Almost 80% of autoimmune diseases occur in women. Why should this be?

From the evolutionarily standpoint, perhaps up regulation of immunity conferred a survival advantage. Women spent a much greater percentage of the time pregnant in Hunter gatherer days than they do at the present time, and an active immune system may have been an advantage in getting both you and your child’s genes through the many ancient environmental hurdles.

Women differ from men in the prominence of the X chromosome, the female sex hormones, estrogen and progesterone, and, surprisingly, in their microbiome. All three areas may play a role in autoimmunity.

The X chromosome contains many genes directly tied to Autoimmune diseases. One of these is a gene for TLR-7, which is important in the innate immune response, and is linked to disorders such as lupus and scleroderma. Another Gene, TASL, increases the production of interferon, a common inflammatory factor.

Many autoimmune diseases are driven by estrogen. For instance, estrogen attaches to, and turns on the gene that codes for interferon gamma. It activates B cells which produce antibodies. Progesterone, another female hormone is elevated in pregnancy, and tends to switch on the TH-2 response, which produces more antibodies. AIRE, the immune regulator itself, is partially influenced by the sex hormones.

A severe asthmatic I was treating became pregnant, and her asthma marvelously improved. I had always thought that pregnancy turned OFF her asthma-linked TH-2 response, going against one of the observations above.

At the present stage of knowledge, individuals may respond in perplexing ways to interleukins, treatments and pregnancy. Cellular interactions are complex indeed.

The microbiome in the male tends to increase testosterone, which tends to down regulate the immune system. The reverse is true for the female microbiome.

The fact that identical twins may be discordant with autoimmune disease favors environmental factors, such as the microbiome and other extrinsics such as smoking, diet, stress and chemicals. Some of the males who get autoimmune diseases tend to be feminized, such as in the Klinefelter syndrome, which has an extra extra X chromosome, and an XXY genotype.

The use of the estrogen or progesterone in the form of contraceptives tends to increase the likelihood of autoimmune diseases. The observation that women are more susceptible to autoimmune diseases goes along with many of these genetic, hormonal, and environmental observations.

Please consult for Scientific American, September, 2021, P 40 for more information.

—Dr. C.