RESEARCH - Sex differences and RA

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Medscape Rheumatology

From ARTHRITIS & RHEUMATISM Research News Alerts

Posted 01/23/2007

Sex Differences and Rheumatoid Arthritis

Characterized by chronic synovial tissue inflammation, increasing erosions

of cartilage and bone, and eventual destruction of joints, rheumatoid

arthritis (RA) is a complex and confounding autoimmune disease. It is

associated with a variety of genetic and environmental factors and known to

strike women about three times as frequently as men. A major obstacle to

investigating this clear sex bias has been the lack of a laboratory rat or

mouse that mimics human RA. Until now.

Researchers at the Mayo Clinic have produced a new breed of transgenic mice

with autoimmune responses similar to human RA patients and increased

incidence of the disease in females. Featured in the January 2007 issue of

Arthritis & Rheumatism

(http://www.interscience.wiley.com/journal/arthritis), this humanized mouse

model may be valuable for not only studying sex differences in RA, but also

for understanding why women are particularly vulnerable to autoimmunity and

for developing future therapeutic 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-induced arthritis

(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 rheumatoid

factors and anti-CCP autoantibodies strikingly similar to humans. These

included auto antibodies to type II collagen (CII), increased expression of

class II molecules T cells, and production of proinflammatory cytokines. In

addition, female mice developed arthritis at a higher rate than the male

mice, by a ratio greater than 3 to 1, and exhibited all the disease

hallmarks at higher levels.

Commenting on this study's implications for further understanding and future

treatment of RA, Maurizio Cutolo, M.D., a researcher with the Department of

Rheumatology, the University of Genoa, Italy, considers its potential to

shed light on the role of estrogen and androgen in the disease.

" Sex hormone balance is a crucial factor in the regulation of immune and

inflammatory responses, " Dr. Cutolo notes. " Modulation of this balance

should represent part of advanced biologic treatments for RA. Sharing the

sex hormone effects of the human disease, the new humanized mouse may

provide a better model with which to study the pathogenesis and treatment of

arthritis. "

http://www.medscape.com/viewarticle/550579

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