Expression of cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4; CD152] on peripheral blood T lymphocytes in systemic lupus erythematosus children

Background: CTLA-4 [CD152] encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4/B7 is the most important costimulation-signaling pathway that regulates T cell responses and plays a critical role in maintenance and breakdown of selftolerance, and hence in susceptibility to autoimmune diseases

Objective: The aim of this study was to investigate and evaluate the expression of CTLA-4 on peripheral blood T-lymphocytes [PBTL] in children with systemic lupus erythematosus [SLE] in relation to clinical features; disease activity and severity

Methods: From December 2006 to August 2007, 32 pediatric patients [30 girls, 2 boys] fulfilled at least four of the 1997 revised criteria for the classification of SLE were enrolled in this study. Expression of CTLA-4 on freshly isolated PBTL was assayed by flow cytometry in all SLE patients during activity and remission in addition to 32 age- and sex-matched children serving as controls. Results were expressed as percentage of PBTL cells expressing surface CTLA-4 molecule in comparison to isotype-matched controls. CTLA-4+PBTL% were correlated with some SLE disease activity and severity variables

Results: CTLA-4 expression on freshly isolated PBTL was significantly higher in SLE patients during disease activity [median = 12; mean +/- SD = 10.45 +/- 8.3%] than controls [median = 4; mean +/- SD = 3.34 +/- 3.1%; p < 0.0001]. The patients' values were statistically comparable during quiescence [median = 14; mean +/- SD = 15.02 +/- 7.1%; p > 0.05] and activity. Among SLE patients, the median and mean +/- SD of CTLA-4+PBTL % of children with lupus nephritis was significantly higher than those without nephritis [15; 13.56 +/- 10.4% versus 10; 9.51 +/- 9.1%; p < 0.01]. CTLA-4 expression could be related to lupus severity but there was no correlation with disease activity. A positive correlation could be elicited between CTLA-4+PBTL% during lupus activity and the corresponding values during remission. CTLA-4+PBTL% correlated positively with the anti-dsDNA autoantibodies titers, serum creatinine, and 24 hours urinary protein excretion. On the other side, the percentages correlated inversely with the estimated creatinine clearance and serum C3 and C4 levels. CTLA-4 expression did not vary according to therapy

Conclusion: CTLA-4 surface expression on PBTL in SLE children was up regulated irrespective of lupus activity. The over expression was related to lupus severity and might have a significant role in the pathogenesis of lupus nephritis and cerebritis

Apolipoprotein E alleles in relation to serum lipids, lipoproteins and apolipoproteins in infants of diabetic mothers

Objectives: To determine whether infants of diabetic mothers have altered lipoprotein metabolism, whether these alterations persist or regress after one month of life and whether these alterations are genetically determined through Apolipoprotein E genotypes

Methods: The present study was performed in Ain Shams University, Neonatal Intensive Care Unit Children’s Hospital, and the follow up was done in the Newborn Clinic in the period from March 2002 to March 2003. The subjects were classified into the following groups: Group I: included 81 newborns of diabetic mothers [gestational or pregestational], 40 females and 41 males. Group II: included 76 full term healthy newborns to healthy mothers, 43 males and 33 females. They were subjected to: full history taking, thorough clinical examination, cord Serum lipid profiles [total cholesterol, triglyceride, HDL-c, LDL-c, Serum ApoA1, and ApoB100] serum glucose level, and serum insulin level for IDM. Follow up of only 33 newborns of group I and 23 newborns of group II after I month for repeating lipid profiles. ApoE genotyping by PCR was performed for 20 hyperlipidemic newborns of diabetic mothers [those with more than 2 SD increase in lipid profiles in the follow up samples after one month]

Results: There was a significantly higher cord blood lipids, lipoproteins and apolipoproteins concentrations in the IDM group compared to the control group. Both groups whether IDM and control group showed significant rise in lipid, lipoproteins and apolipoproteins levels at one month of life compared to their cord blood levels. But still there were significant higher levels in IDM group than the control group. Comparison between infants of gestational diabetic mothers and those of initially diabetic mothers as regard their lipid profiles at birth and at day 30 of life showed non significant difference. The frequency prevalence of Apo E alleles E2, E3 and E4 were 0, 75 and 25% respectively with Apo E 3 being the commonest allele followed by E4. No significant difference was detected as regards allele frequencies between the studied IDM. No significant difference was detected between IDMs with Apo E 4/3 genotype and those with Apo E 3/3 genotype as regard their lipid profiles whether at birth or after one month of life

Conclusion: IDM had altered lipid metabolism at birth, some of which persisted after one month and might play a role in the pathogenesis of diabetes and atherosclerosis in adulthood, however, these changes could not be related to Apo E genotyping as lipid metabolism is influenced by variety of environmental and physical factors

Recommendations: Longitudinal studies with prolonged follow up of lipid profile in IDM are needed to determine whether hyperlipidemia persists or disappears later in life

Serum arginine and glutamine concentrations in neonates with necrotizing enterocolitis

Objectives: TO determine if glutamine and arginine, which are essential for Intestinal integrity, are deficient in infants developing necrotizing enterocolitis [NFC]

Methods: This study was conducted on 44 preterm newborns [-3d 35 weeks of gestation]. The patients group comprised 17 infants who developed NEC between postnatal days 3 and 11. According to Bell’s staging criteria, the patients were subdivided into 3 subgroups: 6 at stage I [suggestive], 8 at stage II [definitive], 3 at stage III [advanced]. The remaining 27 newborns served as a control group and consisted of neonates without detectable signs of NEC by day ll. Serum arginine [ARG] and glutamine [GLN] levels were measured by high pressure liquid chromatography [HPLC] of samples obtained on postnatal days 3 and 11

Results: Significantly lower levels of serum ARG and GLN were encountered on day 11 compared with day 3 in the patient group [P<0.05].There was no significant difference in both amino acids levels between the NEC group compared with the control group. Serum ARG and GLN correlated positively with gestational age in the control group [rho=0.48 P<0.05 for ARG and 0.41 P<0.05 for GLN]. There was a significant positive correlation between ARG and GLN serum levels [rho=O.772, 0.645, 0.743 P<0.05 for ARG and rho=0.642, 0.772, 0.605 P<0.05 for GLN]. The results revealed also that ARG and GLN significantly decreased on day 11 compared to day 3 at stage II and but was statistically comparable at stage I and did not reach significance at stage III

Conclusion: In conclusion, the diminished concentration of serum ARG and GLN in preterms with NBC may play an important role in the pathogenesis of the disease. Recommendations: Further studies on the efficacy and safety of higher doses of parenteral ARG and GLN are needed to be studied in premature infants. A trial investigating the benefits and risks of selective amino acid supplementation in the prevention of NBC is needed