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Why Are Autoimmune Diseases More Common in Women than Men?

No matter if it’s rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or multiple sclerosis (MS): most autoimmune diseases affect women significantly more often than men. It is possible that this could be at least partially explained by the occurrence of age-associated B cells (ABCs), as described in an article recently published in Blood, the journal of the American Society of Hematology.

Why autoimmune diseases are more common in women than men is actually far from fully understood. In previous years, scientists researching the cause primarily focused on the differences in hormone levels between men and women. The genetic differences between men and women are also clearly one of the reasons for the significantly higher incidence of autoimmune diseases in those of the female sex.

Aside from hormones and genetic predisposition, another possible cause has now been found by Anatoly V. Rubtsov, Kira Rubtsova, Aryeh Fischer, Richard T. Meehan, Joann Z. Gillis, John W. Kappler, and Philippa Marrack. In a current article in Blood, these scientists describe a special form of B cells known as CD11c+ B cells. These cells express a special integrin, the CD11c molecule, on their surface. In animal experiments with mice, the number of these special B cells increases with age – but only in females.

Age-associated B cells also in female RA patients

The researchers working with Anatoly V. Rubstov have also found such age-associated B cells, ABCs, in female patients with autoimmune diseases (Rubtsov et al., Blood 2011 online). The scientists have observed that the number of these B cells also increases with age in women with rheumatoid arthritis (RA). It is thus possible that Rubstov’s research group has now found another explanation in addition to hormonal risk factors and the sex-linked chromosomes for why women suffer from autoimmune diseases more often than men.

And there is another factor involved with ABCs: The activation of these special B cells is stimulated by means of toll-like receptor 7, TLR-7. The gene for TLR7 is located on the X chromosome. Women thus have two copies of the TLR-7 gene in their genome – which brings genetics into play with regard to the age-associated B cells as well.

A very nice overview of this topic can be found in the review article Why Are Women Predisposed to Autoimmune Rheumatic Diseases? by Jacqueline E. Oliver and Alan J. Silman, which appeared in the journal Arthritis Research & Therapy in October 2009. (Please note: This paper covers information current in 2009, the more recent work by Rubstov et. al, is thus naturally not included!) This article is available to anyone in the BioMed Central – reading tip!

Author of this article:  Tobias Stolzenberg

Literature:

Oliver JE, Silman AJ. Why are women predisposed to autoimmune rheumatic diseases? Review. Arthritis Res Ther. 2009;11(5):252. – link opens the free full-text article

Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ, Kappler JW, Marrack. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c+ B-cell population is important for the development of autoimmunity. Blood. 2011 Aug 4;118(5):1305-15. Epub 2011 May 4. – doi:10.1182/blood-2011-01-331462 – link opens the abstract

 

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