Study of the role of CD40 / CD40-L interaction in the pathogenesis of rheumatoid arthritis [RA]

CD40/CD40 ligand [CD4O/CD4O-L] interaction has pleiotropic effects in a variety of cells and biological processes including immune response. Within the immune system, these molecules represent a critical link between its humoral and cellular arms. Numerous autoimmune diseases are associated with CD40/CD40-L interaction. CD40 is a cell surface receptor that belongs to the tumor necrosis factor-receptor [TNF-R] family, and that was first identified and functionally characterized on B- lymphocytes. CD40 ligand [CD40-L] or [CD154], a member of the TNF superfamily, is a cell membrane molecule expressed on activated CD4+ T-lymphocytes. Therefore, it is now thought that CD40/CD40-L interactions play a more important role in autoimmune disease regulation. The aim of the present work was to measure the level of surface expression of CD40-L and CD40 on PB lymphocytes of rheumatoid arthritis [RA] patients and to correlate it with clinical and laboratory data and with disease activity. To achieve this goal, 30 patients with RA [Group I] who were further subdivided into group IA [15 patients with active RA] and group IB [15 patients with inactive RA], in addition to 20 healthy control volunteers [group II] were studied. All studied groups were subjected to routine laboratory investigations including, complete blood count [CBC], ESR, C-reactive protein [CRP], rheumatoid factor [RF] measured by latex test and by Rose-Waaler test. Surface CD40-L and CD40 expression on lymphocytes was measured by flowcytometry on peripheral blood [PB] of all studied groups. Statistical analysis of the results of the present study showed that surface expression of CD40-L on PB T-lymphocytes was significantly higher in RA compared to the control group. Among RA patients surface expression of CD40-L was significantly higher in active RA patients compared to inactive patients. As regards CD40 expression on PB, no statistical significance was observed among the studied groups. Therefore increased expression of CD40-L on PB T-lymphocytes could be regarded as a marker of disease activity in RA patients and to drive the activation of autoreactive beta-lymphocytes in the disease. These findings are particularly useful for clarifying the pathogenic process in RA patients and for developing a therapeutic approach that blocks pathogenic cytokine and antibody production

Lymphocyte apoptosis and proliferation related gene products in childhood acute lymphoblastic leukemia

The aim of the study is to characterize markers of apoptosis in children with ALL in relation to treatment outcome of the disease. The study was performed on 34 children with ALL and 60 healthy children as a control group. Apoptosis was assessed by cell morphology; DNA fragmentation; ELISA and RT-PCR for CD95, CD95L, BcL2 and NF-KB; and flowcytometry for CD95, CD40, CD49d, and CD11a. Apoptosis was significantly lower in cases than controls. Apoptosis detected by CD95 ligand was significantly lower in cases with no remission after treatment than those with remission. Antiapoptotic factors: CD40, BcL2, and NF-KB were all found to be higher in cases than controls and in cases with no remission than those with remission, CD49d was significantly lower in cases than controls, and significantly lower in cases with no remission. CD11a levels were not different among various groups. Delayed apoptosis of ALL cells is genetically controlled either directly or indirectly by a network of oncogenes and tumor suppressor genes. CD40 appeared to stimulate both T and lineage and is considered the most potent influencer and predictor to resistance to therapy. Inhibitors for the activity of CD40, 8c/2 and NF-kB as well as stimulants to CD95 could have a potential therapeutic benefit