Mannose binding lectin: serum level, gene polymorphism in SLE patients and its relation to lupus nephritis

Systemic lupus erythematosus [SLE] is an autoimmune disease in which the complement system plays a crucial role in its pathogenesis. Mannan-binding lectin [MBL] is a recognition molecule of the lectin pathway of complement activation. The presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations at MBL serum concentration. MBL variant alleles that lead to low serum levels and/or functional deficits of MBL are postulated to contribute to the susceptibility of SLE. Moreover, the influence of MBL variation on antibodies production and renal involvement in SLE patients remains controversial. MBL serum level and genotypes were studied in SLE patients with evaluation of its role in auto antibodies production and lupus nephritis development. MBL genotypes and serum level were screened in a case control study included 30 SLE patients as well as 30 healthy controls. MBL polymorphism at exon 1 codons 54 and 57 was detected by PCR using sequence-specific priming [SSP] and serum MBL level was determined by ELISA technique. There was predominance of AA genotype [80%] in control group. Genotype frequencies of MBL variants in patients with SLE showed significant differences when compared with controls [AA 53.3% vs 80%, P=0.03, OR = 0.29 and A O+O O 46.6% vs 20%, P = 0.03, OR =3.5, respectively]. Serum MBL in SLE patients [900 ng/ml] was significantly lower than that of the control group [2750 ng/ml, P = 0.001] with positive correlation with low MBL genotypes. SLE patients with mutant alleles were more likely to produce anti dsDNA [92.8% vs 75%, OR = 4.3] and anti-Smith antibodies [35.7% vs 18.7%, OR = 2.3]. Patients carrying MBL-low genotypes have an increased risk of development of lupus nephritis than those carrying MBL-high genotypes [64.7% vs 35.2%, P - 0.02, OR= 2.4]. MBL gene polymorphism associated with low MBL serum levels that were found with significantly increased frequency in SLE patients may be one of the genetic factors that determine the susceptibility to develop lupus nephritis

Nerve growth factor, neuropeptides and cutaneous nerves in atopic dermatitis

Neurogenic components, as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis [AD] with the neuroimmunocutaneous system as they modify the functions of immunoactive cells in the skin. Nerve growth factor [NGF] is the best-characterized member of the neurotrophin family. Both NGF and neuropepties may be associated with the disease pathogenesis. The aim of this study is to evaluate the plasma level of NGF and NPs in AD patients and to correlate them with the disease activity and with the nerve changes in the skin by electron microscopy. Plasma levels of NGF and vasoactive intestinal peptide [+VIP] were measured by an immunoenzymatic assay while plasma levels of calcitonine gene related peptide [CGRP] and neuropeptide Y [NPY] were measured by radioimmunoassay in 30 AD patients in comparison to 10 normal non-atopic controls. Electron microscopic study was done in 10 AD patients. It has been found that there is significant increase of plasma levels of NGF and NPs in AD patients compared with controls. There is a positive correlation between the plasma levels of NGF and disease activity [correlation coefficient=0.750, P<0.005]. There is a significant correlation of the number of Schwann axon complex, evidenced by electron microscopic examination and plasma level of NGF in AD patients. Neurogenic factors; NGF and NPs modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. NGF might be considered as a marker of the disease activity

Glutathione S-transferase gene T1 and ml polymorphism in type 2 diabetic patients with end-stage renal disease

Diabetes mellitus [DM] is associated with an increased production of reactive oxygen species [ROS] which may contribute to the development of diabetic nephropathy. Therefore, the levels of endogenous antioxidants may be one of determinants of the susceptibility to diabetic nephropathy. Glutathione S-transferases [GSTs] are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. Genetic polymorphisms of the genes coding for enzymes result in different phenotypes with respect to their ability to detoxify these agents. The present study was conducted to determine whether GSTM1 and GSTTl gene polymorphism influences the development of diabetic nephropathy in type 2 DM. The study population consisted of 80 subjects divided into 30 patients type 2 DM with diabetic related end-stage renal diseases [ESRD], 30 patients type 2 DM without nephropathy and 20 subjects apparently healthy individuals as a controls. Multiplex polymerase chain reaction [PCR] was used to analyze GSTM1 and GSTTl polymorphism. GSTTl and GSTM1 gene polymorphism occur more in diabetic patients with ESRD than diabetic patients without nephropathy [GSTM1 null genotype was present in 63% while GSTTl null genotype was present in 60% in group I]. Frequency of homozygous deletion of both GSTTl, GSTM1 was higher in diabetic patients with ESRD [53%] than patients without ESRD [10%], or control [5%], [p<0.05]. Significant negative correlation was found between presence of/GSTMl, GSTTl and albuminuria, serum creatinin and blood urea in diabetic patients with ESRD with a positive correlation between presence of gene GSTTl and GSTM1 null genotype and creatinine clearance where creatinine clearance was lower in patients with GSTT1and GSTM2 deletion, GSTM1 and GSTTl null genotype may play a significant role in the aetiopathogeneses and development of diabetic ESRD and may be a useful marker in the prediction of diabetic ESRD. Also, it can drive approch of genetic therapy in prevention of diabetic nephropathy

Serum levels of platelet-activating factor, platelet-activating factor acetylhydrolase, and tumor necrosis factor-alpha in neonates with necrotizing enterocolitis before and after treatment

Because previous investigations have suggested that platelet activating factor, and tumor necrosis factor,-alpha [TNF-alpha] are thought to be important mediators of experimental necrotizing enterocolitis in animals, we measured platelet activating factor [PAF], PAF-acetylhydrolase [PAF-AHs], and TNF-alpha in the serum of 23 human neonates with necrotizing enterocolitis before and 2 weeks after treatment and 14 age-matched control subjects with similar gestational ages, postnatal ages, and weights. Patients included in this study were studied from June 2002 to May 2004 at Neonatal Intensive Care Unit of Tanta University Hospital, Egypt Almost all patients with necrotizing enterocolitis had elevated serum platelet activating factor values [17.9 +/- 4.1 ng/ml vs. 3.7 +/- 0.8 ng/ml in control subjects, p < 0.01]. Serum acetylhydrolase activity was lower in patients than in control subjects [11.2 +/- 0.6 nmol/ml/min vs. 24.9 +/- 2.1 nmol/ml/min, p < 0.01]. Serum TNF-alpha concentration was significantly elevated in patients with necrotizing enterocolitis [119.2 +/- 63.1 U/ml vs. 5.7 +/- 1.7 U/ml, p < 0.01]. There were no significant differences between serum levels of PAF, TNF-alpha, and PAF-AHs between controls and survived patients 2 weeks after treatment, p>0.05. Also there were no significant differences between serum levels of PAF, TNF-alpha and PAF-AHs on admission between dead and survived patients, p>0.05. There was no correlation between individual platelet activating factor levels and both TNF-alpha and PAF-AHs levels in patients. We concluded that platelet activating factor and TNF-alpha are elevated in patients with necrotizing enterocolitis and that reduced platelet activating factor degradation contributes to the increased platelet activating factor levels, which together with TNF-alpha may con tribute to the pathophysiology of necrotizing enterocolitis in human neonates. The use of agents that antagonize or contain degrading factors of PAF might provide therapeutic and/or prophylactic options in the management of NEC

Rankl/OPG system is altered in hepatic osteodystrophy

The coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention. Hepatic Osteodystrophy has been established in patients with cholestatic liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases. Its etiology is complex and multifactorial. The Receptor activator of nuclear factor Kb ligand [RANKL] plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor [RANK] located on the surface of osteoclasts. This effect is counterbalanced by osteoprotegren [OPG], which acts as a decoy receptor competing with RANKL for RANK. In this study we aim to evaluate OPG/RANKL system in cirrhotic patients with backache. This study includes 50 subjects suffering backache, divided into 4 groups as follows: Group I:10 subjects with normal bone mineral density [BMD] as control, Group II: 10 patients with pathological BMD but who are otherwise healthy, Group III: 15 patients with cirrhosis and normal BMD, Group IV: 15 patients with cirrhosis and pathological BMD. All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD estimation. The lowest BMD values were estimated at the lumber spine, then femoral neck, and lastly lower end of radius. There was a significant decrease in OPG in osteopenic non cirrhotic patients compared to the control group, while it was significantly higher than controls in both osteopenic and non osteopenic patients of the cirrhotic groups. SRANKL was significantly higher in non cirrhotic patients with pathological BMD compared to the control group, but lower than controls in cirrhotic groups both with normal and pathological BMD, with a significant difference in cirrhotics with pathological BMD, and a non significant difference in those with normal BMD compared to controls. Serum OPG was negatively correlated to serum calcium, albumin, and INR, but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups. OPG/RANKL system plays a role in the pathogenesis of hepatic Osteodystrophy. In cirrhotic patients, low BMD has a tendency to affect axial bone earlier, which is similar to postmenopausal osteoporosis. However in cirrhosis there are higher OPG and lower sRANKL levels which are opposite to postmenopausal osteoporosis. This difference indicates that: either OPG/RANKL system is working in a different way in cirrhosis, which might be due to an increased RANK/RANKL affinity which is not measurable, and consumes part of total RANKL leaving a smaller amount of measurable soluble RANKL to be assessed, which would explain its lower level in serum despite increased osteoporotic changes in bone, or there are other factors associated with this process to make their mechanism of action different than in postmenopausal osteoporosis

Study of some biochemical and genetic markers in childhood simple obesity

This study was done to investigate the role of serum insulin, serum leptin, plasma adiponectin and lipoprotein lipase [LPL] Hind Ill gene polymorphism in childhood simple obesity for the development of group of disorders known as metabolic cardiovascular syndrome [MCS] which consists of an increased risk of hypertension, adverse lipid profile and early atherosclerotic lesions. This study was carried out on 20 children [6 boys and 14 girls] with simple obesity the diagnosis of simple obesity was based on the presence of body mass index [BMI] > 95[th] percentile with the exclusion of secondary obesity, their age was 8.2 +/- 2.28 years. Another 20 normal healthy children of matched age and sex served as a control group. All the studied groups were subjected to full clinical examination, anthropometric measurements, and estimation of blood glucose, lipid profile, serum insulin, serum leptin, plasma adiponectin as well as DNA analysis for detection of LPL Hind Ill gene polymorphism. Children with simple obesity showed significant increases in BMI, both systolic and diastolic blood pressure [SBP and DBP], serum triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-c], serum insulin and serum leptin levels. On the other hand they showed significant decreases in high-density lipoprotein cholesterol [HDL-c] and plasma adiponectin levels. Adverse lipid profile [high TG and low HDL-c], and/or elevated blood pressure were positively correlated with serum insulin and serum leptin but negatively correlated with plasma adiponectin. There was no significant difference in Hind Ill LPL gene frequency between obese children and control group. Adverse lipid profile and hyperinsulinemia were associated with LPL Hind Ill polymorphism. This association was highest with [+/+] genotype, intermediate with [ +/- ] genotype and lowest with [-/-] genotype. In conclusion: hyperinsulinemia, hypeileptinemia, hypoadiponectinemia and the [H+] allele of the LPL Hind Ill polymorphism are closely correlated with the adverse lipid profile and/or elevated blood pressure in children with simple obesity that are regarded as cardiovascular risk factors for adulthood atherosclerosis which may necessitate an early periodic monitoring of blood pressure and metabolic status as well as the future application of the promising therapeutic ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties