The implications of autoimmunity and pregnancy. J Autoimmun 34:J287-J299

Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
Journal of Autoimmunity (Impact Factor: 8.41). 05/2010; 34(3):J287-99. DOI: 10.1016/j.jaut.2009.11.015
Source: PubMed


There are multiple epidemiological studies that document the potential adverse affects of autoimmunity on nearly every aspect of reproduction, even in the absence of clinically manifest autoimmune disease. Two decades ago, it was suggested that women with autoimmune diseases avoid pregnancy due to inordinate risks to the mother and the child. In contrast, newer epidemiological data demonstrated that advances in the treatment of autoimmune diseases and the management of pregnant women with these diseases have similarly improved the prognosis for mother and child. In particular, if pregnancy is planned during periods of inactive or stable disease, the result often is giving birth to healthy full-term babies without increased risks of pregnancy complications. Nonetheless, pregnancies in most autoimmune diseases are still classified as high risk because of the potential for major complications. These complications include disease exacerbations during gestation and increased perinatal mortality and morbidity in most autoimmune diseases, whereas fetal mortality is characteristic of the anti-phospholipid syndrome (APS). In this review, we will discuss these topics, including issues of hormones, along with potential long-term effects of the microchimerism phenomenon. With respect to pregnancy and autoimmune diseases, epidemiological studies have attempted to address the following questions: 1) Is it safe for the mother to become pregnant or are there acute or chronic effects of pregnancy on the course of the disease? 2) Does the disease alter the course and/or the outcome of a pregnancy and thereby represent an inordinate risk for the fetus and infant? And do new therapeutic and management approaches improve the pregnancy outcomes in women with autoimmune diseases? 3) Does passage of maternal autoantibodies represent a risk to the child? 4) Do pregnancy, parity, or other factors influencing hormonal status explain the female predominance of many autoimmune diseases, and is the pregnancy effect related to microchimerism? Answering these questions has taken on additional importance in recent decades as women in western countries now frequently choose to delay pregnancies and have some or all of their pregnancies after disease onset. In this paper, we primarily focus on APS, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), and type 1 diabetes (T1D).

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Available from: Stanley M Naguwa
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    • "We found a high rate of fetal loss history. This rate is declining in western series as being spent these past 40 years from 43% to 17% [1][7][15], similar to that of the general population of non lupus women which lies between 10% and 15%[3][7]. Our average number of PNV seems low and inadequate for monitoring this type of high-risk pregnancies. "

    Preview · Article · Jan 2015 · Open Journal of Obstetrics and Gynecology
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    • "In particular, for estrogens, on one hand, the hypothesis that the induction of autoimmune diseases is associated with E2 exposure is supported by the observation that the incidence of some autoimmune diseases (e.g., systemic lupus erythematosus (SLE) and multiple sclerosis) increases after puberty and flares are more common during the pre-menstrual period and pregnancy [62]. Conversely, other autoimmune diseases arise at different ages and reproductive phases (in some cases following menopause, e.g., Sjogren syndrome [63]), even in the presence of gonadal dysgenesis (e.g., mixed connective tissue disease [64]), while the high estrogen levels characterizing pregnancy are often associated with an amelioration of clinical severity (e.g., rheumatoid arthritis [65]). Thus, it could be conceivable that autoimmune diseases are multifactorial entities and although estrogen may have a strong influence on the predisposition of women to autoimmune diseases, there is enough evidence that other environmental and genetic factors are important as well. "
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    ABSTRACT: The involvement of estrogens, which influence many physiologic processes, has been shown in the development or progression of several diseases including some cancers, most notably breast cancer, and autoimmune disorders. Estrogenic signal is transferred via estrogen receptors (ER) which have dual localization, predominantly intracellular but also in plasma membrane. The discovery of membrane-associated ER (mER) has greatly expanded our understanding of estrogen action; upon ligand binding, mER rapidly activate different signaling pathways inducing downstream transcription factors. Some target genes of the mER pathway may be activated independently of the intracellular ER. Additionally, intracellular ER action can be modulated by mER-initiated signaling. Most notably, the identification of autoantibodies reacting with ER (ERAB) and their possible pathogenic role in autoimmunity and cancer have opened a new path for the research in the estrogen-related receptor activity. In this review, we briefly recapitulate the localization and function of ER and mostly discuss the possible role of ERAB as novel potential prognostic and/or predictive tools in autoimmunity and cancer.
    Full-text · Article · Jul 2014 · The Journal of Steroid Biochemistry and Molecular Biology
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    • "For CD, the activity of disease was significantly lower during pregnancy as determined by the Harvey-Bradshaw index (Agret et al., 2005). In MS (Borchers et al., 2010; Confavreux et al., 1998; McCombe and Greer, 2013b), and RA (Hench, 1983; Nelson and Ostensen, 1997; Ostensen and Villiger, 2007) however, it is widely accepted that pregnancy is associated with the remission of symptoms, although there can be a flare of disease post-partum. In contrast to MS and RA, SLE an antibody mediated disease, is reported to worsen during pregnancy (Ruiz-Irastorza et al., 1996; Stojan and Baer, 2012), and this can vary in the degree of severity (Lateef and Petri, 2012). "
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    ABSTRACT: Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. In this review, we consider gender differences in systemic and organ-specific autoimmune diseases, and we summarize human data that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed. We discuss possible mechanisms for sex specific differences including gender differences in immune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones, genetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a significant influence on the development of autoimmune disease. Thus, considerations of gender should be at the forefront of all studies that attempt to define mechanisms that underpin autoimmune disease.
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