Sex differences in immunity

Lotter, Hanna; Altfeld, Marcus

doi:10.1007/s00281-018-00728-x

Cited by 66 publications

(49 citation statements)

References 12 publications

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“…A number of identified genes in our study are expressed in immune cells, not surprising given the substantial sex differences in development and functioning of immune cells and autoimmunity (73,74). In fact, among the strongest results for MDD was a locus spanning ZNF385C, which is implicated in transcriptional regulation (75) and immune-related phenotypes via enhancers (i.e.…”

Section: Several Mechanisms Could Account For Opposite Direction Intementioning

confidence: 75%

Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders

Blokland¹,

Grove²,

Chen³

et al. 2020

Preprint

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BACKGROUND: Sex differences in the incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across these disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (GxS) interaction analysis of risk for these disorders, using data from 85,735 cases (33,403 SCZ, 19,924 BIP, 32,408 MDD) and 109,946 controls from the Psychiatric Genomics Consortium (PGC) and iPSYCH. RESULTS: Across disorders, genome-wide significant SNP-by-sex interaction was detected for a locus encompassing NKAIN2 gene (rs117780815; p=3.2x10-8), that interacts with sodium/potassium-transporting ATPase enzymes important for neuronal excitability. Three additional loci showed evidence (p<1x10-6) for cross-disorder GxS interaction (rs7302529, p=1.6x10-7; rs73033497, p=8.8x10-7; rs7914279, p=6.4x10-7) with various potential functions. Gene-based analyses identified GxS interaction across disorders (p=8.97x10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a locus in the MOCOS gene (rs11665282; p=1.5x10-7), implicating vascular endothelial cells. Secondary analysis of the SCZ PGC dataset detected a noteworthy interaction (rs13265509; p=1.1x10-7) in a locus containing IDO2, a kynurenine pathway enzyme with an immunoregulatory function previously implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant GxS of genes regulating vascular endothelial growth factor (VEGF) receptor signaling in MDD (pFDR<0.05). CONCLUSIONS: In the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway enrichment levels.

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Section: Several Mechanisms Could Account For Opposite Direction Intementioning

confidence: 75%

Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders

Blokland¹,

Grove²,

Chen³

et al. 2020

Preprint

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“…Sex hormones are an important biological factor contributing to the gender-bias in the immune response, and can influence outcomes of disease severity in infections and autoimmunity ( 4 , 88 – 90 ). Variations in sex hormone levels throughout the lifespan as with puberty, pregnancy, exogenous sex-hormone therapies, aging/menopause, and in transgender individuals modulate the immune response to pathogens therefore underlying the importance of their study.…”

Section: Immune Responsementioning

confidence: 99%

What’s Sex Got to Do With COVID-19? Gender-Based Differences in the Host Immune Response to Coronaviruses

et al. 2020

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The novel severe acute respiratory syndrome coronavirus 2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has ravaged the world, with over 22 million total cases and over 770,000 deaths worldwide as of August 18, 2020. While the elderly are most severely affected, implicating an age bias, a striking factor in the demographics of this deadly disease is the gender bias, with higher numbers of cases, greater disease severity, and higher death rates among men than women across the lifespan. While pre-existing comorbidities and social, behavioral, and lifestyle factors contribute to this bias, biological factors underlying the host immune response may be crucial contributors. Women mount stronger immune responses to infections and vaccinations and outlive men. Sex-based biological factors underlying the immune response are therefore important determinants of susceptibility to infections, disease outcomes, and mortality. Despite this, gender is a profoundly understudied and often overlooked variable in research related to the immune response and infectious diseases, and it is largely ignored in drug and vaccine clinical trials. Understanding these factors will not only help better understand the pathogenesis of COVID-19, but it will also guide the design of effective therapies and vaccine strategies for gender-based personalized medicine. This review focuses on sex-based differences in genes, sex hormones, and the microbiome underlying the host immune response and their relevance to infections with a focus on coronaviruses.

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“…This would result in an increased frequency of inflammatory and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis and reduced parasitic infections in females. These are some of the visible influences of sex disparities on outcomes and clinical manifestations of immune mediated diseases [16]. Females in general mount a vigorous immune response to vaccination, infections, and some malignancies [17].…”

Section: Hormones Chromosomes Immunity and Allergymentioning

confidence: 99%

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Martinis

Sirufo

Suppa

et al. 2020

IJMS

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Allergies are rapidly worsening in recent decades, representing the most common immunological diseases. The mechanism of disorders such as asthma, rhinocongiuntivitis, urticaria, atopic dermatitis, food and drug allergies, and anaphylaxis still remain unclear and consequently treatments is mostly still symptomatic and aspecific while developments of new therapies are limited. A growing amount of data in the literature shows us how the prevalence of allergic diseases is different in both sexes and its changes over the course of life. Genes, hormones, environmental and immunological factors affect sex disparities associated with the development and control of allergic diseases, while they more rarely are considered and reported regarding their differences related to social, psychological, cultural, economic, and employment aspects. This review describes the available knowledge on the role of sex and gender in allergies in an attempt to improve the indispensable gender perspective whose potential is still underestimated while it represents a significant turning point in research and the clinic. It will offer insights to stimulate exploration of the many aspects still unknown in this relationship that could ameliorate the preventive, diagnostic, and therapeutic strategies in allergic diseases.

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Sex differences in immunity

Cited by 66 publications

References 12 publications

Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders

Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders

What’s Sex Got to Do With COVID-19? Gender-Based Differences in the Host Immune Response to Coronaviruses

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

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