Could the Second X Chromosome Help Explain Why Autoimmune Diseases Disproportionately Affect Women?

Females are almost twice as likely as males to be diagnosed with an autoimmune disease (1).

Researchers at the University of Pennsylvania have found clues that the female (extra) X chromosome is involved. To understand their discovery, we must start with the basics.

You have 23 chromosomes from your biological mother and 23 from your biological father, or two copies of every gene.

However, males technically don't have two copies of EVERY gene.

The Y chromosome is nearly half the size of the X chromosome (XY - male sex chromosomes), whereas females have two X chromosomes (XX). This means females have an extra (second) copy of numerous X chromosome genes that males don't have.

Preventing these extra X chromosome genes from being turned on is extremely important.

In fact, there is a mechanism in females called X inactivation that silences one copy of each gene found on the extra X chromosome. This ensures that cells receive the appropriate dose of specific X chromosome gene products.

Back to the discovery.

Researchers found that X chromosome inactivation is regulated differently in the white blood cells that make (auto)antibodies (B cells).

They find that chronic inflammation can cause X chromosome inactivation to fail in antibody-producing cells. This can cause a second, extra copy of genes to be expressed.

One such X gene encodes a receptor involved in the innate immune response to infections, toll-like receptor 7 (TLR7).

Mimicking this failure to inactivate X chromosome genes in animal models worsened lupus-like disease.

Could this explain why autoimmunity is more prevalent in women? Let us know what you think by dropping a comment below.

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