Varying expression of four genes sharing a common regulatory sequence may differentiate rheumatoid arthritis from ageing effects on the CD4(+) lymphocytes.

The CD28 gene is similarly down-regulated in CD4(+) lymphocytes from both healthy elderly people and patients with rheumatoid arthritis (RA) because of impaired protein-binding activity of the 'α' sequence in its promoter region. Other genes important for the CD4(+) cell function may share that sequence and may be similarly regulated and affected. We searched GenBank for possible 'α' homologues and then compared transcriptional activities of the respective genes in the CD4(+) cells of young and older healthy individuals and those with RA by real-time PCR. We show here that genes encoding one of the zinc finger proteins (ZNF334), the 'aging hormone' Klotho, the retinoid acid receptor β2 (RARβ2) and the T-cell adapter protein GRAP-2, contain sequences with various (exceeding 70%) degrees of homology to the 'α' sequence near their promoters. These genes are transcribed in human CD4(+) lymphocytes; the expressions of RARβ2, KLOTHO and ZNF334 are significantly decreased in a correlated manner in the cells of patients with RA compared with those of healthy individuals. In RA patients, the extremely reduced expression of ZNF334 does not depend on the individual's age, apparently constituting a disease-related phenomenon; whereas that of RARβ2 and KLOTHO occurs mostly in the cells of relatively younger patients, making them similar to the lymphocytes of healthy elderly in this aspect.