Why women have more autoimmune diseases than men: An evolutionary perspective

Kronzer, Vanessa L.; Bridges, S. Louis; Davis, John M.

doi:10.1111/eva.13167

Cited by 71 publications

(32 citation statements)

References 71 publications

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“…In the few instances in which these patterns were reversed, those coincided with mice that had received an IGIP-encoding vaccine (serum IgA anti-Yamagata HAs in the FluB-RAM/IGIP and the FluB-att/IGIP groups, Fig 6D;nasal wash IgG anti-Yamagata HAs and IgG and IgA anti-NA in the FluB-RAM/IGIP group, Figs7C, E and F). A female bias with more consistent responses against heterologous Yamagata-lineage HA antigens agrees with the notion of women developing more cross-reactive and/or self-reactive antibodies44 . It is important to note that serum and NW samples obtained at 14 dpc are from different mice than serum samples obtained at 19 dpb, however biological sex bias and the impact of different FLUBV vaccine modi cations were consistently observed for both time points.…”

supporting

confidence: 82%

Modified Live Attenuated Influenza B Virus Vaccines and Sex-driven Differences on Humoral Immune Responses in the DBA/2J Mouse Model

Pérez¹,

Cardenas-Garcia²,

Cáceres³

et al. 2022

Preprint

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Influenza B virus (FLUBV) is a major respiratory pathogen of humans. Seasonal influenza vaccines include either one or both FLUBV lineage strains, Victoria, and Yamagata. Vaccine mismatch occurs frequently, particularly in countries where vaccines contain only one of the lineages. We have previously described the safety and efficacy of modified live attenuated FLUBV vaccines based on either virus with rearranged genomes (FluB-RAM and FluB-RANS) or carrying a PB1 segment with a combination of temperature sensitive mutations and a C-terminal HA tag (FluB-att). We compared side by side the immunological responses in female and male DBA/2J mice vaccinated with either one of these vaccines and those with isogenic backbones containing a chimeric HA segment carrying an N-terminal IgA inducing peptide (IGIP). Recombinant viruses with or without the IGIP modification were genetically stable over multiple passages in eggs. In mice, introduction of IGIP improved attenuation of the vaccine candidates, particularly for the FluB-RAM/IGIP compared with the non-IGIP FluB-RAM counterpart. In a prime-boost regimen, mice were completely protected against lethal challenge with a homologous FLUBV strain. Recombinant viruses induced neutralizing antibodies with hemagglutination inhibition titers ≥40. Antibodies against NA and NP were readily detected. Compared to male mice and regardless of the vaccine used, female mice showed a clear trend towards enhanced humoral and cross-reactive IgG and IgA anti-HA responses as well as against NA and NP. The presence of IGIP in the vaccine resulted in an overall trend towards reduced anti-HA responses but enhanced anti-NA and anti-NP responses, particularly of the IgA isotype. Mucosal and serological responses two weeks after challenge showed similar trends with clear differences observed based on sex, vaccine backbone, and whether the vaccine carried the IGIP modification. These findings are significant for the development of universal influenza vaccines.

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supporting

confidence: 82%

Modified Live Attenuated Influenza B Virus Vaccines and Sex-driven Differences on Humoral Immune Responses in the DBA/2J Mouse Model

Pérez¹,

Cardenas-Garcia²,

Cáceres³

et al. 2022

Preprint

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“…In the case of persistent COVID-19, the inflammation caused by the SARS-CoV2 infection of tissues would recruit B cells with EBV latency, where ectopic lymphoid aggregates could form and give rise to viral reactivations. Likewise, it could also help us to understand why the EBV-associated autoimmune diseases, long COVID-19, and chronic fatigue syndrome/myalgic encephalomyelitis are more common in women [ 290 , 291 , 292 , 293 , 294 , 295 ]. Estrogens, by increasing B-cell survival [ 66 ], would allow for a greater permanence of ectopic lymphoid aggregates with EBV latency in the inflamed tissues of patients with “ancestral” HLA-II alleles, and, therefore, a chronification of symptoms.…”

Section: Discussionmentioning

confidence: 99%

CD4+ Cytotoxic T Cells Involved in the Development of EBV-Associated Diseases

Ruiz-Pablos

2022

Pathogens

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Activated cytotoxic CD4 T cells (HLA-DR+) play an important role in the control of EBV infection, especially in cells with latency I (EBNA-1). One of the evasion mechanisms of these latency cells is generated by gp42, which, via peripherally binding to the β1 domain of the β chain of MHC class II (HLA-DQ, -DR, and -DP) of the infected B lymphocyte, can block/alter the HLA class II/T-cell receptor (TCR) interaction, and confer an increased level of susceptibility towards the development of EBV-associated autoimmune diseases or cancer in genetically predisposed individuals (HLA-DRB1* and DQB1* alleles). The main developments predisposing the factors of these diseases are: EBV infection; HLA class II risk alleles; sex; and tissue that is infiltrated with EBV-latent cells, forming ectopic lymphoid structures. Therefore, there is a need to identify treatments for eliminating cells with EBV latency, because the current treatments (e.g., antivirals and rituximab) are ineffective.

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“…At the epidemiological level, the hypothesis is supported by a connection between psychiatric and systemic autoimmune disorders [ 291 , 292 ]. Both psychiatric [ 293 ] and autoimmune disorders [ 294 ] also manifest more frequently in women, whose immune system is in general overactive, which has evolutionary bases. Various studies demonstrate that, e.g., schizophrenia, depression, suicidal ideation and post-traumatic stress disorder are characterized with increased levels of inflammatory markers, particularly IL-1β, IL-2R, IL-6, IL-17A, TNF-α and CRP [ 1 ].…”

Section: Maternal Immune Activation and Neuropsychiatric Disordersmentioning

confidence: 99%

Obesity and the Brain

Karczewski

Zielińska

Staszewski

et al. 2022

IJMS

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Innate and adaptive immunity are essential for neurodevelopment and central nervous system (CNS) homeostasis; however, the fragile equilibrium between immune and brain cells can be disturbed by any immune dysregulation and cause detrimental effects. Accumulating evidence indicates that, despite the blood–brain barrier (BBB), overactivation of the immune system leads to brain vulnerability that increases the risk of neuropsychiatric disorders, particularly upon subsequent exposure later in life. Disruption of microglial function in later life can be triggered by various environmental and psychological factors, including obesity-driven chronic low-grade inflammation and gut dysbiosis. Increased visceral adiposity has been recognized as an important risk factor for multiple neuropsychiatric conditions. The review aims to present our current understanding of the topic.

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Why women have more autoimmune diseases than men: An evolutionary perspective

Cited by 71 publications

References 71 publications

Modified Live Attenuated Influenza B Virus Vaccines and Sex-driven Differences on Humoral Immune Responses in the DBA/2J Mouse Model

Modified Live Attenuated Influenza B Virus Vaccines and Sex-driven Differences on Humoral Immune Responses in the DBA/2J Mouse Model

CD4+ Cytotoxic T Cells Involved in the Development of EBV-Associated Diseases

Obesity and the Brain

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