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Sex differences & autoimmune disease

Arthritis in the hands

French researchers think that changes to the X chromosome in female mice could explain why women are more likely than men to be affected by autoimmune diseases.

Chromosomes determine the sex of an individual and the research investigated whether having an extra X chromosome (males have just one X chromosome) could be the reason why female mammals, including humans, are more susceptible to autoimmune diseases, such as arthritis – when an overactive immune system damages the body’s own tissues.

The team, led by the Centre national de la recherche scientifique (CNRS) and Paris Cité University, and also involving University Paul Sabatier and Sorbonne University, wanted to understand the link between a process known as ‘X-inactivation’, which happens during pregnancy, and autoimmune disease.

X-inactivation occurs in female embryos when most of the genes in one of the two X chromosome are switched off. This is done to prevent an unwanted ‘double dose’ of genes which can lead to abnormal development.

The team therefore produced genetically engineered female mice, without one of the genes responsible for X-inactivation, and saw that several genes on this inactive X chromosome, linked to the immune system, became reactivated as the mice grew to adulthood.

The animals also developed large spleens, which is a key symptom of the autoimmune disease lupus.

Céline Morey, at CNRS and Paris Cité University, said: “There are several indications that the same kind of regulation also occurs in humans. The X-chromosome inactivation process is conserved amongst all female eutherian mammals [mammals with a placenta].”


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