Lack of association of CTLA-4 + 49 A/G polymorphism with predisposition to type 1 diabetes in a cohort of Egyptian families

Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. Apart from the Major Histocompatibility locus which is the main contributor to risk susceptibility, more than 40 loci are recognized. One among these is the CTLA-4, however data from the literature are controversial. The aim of our study was to investigate the role of CTLA4 49 A/G as a risk susceptibility factor for the development of type 1 diabetes in a cohort of Egyptian families. This is a case control study including 88 Egyptian families with one or more index cases [< 18 years]. The control group comprised 369 healthy unrelated subjects with no family history of diabetes or autoimmune disease. Using PCR-RFLP methodology, CTLA4 49 A/G was analyzed in 738 samples representing 88 families [88 patients, 125 siblings and 156 parents] and 369 control. The age of onset was 6 days-12.5 years with a mean of 5.3 +/- 3.6 and a median of 5 years. The mode of presentation was classic symptoms in 51 and diabetic ketoacidosis in 37 cases. Twenty-two cases had a history of viral infection or exanthematous disease and four had associated autoimmune diseases. No significant differences were encountered between the different groups with regard to CTLA4 +49 A/G genotype or allele frequencies. Neither was there a relation between the various genotypes and age of onset or the mode of presentation. CTLA4 49 A/G polymorphism was not recognized as a risk susceptibility factor in our cohort. This may be attributed to the low co-incidence of autoimmune diseases. Up to our best knowledge, this is the first study involving families. We recommend that all studies performed on risk susceptibility to type 1 diabetes should include proper investigation for other autoimmune diseases to exclude their confounding effect on data analysis

Anti-Nucleosome antibodies as a diagnostic tool in systemic lupus erythematosus and marker of lupus nephritis

To evaluate the prevalence of anti-nucleosome antibodies [anti-NCS Abs] in systemic lupus erythematosus [SLE], their role in diagnosis, disease activity and lupus nephritis [LN]. The study was conducted on 23 SLE female patients. They were divided into two groups according to the presence or absence of LN. Ten apparently healthy individuals served as a control group. Clinical assessment was done to all patients especially for renal affection. Disease activity was scored with SLEDAI. Anti-NCS and anti-dsDNA antibodies were measured with ELISA. Renal biopsy was performed for patients with LN. The prevalence of anti-NCS Abs was [78.3%] and anti-dsDNA Abs was [56.5%] in SLE. Seventeen patients presented with LN and 6patients without. Among these patients, the prevalence of anti-NCS Abs and anti-dsDNA Abs were [88%-64.7%] and [50%-33.3%] respectively. Anti-NCS Abs were found to be positive in 21.7% of SLE patients lacking anti-dsDNA Abs. The mean anti-NCS and anti-dsDNA Abs tiler in SLE was 250.60 +/- 207.00 and 443.3 +/- 714.3 respectively, showing a highly significant increase compared with healthy controls [12.3 +/- 4.54 and 31.0 +/- 20.11] [p<0.001]. Moreover, in LN and those without LN, the mean anti-NCS Abs showed a highly significant increase [331.41 +/- 179. 73 and 21.67 +/- 8.36] [p<0.001], while there was a significant increase in the mean of anti-ds DNA Abs [574.71 +/- 794.07 and 71.17 +/- 46.99] [p<0.05] respectively. The sensitivity and specificity of anti-NCS Abs in SLE were 82.6% and 100% and in LN were 88.2% and 100% respectively. Anti-NCS Abs showed a positive significant correlation with ESR [r=0.900], SLEDAI [r=0.761] and anti-dsDNA Abs [r=0.681] in LN, but showed a negative significant correlation with disease duration [r=-0.511] and C4 [r=-0.650] in patients without LN. In LN 7 patients hadproliferative glomerular lesion [WHO class III], 6 patients class IV and 4 patients class II on renal biopsy. They were associated with a statistically significant proteinuria, anti-ds DNA and anti-NCS especially in classes II and IV, Anti-NCS Abs could be a useful parameter for diagnosis and assessment of disease activity and LN in SLE, It seems to be a more sensitive marker of SLE than anti-ds DNA especially in patients who are anti-dsDNA antibody negative