Recipients of the Rheumatoid Arthritis Awards
Vyacheslav Adarichev, Ph.D.
Rush-Presbyterian-St. Luke's Medical Center, Chicago
2003 Sontag Foundation Fellowship of the Arthritis National Research Foundation
Grant Award: $50,000
-- Dr. Vyacheslav A. Adarichev
About Dr. Adarichev's Research:
Gender Effect on Arthritis Phenotypes in a Murine Model of Rheumatoid Arthritis
Rheumatoid Arthritis, the name for inflammation of a joint with involvement of the immune system, is one of the most frequent diseases affecting approximately 1% of the human population. Why and how the disease starts remains unclear. Rheumatoid arthritis is a systemic disease and eventually affects not only joints, but also other organs such as kidneys, lungs and heart. One of the intriguing disease features is that women are considerably more often (~3 times) affected with rheumatoid arthritis than men.
Studies at the very early stages of arthritis in human patients are a difficult task, particularly when symptoms are unclear or even absent. Animal models for the disease put the study of arthritis under the control of investigators. Arthritis can be induced in certain mouse strains with the injection of one of the major cartilage components named proteoglycan. Proteoglycan-induced arthritis is a mouse model for human disease which resembles rheumatoid arthritis both by clinical symptoms and genetics. One of the most valuable components of this model is that female animals are more susceptible than males, as in rheumatoid arthritis patients. This may be a critical issue as genetic risk factors are often different in males and females.
Mouse chromosome 15 seems to be a critical place in the genome, because it carries two independent genetic loci: the first locus controls arthritis but only in males, and the second locus activity is restricted primarily to females. Interestingly, genetic backgrounds of males and females are different by only a single chromosome, chromosome Y, which also has a clear impact on arthritis development.
Accordingly, to investigate the immunological and genetic mechanisms and effects of gender on arthritis, we propose putting together arthritis-controlling loci of chromosomes 15 and Y in different combinations, and look at their separate and cooperative effects upon the clinical and immunological features of arthritis. We anticipate describing and understanding the genetic mechanism of the locus-locus (chromosome 15 - chromosome Y) interaction in the development of proteoglycan-induced arthritis. This information can be adopted for, and will accelerate, corresponding human studies. Identification of arthritis genes on chromosomes 15 and Y will benefit the early diagnosis of arthritis in human patients, and this knowledge will further serve as a background for the development of therapeutic approaches for rheumatoid arthritis.
