Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis

Background: Animal studies have indicated that 5-HT2(A) receptors could play a role in arthritic diseases. Objective: To analyse the binding properties of 5-HT2(A) receptors in patients with rheumatoid arthritis. Methods: Using a radioactive binding assay, 43 patients with rheumatoid arthritis were compared with 49 sex and age matched controls for density and affinity (measured as B-max and K-d) of 5-HT2(A) serotonin receptors. Genotyping, using polymerase chain reaction, was undertaken to exclude the possibility that differences in the genetic polymorphism T102C for the 5-HT2(A) receptor determine differences in receptor density. Results: Mean of B-max of 5-HT2(A) receptors in rheumatoid patients was significantly lower than in controls, at 45.3 v 57.4 fmol/mg protein (p = 0.004), but there was no significant difference in K-d. The T102C receptor polymorphism genotypes showed a skewed distribution between the two groups. Even when adjusted for this, there was a significant difference in B-max between the groups. Conclusions: The density of 5-HT2(A) serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease.