible role of estrogen in promoting Sjögren’s syndrome. In the context of genetic, epigenetic, and environmental influences like infections and chemicals, the rapid decline in estrogen (E2) levels prior to menopause leads to reduced glandular cell health. Death of glandular cells via apoptosis/necrosis provides self-antigens like nuclear antigens for presentation to the immune system to promote autoimmune disease. At the same time, the protective effects of higher estrogen levels on inflammation disappear allowing increased activation of innate immune pathways like toll-like receptor 4 (TLR4) and NFκB. In contrast, low levels of estrogen continue to increase the level and different types of autoantibodies with age

Mentions: Female predominance and disease onset following a major stressful event and/or following menopause in SS patients suggest that the endocrine system and sex hormones are involved in the pathogenesis of disease [63]. Menopause is defined as the final menstrual period without another menstrual period for 12 months and occurs in Western cultures at 49–52 years of age [64]. Large decreases in estrogen (i.e., estradiol) occur in the last 6 months before menopause and thereafter, while testosterone gradually decreases with age in both sexes. Understanding how the menopausal transition affects inflammation is complicated by changes in the immune response that occur with aging. Autoantibodies continually increase with age in women [65–67]. Importantly, lower doses of estrogen present after menopause are still able to promote B cell proliferation and autoantibody production following menopause in women (Fig. 1). However, lower estrogen levels may reduce the protective, anti-inflammatory effects of estrogen (i.e., estrogen increases Treg and regulatory macrophages and inhibits proinflammatory NFκB) that were present prior to menopause and allow increased activation of TLR on innate immune cells resulting in elevated proinflammatory cytokines like TNF, IL-1β, and IFNs [7] (Fig. 1).Fig. 1


Sex differences in Sjögren's syndrome: a comprehensive review of immune mechanisms.

Brandt JE, Priori R, Valesini G, Fairweather D - Biol Sex Differ (2015)

Possible role of estrogen in promoting Sjögren’s syndrome. In the context of genetic, epigenetic, and environmental influences like infections and chemicals, the rapid decline in estrogen (E2) levels prior to menopause leads to reduced glandular cell health. Death of glandular cells via apoptosis/necrosis provides self-antigens like nuclear antigens for presentation to the immune system to promote autoimmune disease. At the same time, the protective effects of higher estrogen levels on inflammation disappear allowing increased activation of innate immune pathways like toll-like receptor 4 (TLR4) and NFκB. In contrast, low levels of estrogen continue to increase the level and different types of autoantibodies with age
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4630965&req=5

Fig1: Possible role of estrogen in promoting Sjögren’s syndrome. In the context of genetic, epigenetic, and environmental influences like infections and chemicals, the rapid decline in estrogen (E2) levels prior to menopause leads to reduced glandular cell health. Death of glandular cells via apoptosis/necrosis provides self-antigens like nuclear antigens for presentation to the immune system to promote autoimmune disease. At the same time, the protective effects of higher estrogen levels on inflammation disappear allowing increased activation of innate immune pathways like toll-like receptor 4 (TLR4) and NFκB. In contrast, low levels of estrogen continue to increase the level and different types of autoantibodies with age
Mentions: Female predominance and disease onset following a major stressful event and/or following menopause in SS patients suggest that the endocrine system and sex hormones are involved in the pathogenesis of disease [63]. Menopause is defined as the final menstrual period without another menstrual period for 12 months and occurs in Western cultures at 49–52 years of age [64]. Large decreases in estrogen (i.e., estradiol) occur in the last 6 months before menopause and thereafter, while testosterone gradually decreases with age in both sexes. Understanding how the menopausal transition affects inflammation is complicated by changes in the immune response that occur with aging. Autoantibodies continually increase with age in women [65–67]. Importantly, lower doses of estrogen present after menopause are still able to promote B cell proliferation and autoantibody production following menopause in women (Fig. 1). However, lower estrogen levels may reduce the protective, anti-inflammatory effects of estrogen (i.e., estrogen increases Treg and regulatory macrophages and inhibits proinflammatory NFκB) that were present prior to menopause and allow increased activation of TLR on innate immune cells resulting in elevated proinflammatory cytokines like TNF, IL-1β, and IFNs [7] (Fig. 1).Fig. 1

Bottom Line: Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women.The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth.This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren's syndrome in order to gain a better understanding of disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205 USA ; Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy.

ABSTRACT
Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women. Sjögren's syndrome (SS) is an AD that occurs predominately in women over men (16:1). The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth. The disease is believed to be mediated by an inflammatory and autoantibody response directed against salivary and lacrimal gland tissues. This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren's syndrome in order to gain a better understanding of disease pathogenesis.

No MeSH data available.


Related in: MedlinePlus