Correlation of apoptotic indices with clinical criteria in rheumatoid arthritis and osteoarthritis

Recent studies clarified the role of apoptosis in the pathophysiology of autoimmune diseases. To further clarify this point, the apoptotic indices, soluble Fas [s-Fas], lipid peroxides [LPER] representing oxygen free radical activity, nitric oxide [NO], interleukin-1B [IL-1B], cathepsin L and B were determined in the sera of patients with rheumatoid arthritis [RA] and osteoarthritis [OA] in comparison with controls. The study included 18 patients with RA, 32 patients with OA together with 10 age and sex matched healthy persons representing a control group. Serum from each participant was used for determination of apoptotic indices. The study revealed significantly increased levels of s-Fas, LPER, NO, IL-1B, cathepsin B and L in patients with RA and OA as compared with controls. Moreover, the levels were significantly higher in RA as compared with OA. The levels of these indices correlated with disease severity being higher though insignificantly so in cases associated with fever and advanced X-ray grading. Moreover, significant positive correlations were observed between articular index and LPER [r = 0.58 and p < 0.05] in RA and between ESR and NO [r = 0.39 and p < 0.05], IL-1B [r = 0.41 and p < 0.05], cathepsin B [r = 0.41 and p < 0.05] and cathepsin L [r = 0.38 and p < 0.05] in OA. Also, significant positive correlations were observed between IL-1B levels and NO, cathepsin B and cathepsin L in either RA or OA, clarifying the important role of IL-1B in the induction of NO cathepsin B and L synthesis. In conclusion, the present study further clarified the role of Fas dependent apoptotic pathway in RA and OA. Thus, the supply of Fas ligand could be a novel therapeutic technique in the future. Moreover, antisense oligonucleotides against IL-1B could also be used to control the deleterious effects of cytokine network in RA and OA

Correlation of indices of activity of inflammatory joint disease with nucleoside triphosphate pyrophosphohydrolase

Osteoarthritis [OA] and rheumatoid arthritis [RA] are the most common diseases affecting the joints. Up till now, good understanding of their pathology and a specific diagnostic laboratory abnormality is required. In recent years the role of the enzyme nucleoside triphosphate pyrophosphohydrolase [NTPPase] has been clarified. In the present study, the activity levels of this enzyme in the serum, plasma and urine were determined in 32 patients with bilateral knee OA as well as 18 patients with RA together with 10 healthy subjects comparable in age to patients representing a control group. Meanwhile, serum hyaluronan and sialic acid levels were determined in all participants. The study revealed significantly increased levels of NTPPase in the sera, plasma and urine of patients with knee OA and RA as compared to controls. The activity levels were significantly higher in the sera, plasma and urine of patients with knee OA as compared to RA. No differences in the enzymatic activity could be observed between plasma and serum enzyme activity, ruling out the participation of platelets as a source of this enzyme. The increased activity levels in OA and RA could originate from an accelerated proteolysis associated with inflammatory arthritis, accompanied with enhanced lymphatic clearance from the affected joints with release of soluble degradation products into the blood. Meanwhile, the significantly higher enzymatic activity levels in OA as compared with RA could indicate different inflammatory mechanisms. Serum levels of hyaluronan and sialic acid were significantly increased in either OA or Ra as compared with controls but the levels were significantly higher in RA when compared with OA. The levels of all indices studied increased with the duration of knee OA and RA, but the differences were significant only in OA. The levels also reflected X-ray grading in either OA or RA. Significant positive correlations existed between serum and NTPPase with hyaluronic acid and sialic acid. In conclusion, the present study further clarified the differences in pathological nature between OA and RA as evidenced by significantly higher NTPPase in OA compared with RA but significantly increased hyaluronan and sialic acid in RA as compared with OA. Therefore, therapeutic interventions are totally different in the 2 conditions. The severity of RA can be predicted better from hyaluronan and sialic acid while OA from NTPPase