New Delhi: Women make up 80% of patients with major Autoimmune Rheumatic Diseases (AIRD). In certain diseases such as lupus, and Sjogren’s syndrome- females outnumber their male counterparts by a staggering 9:1 proportion. Autoimmune disease results from dysregulated activation of immune cells such as T and B cells attacking one’s body tissues. Women have higher levels of circulating antibodies, CD4+ T cells, and B cells in their blood, and develop more robust cytokine responses to infection. Because of this stronger immune response, females, in general, are better equipped to deal with infections/ tumours. However, this comes at a cost- An increase in the diseases resulting from the hyperactive immune system- AIRD.
Dr Abhishek Patil, HOD & Consultant – Rheumatology, Manipal Hospital Old Airport Road, Bengaluru, explained what makes women more vulnerable to arthritis.
“Initially this female predilection was thought to result from high levels of estrogens. Estrogen has a well-documented influence on the immune system, often enhancing the activity of certain immune cells, such as B cells and T cells, which play critical roles in immune responses. In contrast, male sex hormones like testosterone tend to have a suppressive effect on the immune system, which might account for the lower incidence of autoimmune diseases in men,” said Dr Patil.
“Recent advances in molecular genetics have put forth novel explanations for this AIRD preference towards female sex. Females have two “X” chromosomes, whereas males have one “X” + one “Y” chromosome. The X chromosome encodes about 1000 genes, many of which are involved in immunological pathways. During the development, one of the X chromosomes in females gets inactivated i.e. X chromosome Inactivation (XCI) to maintain a balance of genes. In theory, this occurs randomly resulting in mosaicism, so half the somatic cells in females should contain a paternal X chromosome and the other half should contain the maternally derived X chromosome. However, this XCI many a times incomplete- X chromosomal immune genes may escape XCI and thus deliver a higher dosage of these genes. Interestingly males with Klinefelter’s syndrome (Males with XXY) – have an equal risk of lupus/Sjogren’s as females,” the expert added.
Another postulated mechanism is that of Microchimerism. Females carry a fetus in their womb, which in essence is like a heterotypic transplant. The placenta separates fetal tissues from the maternal immune system thus maintaining an immune privilege status during pregnancy. However, during birth fetal cells and tissues can escape into maternal circulation. These fetal cells can initiate an immune response against the maternal tissues leading to a Graft versus host disease (GVHD) like picture. Thus, many autoimmune diseases increase following childbirth. This has been well-researched in diseases such as scleroderma, where pathophysiological aspects resemble GVHD.
Thus, the higher prevalence of autoimmune disease in females is due to the complex interplay of hormonal, genetic, immune system, and environmental factors. Estrogens, X chromosomal immune gene overdosage, and the presence of fetal tissue in the maternal circulation could all serve as predictors of autoimmunity in females.
The higher prevalence of autoimmune disease in females is due to the complex interplay of hormonal, genetic, immune system, and environmental factors. Estrogens, X chromosomal immune gene overdosage, and the presence of fetal tissue in the maternal circulation could all serve as predictors of autoimmunity in females. Health Conditions Health News: Latest News from Health Care, Mental Health, Weight Loss, Disease, Nutrition, Healthcare
