Sabine Oertelt-Prigione

The influence of sex and gender on the immune response

The immune system and its orchestrated response are affected by a multitude of endogenous and exogenous factors, modulators and challenges. One of the most frequent differences described in the immune response is its vigor and activity in females compared to males, leading to the consequent increase in autoimmune conditions seen in the female population as well as differences in the immune response to pathogens and viruses. The following review summarizes our present knowledge on sex differences in the immune response, detailing the hormonal and genetic effects that have been proposed as explanatory mechanisms. Sexual hormones, mostly estrogen but also progesterone and testosterone, affect immune cells quantitatively and qualitatively. Relevant research has focused on the impact of hormones on cytokine production by the different effector cells, as well as impact on immunoglobulin production by B lymphocytes and activity of granulocytes and NK cells. The biological aspects are complemented by research data on the possible modulatory role of the X chromosome. In addition to biological differences, the frequently neglected role of gender as an immunomodulator is introduced and explored. Gender affects all areas of human life and consequently affects the different steps of an immune response. Exposure to various types of antigens, access to health promotion programs and health care, as well as prioritization of health needs and household resource allocation all affect the different response of females and males to immunologic challenges.

Sex and gender aspects in clinical medicine

Sex and gender aspects in clinical medicine / , Sex and gender aspects in clinical medicine / , کتابخانه دیجیتال جندی شاپور اهواز

Y chromosome loss in male patients with primary biliary cirrhosis.

Sex chromosome abnormalities have been advocated to be involved in the striking female prevalence of primary biliary cirrhosis (PBC) and women with PBC manifest an increased X chromosome loss in peripheral blood mononuclear cells compared to age-matched healthy women. Our knowledge of the etiopathogenesis of autoimmunity in male patients remains, however, limited. Next to the possible role of androgens and their imbalances, the Y chromosome appears as a potential candidate for influence of the immune function in men. Herein we analyzed a population of male patients with primary biliary cirrhosis (n = 26) and healthy controls (n = 88) to define a potential association of disease and the loss of the Y chromosome. We demonstrate that Y chromosome loss indeed is higher in PBC males compared to healthy controls, and this phenomenon increases with aging. We were, thus, able to confirm the existence of an analogous mechanism in the male population to previously identified X haploinsufficiency in female patients with organ-specific autoimmune disease. We propose that this commonality might represent a relevant feature in the etiopathogenesis of autoimmune diseases that should be further investigated.

Immunology and the menstrual cycle.

Sex and gender differences in disease prevalence, pathogenesis and modulation have been frequently reported. The menstrual cycle represents the opportunity to study the physiological effect of hormonal fluctuations in vivo on the immune function and chronic disease modulation. Reports on the effect of the cycle on immune cell numbers and activity fluctuations are scarce, but recent publications demonstrate an increasing interest in the subject. The menstrual cycle might affect immune cell numbers and modulate their activity throughout the 4-week cycle, as demonstrated in the case of regulatory T cells. The implications of these fluctuations are particularly relevant in the field of chronic diseases affecting women of reproductive age. In fact, baseline inflammation and immune cell activation in association with other mechanisms, such as regulation of receptor expression, modulation of muscular contraction and behavioral aspects might explain the menstrual-associated fluctuations described in chronic and acute diseases. In the following review the current knowledge about the modulatory effects of the menstrual cycle on both immune cells and systemic diseases, such as autoimmune diseases, asthma, diabetes, cardiac arrhythmia and schizophrenia, is reported. Most of these diseases display worsening of symptoms premenstrually or during menses due to physiologic effects on the target tissue mediated by progesterone and estrogen fluctuations and, thus, display paradigmatic changes potentially relevant to numerous other conditions.

Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines

BackgroundThe incorporation of sex and gender-specific analysis in medical research is increasing due to pressure from public agencies, funding bodies, and the clinical and research community. However, generations of knowledge and publication trends in this discipline are currently spread over distinct specialties and are difficult to analyze comparatively.MethodsUsing a text-mining approach, we have analysed sex and gender aspects in research within nine clinical subspecialties - Cardiology, Pulmonology, Nephrology, Endocrinology, Gastroenterology, Haematology, Oncology, Rheumatology, Neurology - using six paradigmatic diseases in each one. Articles have been classified into five pre-determined research categories - Epidemiology, Pathophysiology, Clinical research, Management and Outcomes. Additional information has been collected on the type of study (human/animal) and the number of subjects included. Of the 8,836 articles initially retrieved, 3,466 (39%) included sex and gender-specific research and have been further analysed.ResultsLiterature incorporating sex/gender analysis increased over time and displays a stronger trend if compared to overall publication increase. All disciplines, but cardiology (22%), demonstrated an underrepresentation of research about gender differences in management, which ranges from 3 to 14%. While the use of animal models for identification of sex differences in basic research varies greatly among disciplines, studies involving human subjects are frequently conducted in large cohorts with more than 1,000 patients (24% of all human studies).ConclusionsHeterogeneity characterizes sex and gender-specific research. Although large cohorts are often analysed, sex and gender differences in clinical management are insufficiently investigated leading to potential inequalities in health provision and outcomes.

X Monosomy in Female Systemic Lupus Erythematosus

Abstract:  Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, predominantly occurring in women of childbearing age. SLE, like several other autoimmune diseases, is characterized by a striking female predominance and, although sex hormone influences have been suggested as an explanation for this phenomenon, definitive data are still unavailable. Our group recently reported an increased X monosomy in lymphocytes of women, affected with primary biliary cirrhosis (PBC), systemic sclerosis (SSc), and autoimmune thyroiditis (AITD) in comparison to healthy women, thus suggesting the involvement of this chromosome in female predominance and in the deregulation of the immune system that characterizes autoimmunity. We have now evaluated X monosomy rates in SLE using fluorescence in situ hybridization (FISH) on peripheral mononuclear white blood cells (PBMCs) from female patients compared to healthy age‐matched controls. In addition, because of a previous finding of microchimerism as a pathogenetic cause of a number of autoimmune diseases, we investigated the presence of cells carrying the Y chromosome. We did not identify an increased X monosomy in women with SLE compared to controls (P= 0.3960, SLE vs. HCs, Students t‐test), thus suggesting that a different mechanism of immune deregulation might be predominant in the female population of patients with SLE.

Gender Aspects in Cardiovascular Pharmacology

The influence of biological sex on pharmacokinetics and pharmacodynamics has been previously described for each step of the metabolic cascade of pharmaceuticals. Women and men display differences in distribution, metabolism, and excretion of drugs for several biologic reasons. Estrogens are relevant in these processes, but cannot be regarded as the only responsible mechanism. Sex differences in the incidence of adverse drug reactions and pharmacotoxicity have also been reported for several classes of drugs and specifically for several cardiovascular preparations. Given the high incidence of cardiovascular conditions and thus the broad use of these drugs in the general population, these reports have to be considered of relevance to public health. Nonetheless, increased knowledge has not translated into the development and implementation of gender-specific pharmacologic guidelines which appear as the only effective strategy to minimize the incidence of sex-specific side effects and adverse drug reactions. In the present review, we analyze the basic aspects of sex-specific pharmacodynamics and present several examples of gender dimorphism in cardiovascular drugs. We also suggest measures to analyze and possibly improve current therapeutic strategies.

Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis

The immunomodulatory effects of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been elucidated at a cellular level and implicated in the pathogenesis of several complex diseases. Defects within the regulatory T cell compartment are one of the characteristics of primary biliary cirrhosis (PBC), an autoimmune chronic cholestatic liver disease, a phenotype that has also been shown in disease-mimicking animal models of this disease. We hypothesized that IDO dysregulation could lead to altered frequency and/or function of T cells at the level of antigen processing/presentation and we thus investigated IDO in peripheral monocytes and bile duct cells from patients with PBC. Both expression and activation manifested an impaired IFN-γ response in peripheral monocytes while a peculiar IDO expression profile in bile duct cells characterized early stage PBC. Further, we observed an increased frequency of a gain-of-function SNP within the TGF-β promoter region, a molecule known to suppress IDO transcription. In conclusion, we submit that an impaired IDO induction characterizes PBC and might represent a contributing factor in disease pathogenesis in association with several specific defects in the target tissue.

GenderMedDB: an interactive database of sex and gender-specific medical literature

BackgroundSearches for sex and gender-specific publications are complicated by the absence of a specific algorithm within search engines and by the lack of adequate archives to collect the retrieved results. We previously addressed this issue by initiating the first systematic archive of medical literature containing sex and/or gender-specific analyses. This initial collection has now been greatly enlarged and re-organized as a free user-friendly database with multiple functions: GenderMedDB (http://gendermeddb.charite.de).DescriptionGenderMedDB retrieves the included publications from the PubMed database. Manuscripts containing sex and/or gender-specific analysis are continuously screened and the relevant findings organized systematically into disciplines and diseases. Publications are furthermore classified by research type, subject and participant numbers. More than 11,000 abstracts are currently included in the database, after screening more than 40,000 publications. The main functions of the database include searches by publication data or content analysis based on pre-defined classifications. In addition, registrants are enabled to upload relevant publications, access descriptive publication statistics and interact in an open user forum.ConclusionsOverall, GenderMedDB offers the advantages of a discipline-specific search engine as well as the functions of a participative tool for the gender medicine community.

Sex and Gender in Medical Literature

While developing the general concept of this book, we were aware of a lack of a clear understanding of the concepts of sex and gender by many practicing medical professionals. On the one side, many of us have never been confronted with the issue during their studies or postgraduate training,1 on the other hand, the importance of the recognition of sex and gender as clinically relevant issues is only beginning to be acknowledged and for much time one had to intensively look for it in order to identify possible associations with health and disease.