Apoptosis regulator proteins: basis for the development of innovation strategies for the treatment of rheumatoid arthritis in patients of different age.

Apoptosis markers (p53, PUMA, p21, and Mdm2) were studied in patients with rheumatoid arthritis at the early and late stages of disease on bone marrow smears and frozen sections of the articular synovial membrane. The target molecules were found in all patients. The early stage was characterized by maximum expression of antiapoptotic (Mdm2) molecule and the minimum expression of proapoptotic molecules (p53, PUMA, and p21). The proapoptotic proteins predominated in patients with the late stage of rheumatoid arthritis, while the antiapoptotic factor (Mdm2) was depressed significantly. These data suggested total suppression of apoptosis at the early stage of rheumatoid arthritis and recommended the Mdm2 molecule as a prospective target for the development of new drugs.