# The essential integration of sex and gender in immunological research

Marcus Altfeld, Camila Consiglio, Darragh Duffy, Molly Ingersoll, Cliona

O'Farrelly, Tal Pecht, Tal Shay, Helena Soares

► To cite this version:

Marcus Altfeld, Camila Consiglio, Darragh Duffy, Molly Ingersoll, Cliona O'Farrelly, et al.. The essential integration of sex and gender in immunological research. Immunology Letters, 2026, 277, pp.107097. 10.1016/j.imlet.2025.107097. pasteur-05451132

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# The essential integration of sex and gender in immunological research

Marcus Altfeld<sup>a,b,c,d</sup>, Camila Consiglio<sup>c</sup>, Darragh Duffy<sup>f</sup>, Molly Ingersoll<sup>g,h</sup>, Cliona O'Farrelly<sup>i,j</sup>, Tal Pecht<sup>k,l</sup>, Tal Shay<sup>m</sup>, Helena Soares<sup>n</sup>

## ARTICLE INFO

### Keywords:

Sex differences in immunity

Gender differences

Translational immunology

Precision medicine

Health equity

Scientific policy

Sex and gender are key factors influencing immune function, shaping immune responses, disease susceptibility, and treatment outcomes [1, 2]. Integrating sex and gender into immunological research is essential for advancing scientific understanding and improving healthcare for all individuals.

Sexual dimorphism is a fundamental characteristic of the immune system, with significant implications for human health [1,2]. Women generally exhibit stronger immune responses and better survival rates from infectious diseases, sepsis, trauma, and injury [1]. However, this heightened reactivity also increases their susceptibility to autoimmune diseases [1]. Men, by contrast, often experience higher mortality rates from severe infections and are more likely to develop a number of different types of cancer [1,3]. While biological and environmental mechanisms contribute to these sex and gender differences, further research is needed to fully understand these mechanisms and develop more effective prevention and treatment strategies for all individuals.

Neglecting sex and gender in immunological research limits our ability to provide effective and personalized medical treatments. Many medical interventions remain sex- and gender-blind, which can lead to variations in treatment efficacy and safety [4]. Furthermore, the exclusion of sex and gender considerations affects the reproducibility and applicability of scientific findings, slowing scientific progress [5]. Addressing these gaps will improve healthcare outcomes and foster a more inclusive approach to medical research [6].

We call for the following actions:

* Prioritize and expand research on sex and gender differences in immunity. Funding agencies, academic institutions, and scientific societies should explicitly require research investigating sex-based immunological mechanisms and their clinical implications.

* Mandate the systematic recording and analysis of sex in all biological studies and gender in all human studies. Including

<footnote><sup>a</sup> Institute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg 20251, Germany</footnote>

<footnote><sup>b</sup> Research Department Virus Immunology, Leibniz. Institute of Virology, Hamburg 20251, Germany</footnote>

<footnote><sup>c</sup> German Centre for Infectious Diseases Research, Leipzig, Germany</footnote>

<footnote><sup>d</sup> Leibniz-Institute of Virology, Leipzig, Germany</footnote>

<footnote><sup>e</sup> Systems Immunology Lab, Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, Lund, Sweden</footnote>

<footnote><sup>f</sup> Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France</footnote>

<footnote><sup>g</sup> Mucosal Inflammation and Immunity Team, Université Paris Cité, CNRS, Inserm, Institut Cochin, Paris, France</footnote>

<footnote><sup>h</sup> Department of Immunology, Institut Pasteur, Université Paris Cité, Paris, France</footnote>

<footnote><sup>i</sup> School of Medicine, Trinity College Dublin, Dublin, Ireland</footnote>

<footnote><sup>j</sup> School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland</footnote>

<footnote><sup>k</sup> Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany</footnote>

<footnote><sup>l</sup> Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany</footnote>

<footnote><sup>m</sup> Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel</footnote>

<footnote><sup>n</sup> Nova Medical School | Faculdade de Ciências Médicas, Nova University of Lisbon, Lisbon, Portugal</footnote>

<footnote>* Corresponding author.
E-mail address: talpecht@uni-bonn.de (T. Pecht).</footnote>
<table><caption>**Table 1**
Signatures for commitment statement.</caption><thead><tr><th>EFIS Member Society</th><th>Society Representative's Name</th><th>Signature (✓)</th></tr></thead><tbody><tr><td>Belgian Immunological Society (BIS)</td><td>Niels Hellings</td><td>✓</td></tr><tr><td>British Society for Immunology (BSI)</td><td>Tracy Hussell</td><td>✓</td></tr><tr><td>Czech Immunological Society (CIS)</td><td>Luca Vannucci</td><td>✓</td></tr><tr><td>Dutch Society for Immunology (NVvI)</td><td>Annemiek van Spriel</td><td>✓</td></tr><tr><td>European Federation of Immunological Societies (EFIS)</td><td>Bojan Polić</td><td>✓</td></tr><tr><td>Estonian Society for Immunology and Allergology (EIAS)</td><td>Kai Kisand</td><td>✓</td></tr><tr><td>French Society for Immunology (SFI)</td><td>Daniel Olive</td><td>✓</td></tr><tr><td>German Society for Immunology (DGfi)</td><td>Hansjörg Schild</td><td>✓</td></tr><tr><td>Hellenic Society of Immunology (HSI)</td><td>Katerina Tarassi</td><td>✓</td></tr><tr><td>Immunology Society of Slovenia (ISS)</td><td>Vladka Curin Serbec</td><td>✓</td></tr><tr><td>Israel Immunological Society (IIS)</td><td>Roi Gazit</td><td>✓</td></tr><tr><td>Romanian Society for Immunology (SIR)</td><td>Monica Neagu</td><td>✓</td></tr><tr><td>Russian Society for Immunology (RSI)</td><td>Totolian Areg A.</td><td>✓</td></tr><tr><td>Scandinavian Society for Immunology (SSI)</td><td>Stefanía P Bjarnarson</td><td>✓</td></tr><tr><td>Slovak Immunological Society (SIS)</td><td>Eva Kontseková</td><td>✓</td></tr><tr><td>Spanish Society for Immunology (SEI)</td><td>Silvia Sánchez Ramón</td><td>✓</td></tr><tr><td>Swiss Society for Allergology and Immunology (SSAI)</td><td>Camilli Ribi</td><td>✓</td></tr><tr><td>Turkish Society of Immunology (TSI)</td><td>İhsan Gursel</td><td>✓</td></tr><tr><td>The Irish Society for Immunology (ISI)</td><td>Joanne Lysaght</td><td>✓</td></tr></tbody></table>

these variables should be a standard requirement for study design, data analysis, and publication in immunology and biomedical sciences.

* **Develop and implement policies that integrate sex and gender considerations into clinical trials and therapeutic development.** Regulatory agencies and funding bodies should promote research that accounts for these differences to improve treatment outcomes for all individuals.

* **Encourage interdisciplinary collaboration to deepen our understanding.** Immunologists, geneticists, endocrinologists, epidemiologists, and social scientists should work together to explore the broader implications of sex and gender influences on immunity.

Recognizing and addressing sex and gender differences in immunology is essential for advancing scientific knowledge and improving medical care for all individuals. The European Societies of Immunology can play a crucial role in ensuring this important aspect of immunological research is prioritized, ultimately leading to more precise and effective healthcare solutions.

## Commitment statement

We invited leaders of immunological societies to join us in this commitment by signing this position letter (Table 1). By signing, they affirm the support for the integration of sex and gender considerations in immunological research and pledge to advocate for these principles within the respective organizations. Together, we can foster meaningful progress and ensure that immunological research reflects the diverse biological and societal factors influencing health outcomes.

## Authors clarifying statement

While it is important to note that studies involving both sexes as comparators are vital in medical research, this should not diminish the need for studies of diseases with sex-based predominance, such as cancer, where important differences in cancer incidence and immunotherapy outcomes also exist.

## CRediT authorship contribution statement

**Marcus Altfeld:** Conceptualization, Writing – original draft, Writing – review & editing. **Camila Consiglio:** Conceptualization, Writing – original draft, Writing – review & editing. **Darragh Duffy:** Conceptualization, Writing – original draft, Writing – review & editing. **Molly Ingersoll:** Conceptualization, Writing – original draft, Writing – review & editing. **Cliona O'Farrelly:** Conceptualization, Writing – original draft, Writing – review & editing. **Tal Pecht:** Conceptualization, Writing – original draft, Writing – review & editing. **Tal Shay:** Conceptualization, Writing – original draft, Writing – review & editing. **Helena Soares:** Conceptualization, Writing – original draft, Writing – review & editing.

## Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

The Study Group “Immune Sex Differences” acknowledges support from the European Federation of Immunological Societies (EFIS) for its activities. EFIS assisted in disseminating the position letter to the immunology community for endorsement but had no role in the conception, drafting, or approval of its content. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

## Acknowledgements

The Study Group “Immune Sex Differences” acknowledges support from the European Federation of Immunological Societies (EFIS) for its activities. EFIS assisted in disseminating the position letter to the immunology community for endorsement but had no role in the conception, drafting, or approval of its content.

## Appendix 1. - Definitions of sex and gender

The definitions of sex and gender that are addressed in the position letter are as previously described [7].

**Sex** refers to a set of biological attributes in humans and animals that are associated with physical and physiological features including chromosomes, gene expression, hormone function and reproductive/sexual anatomy. Sex is usually categorized as female or male, although there is variation in the biological attributes that constitute sex and how those attributes are expressed.

**Gender** refers to the socially constructed roles, behaviours and identities of female, male and gender diverse people. It influences how people perceive themselves and each other, how they behave and interact and the distribution of power and resources in society. Gender is usually incorrectly conceptualized as a binary (female/male) factor. In reality, there is a spectrum of gender identities and expressions defining how individuals identify themselves and express their gender.

## References

[1] S.L. Klein, K.L. Flanagan, Sex differences in immune responses, Nat. Rev. Immunol 16 (10) (2016 Oct) 626–638.

[2] S.P. Dias, M.C. Brouwer, D. Van De Beek, in: A.R. Richardson (Ed.), Sex and Gender Differences in Bacterial Infections, Sex and Gender Differences in Bacterial Infections, 90, Infect Immun, 2022 Oct 20 editore00283-22.

[3] A. Clocchiatti, E. Cora, Y. Zhang, G.P. Dotto, Sexual dimorphism in cancer, Nat. Rev. Cancer 16 (5) (2016 May) 330–339.

[4] N.C. Woitowich, A. Beery, Woodruff T. A 10-year follow-up study of sex inclusion in the biological sciences, eLife 9 (2020 June 9) e56344.
[5] J.A. Clayton, F.S. Collins, Policy: NIH to balance sex in cell and animal studies, Nature 509 (7500) (2014 May) 282-283.

[6] S. Haupt, C. Carcel, R. Norton, Neglecting sex and gender in research is a public-health risk, Nature 629 (8012) (2024 May 16) 527-530.

[7] S. Heidari, T.F. Babor, P. De Castro, S. Tort, M. Curno, Sex and gender equity in research: rationale for the SAGER guidelines and recommended use, Res. Integr. Peer. Rev 1 (1) (2016 May 3) 2.