Role of tumor necrosis factor-alpha converting enzyme in production of TNF-alpha by osteoarthritic articular chondrocytes

The study was conducted to find out the expression and function of TNF-alpha converting enzyme [TACE] in the articular cartilage of osteoarthritis [OA] patients. The cartilage was examined to investigate the post-translational regulation of TNF- alpha production by TACE in those OA patients. RT-PCR for TACE and TNF- alpha mRNA were performed on articular cartilages from 38 OA patients and 20 healthy controls. The function of TACE in OA affected cartilages was investigated by using TACE inhibitor, which was added in different concentrations to OA cartilage organ cultures and the released cytokines and soluble cytokine receptor in culture supernants were measured with ELISA. Expression of TACE and TNF- alpha mRNA by RT-PCR was detected in all OA affected cartilages, but not in normal cartilages. TACE inhibitor in high concentrations significantly reduced the release of TNF- alpha, sTNF-RII and IL-8 from chondrocytes from OA patients and normal peripheral blood monocytes from healthy controls. TACE is an important regulator of the secretion of TNF- alpha from articular chondrocytes of OA patients

Changes in serum levels of soluble interleukin-2 receptor and fas-ligand expression in relation to disease activity of systemic lupus erythematosus

Serum soluble IL-2 receptors [sIL2R] levels and Fas-ligand [Fas-L] expression on peripheral blood mononuclear cells [PBMC] were determined in patients with Systemic Lupus Erythematosus [SLE] to assess whether there was any relationship between them and disease activity. Enzyme Linked Immunosorbant assay [ELISA] technique was done on serum samples collected from 36 SLE patients and 25 healthy controls for determination of sIL2R level. RT-PCR was done also on PBMC samples collected from the same patients and controls for detection ofFas-L mRNA. We found significant increase of sIL2R in the SLE group [327.6 +/- 73.5 pg/ml] compared to healthy controls [119.7 _ 12.6 pg/ml] [p<0.001]. Levels of sIL2R were found to correlate significantly with clinical manifestation and serological markers of active SLE: fatigue [p<0.05], renal involvement [p<0.01], pulmonary involvement [p<0.05], high levels ofanti-ds DNA antibody [p<0.001] and high C3 level [p<0.0001]. Fas-L mRNA was expressed in PBMC from [88.9%] SLE patients and not detected in healthy controls. Fas-L positive SLE patients correlate significantly with clinical manifestation and serological markers of active SLE: fatigue [p<0.0001], rash [p<0.05], renal affection [p<0.001], high levels ofanti-ds DNA antibody [p<0.0001] and high C3 level [p<0.0001]. Levels ofsIL2R and Fas-L expression correlate significantly with disease activity [p<0.001, 0.001, 0.05, 0.005, respectively]. these findings indicate that sIL2R represent a new early useful serological marker to monitor disease activity in SLE patients. Fas-L expression increased in SLE patients, this increasing was in parallel to disease activity, so it is used as late marker to monitor the severity of the disease

Epstein-Barr virus [EBV] and EBV antibodies in adolescent systemic lupus erythematosus

To assess whether the adolescent systemic lupus erythematosus [SLE] patients had a presumed primary or reactivated EBV antibodies response as evidence of an active EBV infection. The study was conducted on serum samples collected from 35 adolescent SLE patients and 26 apparently healthy controls. EBV serologic response, VGA, IgG and IgM, EBNA antibody and anti-EA were measured with Enzyme Linked Immunosorbent Assay [ELISA]. PCR was done on peripheral blood mononuclear cells [PBMC] and saliva samples from same patients and controls for detection of EBV DNA. In addition, immortalization assay was done on PBMC and saliva samples for detection of active EBV. EBV serologic responses VGA IgM and IgG, EBNA antibody and EA antibody were detected in a high statistically significant level in adolescent SLE patients than healthy controls [p<0.0001, 0.001, 0.005 and 0.0001 respectively]. The incidence of primary EBV infection and reactive EBV infection in adolescent SLE patients studied according to serologic responses were 60% and 40% respectively. EBV serologic responses in healthy controls were in very low detectable level and classified as an EBV past-infection. EBV genomic material was not found in PBMC or saliva of patients or controls. We only detected in a single row active EBV with immortalization assay in PBMC of reactivated one SLE patient. Serologic profiles were more likely a consequence of immune dysregulation secondary to SLE or its therapy rather than rampant infection with EBV

role of interleukin-16 in the immunopathogenesis of rheumatoid arthritis

We analyzed, interleukin-16 [IL-16], in relation to disease activity to characterize its biologic function in RA. Secreted IL-16 was measured with enzyme immunoassay in the sera from 30 RA patients and 30 apparently healthy controls as well as in synovial fluid [SF] from 16 RA patients and 15 patients with non-RA synovitis as controls. IL-16 expression in peripheral blood mononuclear cells [PBMC] was characterized with flow cytometric analysis after intracellular cytokine staining for IL-16. In synovial tissue specimens, both were done: immunohistochemistry for localization of IL-16, and histopathology, in which the tissue was scored semiquantitatively for synovial hyperplasia and cellular infiltration. IL-16 was detected at significantly higher levels in sera and SF of RA patients in comparison to apparently healthy controls and non-RA synovitis [p < 0.001 and p<0.0001 respectively]. Also, IL-16 was detected significantly higher in SF in comparison to sera in RA patients [p<0.001]. Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ cells expressed IL-16 protein. Also, immunohisto-chemistry revealed more CD4+ and less frequency of CD8+ cells in synovial infiltration. A significant correlation between IL-16 expression and local inflammatory activity could not be established [p>0.21] with microscopic analysis of the synovial cells infiltrate. In addition, no significant association was observed between serum, SF, and synovial tissue expression of IL -16 and clinical disease activity in RA [p>0. 61, p>0.5 and p> 0. 42 respectively]. IL-16 seems to play a regulatory rather than a proinflammatory role in the immunopathogenesis of RA