Autoimmunity

One of the pressing questions in Immunology is why autoimmune and infectious diseases prefer one gender over another. Most autoimmune diseases are prevalent in females, and tables of disease prevalence in the sexes are routinely given in medicine. Many autoimmune conditions are predominant in women. Diseases like Sjogren syndrome, rheumatoid arthritis, and multiple sclerosis are a few conditions found frequently in women. Perhaps the most studied illness concerning sex and gender is Systemic Lupus Erythematosus, which is often called the prototypic autoimmune disease. However, a sex and gender skew can be found in many infectious diseases (such as Covid19) as well.

Autoimmune diseases, with their intricate etiology, are believed to be triggered by many factors. These include genetic predisposition, epigenetic regulation (mRNA, DNA methylation, and histone modifications), antigenic mimicry in particular infections, and potentially other mechanisms that are yet to be fully understood.

Hormonal metabolism has been studied in various autoimmune diseases. Early animal work showed that high concentrations of estrogen enhance autoimmune disorders, whereas androgens have the opposite effect and seem to downregulate the immune response. A large body of murine experimentation in genetically SLE-prone mice demonstrated that ovariectomy could ameliorate disease, whereas exacerbation would occur with estrogen enhancement in males.

Studies of various conditions in women, like endometriosis, where estrogen levels can be very high, promote the presence of autoantibodies. Other normal conditions like pregnancy can also produce a variety of non-harmful antibodies that abate when gestation is over.

While the effects of sex steroids like estrogen, progesterone, and androgens on the immune response have been extensively studied, there are still some mysteries to unravel. For instance, other hormones like prolactin have been found to enhance the immune response in patients with pituitary adenomas. Still, the reasons behind this phenomenon remain unclear, presenting an exciting avenue for further research.

Recently, genomic pathways that were always thought to play a role in the skew of autoimmune disease because of observations in Klinefelter disease (XXY males) who are 14-fold more likely to get an autoimmune disease and other conditions where the X chromosome as in Turner syndrome played a seminal role are shown to be extremely important. It can indeed be said that genetic and epigenetic factors are responsible for sexual dimorphism in autoimmune diseases. In prepubertal females, when sex hormone levels are low, females develop diseases over their age-matched male counterparts. X inactivation during embryogenesis is critical to gene expression in females, and the role of the X chromosome in autoimmunity is now solid and supported by the Xist studies recently reported.

The X chromosome encodes many genes that could be associated with disease: CD40L, CXCR3, OGT, FOXP3, TLR7, TLR8, IL2RG, BTK, and IL9R. Micro RNAs, encoded on sex chromosomes, may contribute to sex differences in disease because they are enriched on the X chromosome.

The studies of gender and sex in autoimmune disease are ongoing and extremely important to our understanding of pathogenesis and possibly methods of treatment.

This article collection will explore the genetic, epigenetic, hormonal, and anatomical differences between males and females that affect the immune response and contribute to differing rates of autoimmune disease. We welcome the submission of Research Articles, Review Articles, Brief Reports, and Methods.

Topics of interest include, but are not limited to:

• How epigenetic factors, such as diet, environment, and age, might affect a dimorphic immune response.
• The effects of estrogen, testosterone, and progesterone on the dimorphic immune responses.
• Studies of oral contraceptives on both the onset and course of the autoimmune diseases.
• Gonadal pathologies in women like endometriosis, polycystic ovarian disease, or hypogonadism in men (from trauma or disease) and its effects on dimorphic presentation.
• The specific effects of pregnancy on the onset and course of autoimmunity and autoimmune disease effects as a result of pregnancy.
• The role of the pituitary and hyperprolactinemia on the presentation of autoimmune disease.
• The role of sex chromosomes on immune function (Klinefelter and Turner syndrome).
• Micro RNAs and Xist chromosomal inactivation as reasons for dimorphism in autoimmune disease.

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Submission Instructions:

All manuscripts submitted to this Article Collection will undergo full peer-review; the Guest Advisor will not be handling submitted articles. Please review the journal’s aims and scope and author instructions prior to submission.

Please submit your manuscript through Taylor & Francis's Submission Portal.

During the first step of the submission process (under the "Manuscript Details" heading), you will find the question "Are you submitting your paper for a specific special issue or article collection?" Click the radio button for "Yes".

Next, you will be prompted to select the "Special Issue or Article Collection name" from the dropdown menu. Choose "The Intriguing Interplay of Sex and Gender in Autoimmunity and Immunity" from the list. This will ensure that your manuscript is considered for inclusion.

The manuscript submission deadline is 1 November 2024.

If you have any questions about this Article Collection, please contact Krista Thom at [email protected].

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Guest Advisor:

Robert G. Lahita, MD, Ph.D, is a rheumatologist/immunologist who has spent most of his career studying the dimorphic sexual response in autoimmune disease. Specifically, he has studied the reason for the gender skew towards females of many species. Dr. Lahita trained with Henry G. Kunkel (immunology), Jack Fishman, and Leon Bradlow (steroid biochemistry) at Rockefeller University in New York City. He is currently the Director of the Institute for Autoimmune and Rheumatic Disease at St. Joseph Health in New Jersey.

Disclosure Statement: Dr. Lahita discloses no conflict of interest.

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