Gender-Specific Impact of Sex Hormones on the Immune System

Sciarra, Francesca; Campolo, Federica; Franceschini, Edoardo; Carlomagno, Francesco; Venneri, Mary Anna

doi:10.3390/ijms24076302

Cited by 43 publications

(23 citation statements)

References 91 publications

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“…According to our findings, females had higher median concentrations of SARS-CoV-2 antibodies than males. This supports the theory that after disease exposure, females have higher antibody production compared to males because male androgens suppress the immune response (40). Contrary to our findings, several other studies have found that male HCWs have higher SARS-CoV-2 antibodies than female HCWs, inferring to behavioural differences (25,27,37,41,42).…”

Section: Discussionsupporting

confidence: 79%

Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania

Ibrahim,

Anthony,

Mshana

et al. 2024

Preprint

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Background: Health Care Workers (HCWs) have been playing crucial role in treating patient with COVID-19. They have a higher occupational risk of contracting the disease than the general population, and a greater chance of them transmitting the disease to vulnerable patients under their care. Given their scarcity and low COVID-19 vaccine acceptance in Africa, it is essential that HCWs are seroprotected and their exposure to COVID-19 minimized. This study was therefore designed to determine IgG antibody response to SARS-CoV-2 among HCWs in North Eastern, Tanzania. Methodology: This was a cross-sectional study carried out among 273 HCWs at Kilimanjaro Christian Medical Centre (KCMC), a tertiary, zonal referral hospital in Tanzania's North Eastern region. Stratified sampling was used to select study participants. Data were obtained from each consenting participant using a validated questionnaire. Blood samples were collected for SARS-CoV-2 IgG antibodies quantification by using an indirect ELISA test. RedCap software was used to enter and manage data. Statistical analysis was done by using STATA statistical software version 15 and GraphPad Prism v 9.0. A p-value of < 0.05 was considered the cut-off for statistical significance. Results: Among 273 HCWS only 37.9 % reported to have received COVID-19 vaccine. Except for one person, all of the participants had SARS-CoV-2 IgG antibody concentrations that were positive, with 64.5% of them having strong seropositivity. Female gender, allied health professionals, active smoking, COVID-19 patient interactions, COVID-19 vaccination receptivity, and adherence to recommended hand hygiene were found to be significant predictors of variation of median SARS-CoV-2 antibody concentration. The usage of personal protective equipment, history of previously testing PCR positive for COVID-19, the number of COVID-19 patient exposure and age were found to cause no significant variation in median antibody concentration among participants. Conclusions: This study reports a high seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Kilimanjaro Christian Medical Centre. This suggests that HCWs have significant exposure to SARS-CoV-2 despite the low rate of vaccination acceptance even among HCWs. We recommend a strengthened Infectious Prevention and Control (IPC) in hospitals through provision of technical leadership and coordination according to WHO guidelines. We also recommend continued conduction of seroprevalence studies to estimate the magnitude and trends of SARS-CoV-2 infections in different populations in Tanzania. A better understanding of the past, current, and future transmission patterns of infectious pathogens is critical for preparedness and response planning, and to inform the optimal implementation of existing and novel interventions under the current and changing climate.

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Section: Discussionsupporting

confidence: 79%

Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania

Ibrahim,

Anthony,

Mshana

et al. 2024

Preprint

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“…Sex hormones can affect the immune system, and there is a strong link between the gut microbiome and the immune system 21 . Changes in sex hormones may affect the immune system's response, 53 which in turn affects the balance of the gut microbiome. For example, sex hormones can affect the activity of immune cells, which can have an effect on the intestinal immune system.…”

Section: Discussionmentioning

confidence: 99%

“…Sex hormones can affect the immune system, and there is a strong link between the gut microbiome and the immune system. 21 Changes in sex hormones may affect the immune system's response, 53 which in turn affects the balance of the gut microbiome.…”

Section: F I G U R Ementioning

confidence: 99%

Causal relationship between gut microbiome and sex hormone‐binding globulin: A bidirectional two‐sample Mendelian randomization study

Yan,

Zheng,

Xia

et al. 2024

American J Rep Immunol

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ProblemCurrently, there is a variety of evidence linking the gut microbiota to changes in sex hormones. In contrast, the causal relationship between SHBG, a carrier of sex hormones, and the gut microbiota is unclear.Method of StudyBidirectional two‐sample Mendelian randomization (MR) analysis was used to detect the causal effect between SHBG and the gut microbiome. Summary statistics of genome‐wide association studies (GWASs) for the gut microbiome and SHBG were obtained from public datasets. Inverse‐variance weighting (IVW), weighted median, weighted mode, MR‐Egger and simple mode methods were used to operate the MR analysis. F‐statistics and sensitivity analyses performed to evaluate bias and reliability.ResultsWhen we set gut microbiome as exposure and SHBG as outcome, we identified nine causal relationships. In males, Coprobacter (PIVW = 2.01 × 10−6), Ruminococcus2 (PIVW = 3.40 × 10−5), Barnesiella (PIVW = 2.79 × 10−2), Actinobacteria (PIVW = 3.25 × 10−2) and Eubacterium fissicatena groups (PIVW = 3.64 × 10−2) were associated with lower SHBG levels; Alphaproteobacteria (PIVW = 1.61 × 10−2) is associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 9.75 × 10−3) and Defluviitaleaceae UCG011 (PIVW = 3.67 × 10−2) were associated with higher SHBG levels; Victivallaceae (PIVW = 2.23 × 10−2) was associated with lower SHBG levels. According to the results of reverse MR analysis, three significant causal effect of SHBG was found on gut microbiota. In males, Dorea (PIVW = 4.17 × 10−2) and Clostridiales (PIVW = 4.36 × 10−2) were associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 7.44 × 10−4) was associated with higherr SHBG levels. No signifcant heterogeneity of instrumental variables or horizontal pleiotropy was found in bidirectional two‐sample MR analysis.ConclusionsThis study may provide new insights into the causal relationship between the gut microbiome and sex hormone‐binding protein levels, as well as new treatment and prevention strategies for diseases such as abnormal changes in sex hormones.

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“…Previous studies also link SARS-CoV-2 infection and members of the Herpesviridae Family to AD development through modulation of AD-related processes via virus-host protein-protein interactions ( 67 , 68 ). Women generally exhibit stronger immune responses, making them more effective at fighting infections ( 69 ), but potentially increasing susceptibility to immune-mediated diseases ( 70 ). Sex hormones, particularly estrogen in women, modulate immune cell function ( 71 , 72 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis reveals sex-specific patterns in the hippocampus in Alzheimer’s disease

Onisiforou,

Christodoulou,

Zamba-Papanicolaou

et al. 2024

Front. Endocrinol.

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BackgroundThe hippocampus, vital for memory and learning, is among the first brain regions affected in Alzheimer’s Disease (AD) and exhibits adult neurogenesis. Women face twice the risk of developing AD compare to men, making it crucial to understand sex differences in hippocampal function for comprehending AD susceptibility.MethodsWe conducted a comprehensive analysis of bulk mRNA postmortem samples from the whole hippocampus (GSE48350, GSE5281) and its CA1 and CA3 subfields (GSE29378). Our aim was to perform a comparative molecular signatures analysis, investigating sex-specific differences and similarities in the hippocampus and its subfields in AD. This involved comparing the gene expression profiles among: (a) male controls (M-controls) vs. female controls (F-controls), (b) females with AD (F-AD) vs. F-controls, (c) males with AD (M-AD) vs. M-controls, and (d) M-AD vs. F-AD. Furthermore, we identified AD susceptibility genes interacting with key targets of menopause hormone replacement drugs, specifically the ESR1 and ESR2 genes, along with GPER1.ResultsThe hippocampal analysis revealed contrasting patterns between M-AD vs. M-controls and F-AD vs. F-controls, as well as M-controls vs. F-controls. Notably, BACE1, a key enzyme linked to amyloid-beta production in AD pathology, was found to be upregulated in M-controls compared to F-controls in both CA1 and CA3 hippocampal subfields. In M-AD vs. M-controls, the GABAergic synapse was downregulated, and the Estrogen signaling pathway was upregulated in both subfields, unlike in F-AD vs. F-controls. Analysis of the whole hippocampus also revealed upregulation of the GABAergic synapse in F-AD vs. F-controls. While direct comparison of M-AD vs. F-AD, revealed a small upregulation of the ESR1 gene in the CA1 subfield of males. Conversely, F-AD vs. F-controls exhibited downregulation of the Dopaminergic synapse in both subfields, while the Calcium signaling pathway showed mixed regulation, being upregulated in CA1 but downregulated in CA3, unlike in M-AD vs. M-controls. The upregulated Estrogen signaling pathway in M-AD, suggests a compensatory response to neurodegenerative specifically in males with AD. Our results also identified potential susceptibility genes interacting with ESR1 and ESR2, including MAPK1, IGF1, AKT1, TP53 and CD44.ConclusionThese findings underscore the importance of sex-specific disease mechanisms in AD pathogenesis. Region-specific analysis offers a more detailed examination of localized changes in the hippocampus, enabling to capture sex-specific molecular patterns in AD susceptibility and progression.

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Gender-Specific Impact of Sex Hormones on the Immune System

Cited by 43 publications

References 91 publications

Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania

Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania

Causal relationship between gut microbiome and sex hormone‐binding globulin: A bidirectional two‐sample Mendelian randomization study

Transcriptomic analysis reveals sex-specific patterns in the hippocampus in Alzheimer’s disease

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