The X-factor: Improving immunotherapy through X chromosome Research

Women have a more powerful immune system than men, a phenomenon significantly influenced by the X chromosome, which harbors numerous immune-related genes. Sanquin researcher Nila Servaas aims to elucidate the precise mechanisms behind this, and apply that to improve immunotherapy. Although this is a promising treatment, women experience side effects more frequently, because their immune system works more powerfully. Nila wants to find starting points to make immunotherapy more suitable for women, but also to improve it for men.

Women possess two X chromosomes (XX) whereas men have an X and a Y chromosome (XY). The Y chromosome contains relatively few genes compared to the X chromosome, and primarily governs male sexual development. A multitude of immune system-related genes reside on the X chromosome. To prevent women from getting a double dose of it, nature has arranged it so that one of the X chromosomes is switched off early in the embryonic development of girls. However, some genes on the silenced chromosome remain active. This contributes to a stronger immune system in women, affording them greater protection against viral infections and a stronger response to vaccinations. Conversely, women are also more susceptible to autoimmune diseases, in which the immune system erroneously attacks the body's own tissues.

Nila: "I aim to investigate which genes remain active on the inactivated X chromosome, and how they modulate the immune system. We want to use that knowledge to improve existing immunotherapy. For women and for men."

Only research on men

Nila notices that research is often only done on men. "I searched existing datasets and only came across data from men, or gender was not specified." She therefore wants to contribute to greater awareness of the difference between men and women in biomedical research.

Until recently, Nila was affiliated with the EMBL in Heidelberg (Germany), where she initially explored the X chromosome and wished to further investigate its influence on the immune system. To this end, she sought collaboration with Monika Wolkers, group leader at Sanquin. Nila has recently been awarded two grants: an LSBR Early Career grant and a Marie Skłodowska-Curie grant. She will use these to develop her own line of research at Sanquin. In the future, she hopes not only to better tailor immunotherapy to men or women, but also develop strategies to dampen the immune system in autoimmune diseases.