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Editorial
. 2024 Feb;44(2):203-209.
doi: 10.1007/s00296-023-05446-8. Epub 2023 Sep 16.

Sex bias in immune response: it is time to include the sex variable in studies of autoimmune rheumatic diseases

Lazaros I Sakkas  1   2 , Ian C Chikanza  3   4
Affiliations
Editorial

Sex bias in immune response: it is time to include the sex variable in studies of autoimmune rheumatic diseases

Lazaros I Sakkas et al. Rheumatol Int. 2024 Feb.

Abstract

Healthy females and males differ in their immune cell composition and function and females generally mount stronger immune response than males and are much more susceptible to autoimmune rheumatic diseases. Females differ from males in sex hormones, and X-chromosome genes. Sex hormones affect immune cells and responses, and may induce epigenetic DNA changes. The importance of X-chromosome genes is exemplified in men with the Klinefelter syndrome (47,XXY) who have an additional X-chromosome and develop systemic lupus erythematosus(SLE) as frequently as women. X-chromosome contains genes critical for the immune response, such as FOXP3, toll-like receptor(TLR)7, TLR8, CD40 Ligand, IL2RG, IL9R, BTK, and others. Whereas one X-chromosome in females is randomly inactivated early in embryonic development, around 25% of X-linked genes escape inactivation and result in more X-linked gene dosage in females. We use two key female-biased autoimmune rheumatic diseases, SLE and systemic sclerosis, to review differences in immune response, and clinical manifestations between females and males. The inclusion of sex variable in research will facilitate precision medicine and optimal patient outcome.

Keywords: Bias; Difference; Female; Male; Precision medicine systemic sclerosis; Sex; Systemic lupus erythematosus.

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