HLA-DRB1 alleles in Egyptian children with systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is an autoimmune disease characterized by multisystem organ damage due to autoantibody production. Polymorphism in genes at the Major histocompatibility complex [MHC] region represents an important susceptibility factor for SLE, especially HLA-DRBI and HLA-DQB1. Moreover; it was noted that ethnicity has a significant role in both disease susceptibility and disease expression. This work was planned out to study HLA-DRBI alleles association with SLE susceptibility and clinical presentations in Egyptian children with juvenile onset SLE. HLA-DRBI allele typing was done using polymerase chain reaction-sequence-specific oligonucleotide probe for 65 juvenile SLE patients and compared to 150 healthy controls of the same ethnic group. P values were corrected for the number of the alleles tested [Pc]. HLADRB1 asterisk 15 allele was significantly increased in SLE children Vs controls [OR=3.44; 95%CI=1.51-7,83; P=0.004 and Pc=0.048]. No HLA-DRB1 allele was found to be statistically significantly associated with renal, musculoskeletal, cutaneous, hematologic, cardiac or neuropsychiatric manifestations in children with SLE [P>0.05]. Although HLADRB1 asterisk 15 [15g] allele may be a susceptibility allele in Egyptian children with juvenile SLE; however HLA-DRB1 alleles do not contribute to SLE clinical presentations in these children

Plasma endothelin-1 and nitric oxide in children with insulin-dependent diabetes mellitus

Dysfunction of vascular endothelium is considered an early step in the development of diabetic complications. To assess plasma endothelin-1 [ET-1] and nitric oxide [NO] levels in children with insulin-dependent diabetes mellitus [IDDM] and their relation to the degree of metabolic control and disease duration. Plasma ET-1 and NO levels were assessed-by enzyme immunoassay-in 34 children with IDDM and compared to 17 healthy controls of matched age and sex. Diabetic patients had higher plasma ET-1 levels compared to controls [median [IQR]=5.9 [4.9-39.2] Vs 4.9 [4.4-6.1] pg/mI, P=0.02]. ET-1 levels were higher in patients with poor and moderate metabolic control when compared to those with ideal control [p=0.004 and 0.001; respectively]. ET-1 levels were positively correlated with NO levels [r=0.48, p=0.004]; HblAc level [r=0.57, P=0,001]; and disease duration [r=0.39, p=0.02]. Although, plasma NO levels in diabetic patients were not significantly different from controls [median [IQR]=24.6 [21.9-30.2] Vs 22.0 [21.0-26.5] umol/L, P 0.09]; NO levels were significantly higher in patients with poor metabolic control when compared to those with ideal control [p<0.001]. In children with IDDM, poor metabolic control and increased disease duration are associated with increased ET-1 production, which may be related to future diabetic complications. The elevated plasma NO levels in poorly controlled patients might mean a compensatory protective response towards increased ET-1 production

Transforming growth factor beta 1 in children with systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is a disease characterized by loss of immunologic tolerance to self-antigens. About two thirds of children with SLE develop renal involvement during the course of their disease. Transforming growth factor beta 1 [TGF-beta 1] has an inhibitory effect on the immune system and it plays a central role in the pathogenesis of renal diseases. To assess plasma and urinaly TGF beta1 levels in children with active SLE and its possible role in the pathogenesis of the disease. Plasma and urinary [latent and active] TGF-beta 1 levels were assessed-by ELISA-in 32 children with active SLE and compared to 15 healthy controls of matched age and sex. Plasma latent and active TGF-beta 1 levels in children with active SLE were significantly lower than controls [median [IQR]=9.75 [9-27.6] Vs 18.9 [16-30] ng/mI,=0.004 and 0.38 [0.3-0.4] Vs 0.9 [0.8-1] ng/ml, p<0.001; respectively]. Plasma active TGF-beta 1 correlated negatively with Systemic Lupus Erythematosus Disease Activity Index [r=-0.38, P=0.03]. On the contrary; urinary latent and active TGF-beta 1 levels in children with active SLE were significantly higher than controls [median [IQR]=2.1[1.9-6.4] Vs 1.1[0.9-1.9] ng/mg creatinine, p<0.001 and 1.2 [1.07-1.53] Vs 0.7 [05-1] ng/mg creatinine, p=0.003; respectively]. Urinary active TGF-beta 1 levels correlated positively with Anti-ds DNA titer [r=0.42, p=0.015] and negatively with serum C3 levels [r=-0.48, p=0.005]. Patients with symptomatic nephritis had significantly elevated active urinary TGF-beta 1 levels in comparison to children with silent nephritis [P=0,008].In children with active SLE, lowered plasma TGF-beta 1 levels may be a feature of systemic immune dysfunction, which may have a role in the pathogenesis of the disease. On the other hand; increased renal production of TGF-beta 1 plays an important role in the pathogenesis and clinical presentation of lupus nephritis