scholarly journals The Human Microbiome and Gender Medicine

2018 ◽  
Vol 2 (4) ◽  
pp. 123-127 ◽  
Author(s):  
Gali Levy ◽  
Ido Solt
Keyword(s):  
Diabetes Mellitus ◽  
Immune System ◽  
Autoimmune Disease ◽  
Microbial Communities ◽  
Molecular Genetics ◽  
Sex Hormones ◽  
Human Microbiome ◽  
Gender Medicine ◽  
Biological Sex ◽  
And Gender

Discoveries in molecular genetics over the last two decades have broadened our information about the genomics of complex microbial communities. As in all other fields of medicine, there is an undeniable need to explore the microbiome and the way it is impacted by biological sex. A number, although small, of recent studies have demonstrated that women and men have striking differences in the species that constitute their microbiomes. This effects pathological physiology in fields such as hepatology, oncology, autoimmune disease (most notably diabetes mellitus), autism, and obstetrics. There is still an unfortunate lack of research being done on the “microgenderome”: the interaction between microbiota, sex hormones, and the immune system. This review will highlight some of the main areas to be affected by microgenderome physiology, with an in depth focus on obstetrics.

scholarly journals Gender in Endocrine Diseases: Role of Sex Gonadal Hormones

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
R. Lauretta ◽  
M. Sansone ◽  
A. Sansone ◽  
F. Romanelli ◽  
M. Appetecchia
Keyword(s):  
Human Physiology ◽  
Sex Hormones ◽  
Medical Specialty ◽  
Gonadal Hormones ◽  
Response To Therapy ◽  
Endocrine Diseases ◽  
Biological Sex ◽  
New Frontier ◽  
And Gender ◽  
The Individual

Gender- and sex- related differences represent a new frontier towards patient-tailored medicine, taking into account that theoretically every medical specialty can be influenced by both of them. Sex hormones define the differences between males and females, and the different endocrine environment promoted by estrogens, progesterone, testosterone, and their precursors might influence both human physiology and pathophysiology. With the term Gender we refer, instead, to behaviors, roles, expectations, and activities carried out by the individual in society. In other words, “gender” refers to a sociocultural sphere of the individual, whereas “sex” only defines the biological sex. In the last decade, increasing attention has been paid to understand the influence that gender can have on both the human physiology and pathogenesis of diseases. Even the clinical response to therapy may be influenced by sex hormones and gender, but further research is needed to investigate and clarify how they can affect the human pathophysiology. The path to a tailored medicine in which every patient is able to receive early diagnosis, risk assessments, and optimal treatments cannot exclude the importance of gender. In this review, we have focused our attention on the involvement of sex hormones and gender on different endocrine diseases.

scholarly journals Cooperation and cheating as innovation: insights from cellular societies

2017 ◽  
Vol 372 (1735) ◽  
pp. 20160421 ◽  
Author(s):  
Athena Aktipis ◽  
Carlo C. Maley
Keyword(s):  
Immune System ◽  
Microbial Communities ◽  
Social Systems ◽  
Human Microbiome ◽  
Adaptive Immune System ◽  
The Body ◽  
Adaptive Immune ◽  
Constant Tension ◽  
Cellular Cooperation ◽  
Multicellular Organisms

The capacity to innovate is often considered a defining feature of human societies, but it is not a capacity that is unique to human societies: innovation occurs in cellular societies as well. Cellular societies such as multicellular bodies and microbial communities, including the human microbiome, are capable of innovation in response to novel opportunities and threats. Multicellularity represents a suite of innovations for cellular cooperation, but multicellularity also opened up novel opportunities for cells to cheat, exploiting the infrastructure and resources of the body. Multicellular bodies evolve less quickly than the cells within them, leaving them vulnerable to cellular innovations that can lead to cancer and infections. In order to counter these threats, multicellular bodies deploy additional innovations including the adaptive immune system and the development of partnerships with preferred microbial partners. What can we learn from examining these innovations in cooperation and cheating in cellular societies? First, innovation in social systems involves a constant tension between novel mechanisms that enable greater size and complexity of cooperative entities and novel ways of cheating. Second, cultivating cooperation with partners who can rapidly and effectively innovate (such as microbes) is important for large entities including multicellular bodies. And third, multicellularity enabled cells to manage risk socially, allowing organisms to survive in challenging environments where life would otherwise be impossible. Throughout, we ask how insights from cellular societies might be translated into new innovations in human health and medicine, promoting and protecting the cellular cooperation that makes us viable multicellular organisms. This article is part of the themed issue ‘Process and pattern in innovations from cells to societies’.

scholarly journals A General Theory of Autoimmune Disease Causation: Integrating Innate and Adaptive Immunity, Altered Antigen Processing, Sex and Genetic Predispositions, and Microbiome Effects

2019 ◽  
Author(s):  
Robert Root-Bernstein
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
Civil War ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Sex Hormones ◽  
Antigen Processing ◽  
Autoimmune Attack

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target.  Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection.  Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

scholarly journals Young FADOI and gender medicine: sex gender differences in cardiovascular disease

2018 ◽  
Vol 12 (1) ◽  
pp. 23 ◽  
Author(s):  
Tiziana Ciarambino ◽  
Miriam Gino ◽  
Paola Gnerre ◽  
Elena Barbagelata ◽  
Nunzia Barone ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Gender Differences ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Venous Thromboembolism ◽  
Arterial Hypertension ◽  
Gender Medicine ◽  
And Gender

We have evaluated gender-related differences in cardiovascular disease. In particular, in coronary heart disease, atrial fibrillation, arterial hypertension, venous thromboembolism and diabetes mellitus.

scholarly journals Is Diabetes Mellitus a Continuous Spectrum?

2011 ◽  
Vol 57 (2) ◽  
pp. 158-161 ◽  
Author(s):  
Barbara Brooks-Worrell ◽  
Jerry P Palmer
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Immune System ◽  
Autoimmune Disease ◽  
Classification Scheme ◽  
Current Classification ◽  
Similarities And Differences

BACKGROUND Diabetes mellitus has been historically divided into type 1 and type 2 diabetes, with type 1 being an autoimmune disease and type 2 being primarily a metabolic disease. CONTENT The current diabetes classification scheme needs to be reevaluated because of the accumulating evidence of immune system involvement in the pathophysiology of type 2 diabetes. SUMMARY There are similarities and differences between type 1 and type 2 diabetes with regard to pathogenesis, pathophysiology, and genetics. We propose a resolution to the dilemma of the current classification scheme.

scholarly journals The Association of Autoimmune Diseases with Type 1 Diabetes Mellitus in Children Depends Also by the Length of Partial Clinical Remission Phase (Honeymoon)

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Gulsum Ozen ◽  
Angela Zanfardino ◽  
Santino Confetto ◽  
Alessia Piscopo ◽  
Francesca Casaburo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Immune System ◽  
Autoimmune Disease ◽  
Type 1 Diabetes Mellitus ◽  
Clinical Remission ◽  
Insulin Production ◽  
Remission Phase ◽  
Type 1 Dm

Type 1 diabetes mellitus (DM) is characterized by irreversible, autoimmune, pancreatic β-cell destruction. During the disease, some patients experience a phase of Partial Clinical Remission (PCR) known as “honeymoon.” This is a transitory period that is characterized by insulin production by residual β cells following DM diagnosis and initiating the insulin therapy. In this study, we aimed to evaluate the influence of insulin production on immune system after the onset of diabetes, and we showed that the duration of honeymoon period could be related to the onset of other autoimmune conditions. For this retrospective study, 159 children aged between 11 and 18 years with type 1 DM were eligible. They have been diagnosed diabetes at least 10 years ago and use exogenous insulin. Our results showed that younger age at the onset of Type 1 DM in children, predicts Celiac Disease. Female sex and low HCO3 levels at the onset of DM had a high predictive value on patients who did not experience longer Partial Clinical Remission phase. Patients with higher BMI at the diagnosis of DM experienced shorter honeymoon period than the average. Smaller of our patients who diagnosed just DM have more than 297 days honeymoon period with respect to patients with one associated autoimmune disease. This may be due to a continuous and prolonged stimulation of immune system during the period of honeymoon that predispose the patient to develop other TH1 diseases. The patients who experienced more than 297 days Partial Clinical Remission seem under risk of developing one other autoimmune disease more than the patients who experienced less than 297 days Partial Clinical Remission. We have to consider that this observation is very intriguing because many protocols spring-up to try prolonging the honeymoon period in patients with autoimmune DM. If this aim is important from a metabolic point of view, long follow-ups are needed to be sure that the risk of other autoimmune diseases does not increase.

Pathway of Inflammation due to Asbestiform fiber "Fluoro-edenite" Exposure: an Update

2020 ◽  
Vol 16 ◽  
Author(s):  
Caterina Ledda ◽  
Claudia Lombardo ◽  
Elisabetta A. Tendi ◽  
Maria Hagnas ◽  
Gianluca Paravizzini ◽  
...  
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Early Response ◽  
The Body ◽  
Volcanic Area ◽  
Asbestos Fibers ◽  
Inflammatory Processes

: Fluoro-edenite (FE) is an asbestos-like amphibole present in the bentonitic lavas extracted from a stone quarry in Biancavilla, a village sited in the Etnean Volcanic Area (Italy). : Thoracic pathologies are the results of excessive inflammatory processes that are the early response of the immune system to inhaled fibers. As demonstrated for asbestos, fibers may trigger immune system cells in an acute and/or chronic manner. This review aims to clarify the pathways of inflammation in workers exposed to FE fibers. : Based on the articles reviewed, it seems that a permanent stimulus created by repeatedly inhaling the FE fibers and their persistence in the body can act as trigger both in promoting inflammatory processes and in immunological induction of autoimmune disease.

scholarly journals OP0307 A NOVEL TARGETED APPROACH TO ACHIEVE IMMUNE SYSTEM RESET: CD45-TARGETED ANTIBODY DRUG CONJUGATES AMELIORATE DISEASE IN PRECLINICAL AUTOIMMUNE DISEASE MODELS AND ENABLE AUTO-HSCT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 190-191
Author(s):  
G. Gillard ◽  
J. Proctor ◽  
S. Hyzy ◽  
O. Mikse ◽  
T. Lamothe ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune System ◽  
Autoimmune Disease ◽  
Disease Onset ◽  
Effector Function ◽  
Disease Models ◽  
Cell Transplant ◽  
Site Specific ◽  
Donor Chimerism ◽  
Multiple Sclerosis Patients

Background:Resetting the immune system through autologous hematopoietic stem cell transplant (autoHSCT) is a highly effective treatment in selected patients with autoimmune diseases. AutoHSCT can induce long-term remission with 80% progression free survival in multiple sclerosis patients (Muraro 2017, Burt 2019). Use of autoHSCT in scleroderma patients has achieved superior outcomes in two randomized studies compared to standard of care (Tyndall 2014, Sullivan 2018). These impressive results are achieved by a combination of the eradication of autoreactive immune effector cells and re-establishment of self-tolerance, i.e., immune system reset. However, only a small fraction of eligible patients undergo autoHSCT, largely due to toxicity associated with current conditioning protocols.Objectives:As part of our goal to enable more patients to benefit from immune system reset, we have generated novel anti-human CD45 ADCs that cross react with nonhuman primates (NHP) and an anti-mouse CD45 ADC to model the approach in mouse models of AID.Methods:The human-targeted CD45-ADC is an affinity-matured mAb that targets an epitope present on all human CD45 isoforms, is cross-reactive with NHP CD45, and is conjugated to a payload that efficiently kills both quiescent and cycling cells. This ADC is engineered to eliminate Fc-mediated effector function, enable site-specific conjugation of linker/payload, and enable rapid clearance. This ADC was evaluated in vitro and in vivo in hNSG and NHPs. The murine tool ADC specifically targets the CD45.2 isoform of mouse CD45, and is also engineered to eliminate effector function, allow for site-specific conjugation of linker payload, and be rapidly cleared. The payload for this murine tool ADC is potent and preferentially kills dividing cells. This ADC was tested for the ability to enable immune reset and ameliorate autoimmune disease in multiple disease models.Results:The anti-human CD45-ADC showed efficient killing of human HSCs and human and cyno PBMC, including CD3+cells from healthy donors and patients with MS. In hNSG, single doses of the CD45-ADC were well-tolerated and led to substantial depletion of human cells. In NHPs, single doses of CD45-ADC were well tolerated and depleted both peripheral lymphocytes and HSCs. Administration of a single dose of anti-human CD45-ADC to hNSGs with sclerodermatous xenoGVHD resulted in depletion of human T cells and resolution of symptoms. A single-dose of the anti-mouse CD45-ADC enabled full myeloablation and complete durable donor chimerism with congenic HSCT at 16 weeks. In a murine immunization model of MS, MOG-induced EAE, a single dose of the CD45-ADC followed by congenic HSCT prior to disease onset enabled full donor chimerism, significantly delayed disease onset and reduced disease severity. We are generating additional data in an adoptive transfer model of EAE to confirm and extend these results. In a murine model of arthritis, therapeutic treatment with a single dose of the CD45-ADC followed by congenic HSCT enabled complete donor chimerism and halted disease progression, comparable to with the effects of an anti-TNFα antibody. The ADC is being further evaluated in a model of type 1 diabetes and those data will be presented. These data demonstrate that CD45-ADC conditioning followed by congenic HSCT is sufficient for full myeloablation and immune reset.Conclusion:These results demonstrate that targeted immune depletion with a single dose of CD45-ADC can enable auto-HSCT and immune reset in multiple AID indications without toxic side effects. Targeted conditioning with CD45-ADC may represent a better tolerated approach for removing disease-causing cells as part of immune reset through auto-HSCT and enable more patients to benefit.Disclosure of Interests:Geoffrey Gillard Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Jennifer Proctor Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Sharon Hyzy Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Oliver Mikse Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Tahirih Lamothe Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Sean McDonough Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Nicholas Clark Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Rahul Palchaudhuri Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Anjali Bhat Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Melissa Brooks Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Ganapathy Sarma Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Prashant Bhattarai Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Pranoti Sawant Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Brad Pearse Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Charlotte McDonagh Shareholder of: Magenta Therapeutics, Employee of: Magenta Therapeutics, Tony Boitano Shareholder of: Magenta, Employee of: Magenta, Michael Cooke Shareholder of: Magenta, Employee of: Magenta

Sign in / Sign up

Export Citation Format

Share Document