Objective : At present, mechanisms of hyaluronic acid (HA) synthesis are poorly understood. Specific antibodies against HA have not been produced, and the genetic study of HA production has not been conducted. The purpose was to understand HA production and deposition in the synovium of patients with rheumatoid arthritis (RA) exhibiting different degrees of inflammation.
Materials and methods : Each patient meeting the criteria of RA (American College of Rheumatology, ACR, 1987) was classified into 4 histological stages according to the degree of synovial inflammation ; A : early, B : moderate, C : active, and D : fibrotic stages. Synovia from 28 patients with RA were examined and as controls non inflamed and osteoarthritic synovia were studied. We investigated the distribution of HA by demonstrating a hyaluronic acid binding protein (HABP) histochemically, and the localization of HA producing cells was demonstrated by uridine diphosphoglucose dehydrogenase (UDPGD) activity using a technique described by Mehdizadeh (1991) . UDPGD is a key enzyme in the synthesis of proteoglycans including HA. The results were analyzed by a new quantitative technique using an image processor for analytical pathology (IPAP ; Sumitomo, Osaka) . Positive areas of HABP reaction, the number of UDPGD positive cells and the density of color developed by UDPGD activity, were measured with the IPAP system. HABP and the UDPGD activity were demonstrated by double staining.
Results : HA was highly concentrated in the superficial lining layer of synovia. The extent of HABP positive area, the number and optimal density of UDPGD positive cells, measured by IPAP, were highest in A (early) type synovia, (A>B>C>D) .When double staining was applied to synovial sections HABP positive area and UDPGD activating area overlapped.
Conclusion : Results indicate that HA distribution and UDPGD activity are affected by synovial inflammation. HA distribution and production normally decreases by inflammation.