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Sex Bias in Systemic Lupus Erythematosus and Sjögren’s Syndrome

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Women's Health in Autoimmune Diseases

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations in both clinical and immunological domains. Sjögren’s syndrome is another rheumatic, inflammatory autoimmune disease that is related to SLE at the level of clinical and serological manifestations as well as underlying pathophysiological mechanisms. For both diseases there are clearly genetic and environmental contributions to the risk of disease, but the etiology is largely undefined. Both SLE and Sjögren’s syndrome predominately affect women compared to men at a ratio of at least 10:1. The mechanism by which female-bias is mediated has not been fully elucidated. Sex steroids, estrogens and androgens, do not differ between SLE patients and controls with another chronic disease. Elevated levels of prolactin are found in the sera of some women with either SLE or Sjögren’s syndrome, but a cause and effect relationship is not established. The transcription factor vestigial-like family member 3 (VGLL3) may regulate sex-biased gene expression in a way that promotes autoimmunity. The X chromosome aneuploidies 47,XXY and 47,XXX are found in excess among men and women, respectively, with SLE or Sjögren’s syndrome. X chromosome genes that escape X inactivation, such as TLR7 and CXorf21, may mediate the X chromosome dose effect found in these diseases through effects of TLR7 signaling. Other X chromosome abnormalities including acquired X monosomy and skewed inactivation have not been found in SLE. The theory that genes escaping from X inactivation leads to increased intracellular protein concentration and subsequently to autoimmunity is untested. Thus, relatively new research has identified pathways other than sex hormones for female sex bias in these diseases. There may in fact be more than one mechanism by which autoimmune disease affects mostly women.

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Authors and Affiliations

  1. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    R. Hal Scofield & Valerie M. Harris

  2. Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    R. Hal Scofield & Valerie M. Harris

  3. Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    R. Hal Scofield & Valerie M. Harris

  4. Medical and Research Services, US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

    R. Hal Scofield & Valerie M. Harris

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  1. R. Hal Scofield
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  2. Valerie M. Harris
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Correspondence to R. Hal Scofield .

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  1. Department of Internal Medicine, PGIMER, Chandigarh, India

    Shefali Khanna Sharma

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Scofield, R.H., Harris, V.M. (2020). Sex Bias in Systemic Lupus Erythematosus and Sjögren’s Syndrome. In: Sharma, S. (eds) Women's Health in Autoimmune Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-15-0114-2_3

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