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

Pancreatic beta-cells function and anti-insulin antibodies in children with down syndrome

Down syndrome has been linked with many autoimmune disorders. Type 1 diabetes mellitus is more prevalent in Down syndrome. The autoimmune etiology of type 1 diabetes mellitus has been well documented after the discovery of insulin autoantibodies in newly diagnosed diabetics and in individuals at high risk for type 1 diabetes mellitus. The aim of this work was to assess pancreatic beta-cells function and presence of anti-insulin antibodies in children with Down syndrome for possibility of occurrence of pancreatic dysfunction before development of overt diabetes mellitus. The study was carried out on twenty Down syndrome children aged from 4 to 15 years, none of them had history of diabetes mellitus or other autoimmune disease. Ten age and sex matched apparently healthy children with normal karyotyping served as controls. All of them were subjected to full history taking and thorough clinical examination followed by assessment of anti-insulin antibodies with blood glucose and C-peptide levels at fasting state, 2 minutes, 30 minutes and an hour after intravenous infusion of glucose 10% [5 ml/kg body weight] as a challenge test. The results showed that two girls with Down's syndrome had anti-insulin antibodies levels above the cut- off point of anti-insulin antibodies 1> 10.09 u/ml]. The first one, aged 4 years, had fasting blood glucose level 124mg/dl then 140mg/dl one hour after infusion. Her fasting C- peptide level was 0.8ng/ml then 1.ing/ml after one hour of the intravenous glucose tolerance test. The second girl, aged 14 years, had fasting blood glucose 118mg/dl then 130mg/dl one hour after glucose infusion. Her fasting C-peptide was 0.9ng/ml then 1.7 after one hour of the intravenous glucose infusion. Female children had significantly higher blood glucose level at fasting state and one hour after glucose infusion. There was significant proportional correlation between anti-insulin antibodies and blood glucose level at lasting state, two minutes, half an hour and one hour after intravenous glucose infusion and significant inverse correlation were found between it and C-peptide levels at fasting state , two minutes and half an hour after the challenge test

Conclusions and Recommendations: tests to assess anti insulin antibodies should be included in Down syndrome children care and Follow up of Down syndrome children with positive anti insulin antibodies may be of value particularly when therapies become available to preserve beta cell mass. Early detection and consequently early treatment might reduce the burden and complications of diabetes in those children