Health News
Sex Differences and Rheumatoid Arthritis
December 26th, 2006
New Lab Mouse from the Mayo Clinic Offers Promise for Studying Increased Risk of Autoimmune Inflammatory Diseases in Women.
Characterized by chronic synovial tissue inflammation, increasingerosions of cartilage and bone, and eventual destruction of joints, rheumatoidarthritis (RA) is a complex and confounding autoimmune disease. It is associatedwith a variety of genetic and environmental factors and known to strike womenabout three times as frequently as men. A major obstacle to investigatingthis clear sex bias has been the lack of a laboratory rat or mouse that mimicshuman RA. Until now.
Researchers at the Mayo Clinic have produced a new breed of transgenicmice with autoimmune responses similar to human RA patients and increasedincidence of the disease in females. Featured in the January 2007 issue of Arthritis & Rheumatism , this humanized mouse model may be valuablefor not only studying sex differences in RA, but also for understanding whywomen are particularly vulnerable to autoimmunity and for developing futuretherapeutic strategies.
For this novel experiment, mice were genetically modified with a well-established RA susceptibility, the allele HLA-DRB1*0401. This gene variant is linked to anti-cyclic citrullinated peptide (anti-CCP) autoantibodies, which precede the onset of RA. Collagen-inducedarthritis (CIA) in the mice was initiated by injection of type II collagen. These transgenic mice were then tested for incidence and severity of arthritic symptoms, as well as assessed for vulnerability to the disease by sex.
Of the transgenic mice that developed arthritis, all produced rheumatoidfactors and anti-CCP autoantibodies strikingly similar to humans. Theseincluded auto antibodies to type II collagen (CII), increased expression of classII molecules T cells, and production of proinflammatory cytokines. In addition, female mice developed arthritis at a higher rate than the malemice, by a ratio greater than 3 to 1, and exhibited all the disease hallmarksat higher levels.
Commenting on this study's implications for further understanding andfuture treatment of RA, Maurizio Cutolo, M.D., a researcher with the Departmentof Rheumatology, the University of Genoa, Italy, considers its potential toshed light on the role of estrogen and androgen in the disease. "Sex hormonebalance is a crucial factor in the regulation of immune and inflammatoryresponses," Dr. Cutolo notes. "Modulation of this balance should represent part ofadvanced biologic treatments for RA. Sharing the sex hormone effects of thehuman disease, the new humanized mouse may provide a better model with whichto study the pathogenesis and treatment of arthritis."
Article: "New Humanized HLA-DR4-Transgenic Mice That Mimic the Sex Bias of Rheumatoid Arthritis,"Veena Taneja, Marshall Behrens, AshutoshMangalam, Marie M. Griffiths, Harvinder S. Luthra, and Chella S. David, Arthritis& Rheumatism, January 2007; (DOI: 10.1002/art.22213).
Editorial: "Sex and Rheumatoid Arthritis: Mouse Model Versus Human Disease," Maurizio Cutolo, Arthritis & Rheumatism, January 2007;(DOI: 10.1002/art.22322).
SOURCE: John Wiley & Sons, Inc
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