Adnan A. Alsulaimani

Association between type 1, type 2 cytokines, diabetic autoantibodies and 25-hydroxyvitamin D in children with type 1 diabetes

AbstractPurpose Vitamin D may play a role in the pathogenesis of type 1 diabetes (T1D). The aim of the current study was to determine the possible association between 25-hydroxyvitamin D [25(OH)D] levels and circulating levels of type 1 and type 2 cytokines, as well as the pathophysiology of T1D in children.MethodsA total of 250 T1D patients and 250 sex- and age-matched T1D-free controls were screened for 25(OH)D, hemoglobin A1c (HbA1c), type 1 and type 2 cytokines, C-reactive protein (CRP) and bone mineral metabolism, as well as antibodies against insulin, glutamic acid decarboxylase (anti-GAD 65) and islet cells.ResultsOur data showed that the plasma level of 25(OH)D was significantly lower in T1D patients and that there was a significant negative correlation between 25(OH)D levels and HbA1c values. There was a significant association between deficient levels of 25(OH)D and higher levels of cytokines (IFN-γ, TNF-α, IL-6, IL-1β, IL-4 and IL-10) and CRP. Total blood hemoglobin, the hematocrit percentage, body mass index SDS values, phosphate and magnesium levels were significantly lower in T1D patients than in T1D-free subjects. The levels of parathyroid hormone and alkaline phosphatase were significantly higher in T1D patients. Higher levels of cytokines were significantly associated with deficient levels of 25(OH)D. Moreover, in T1D patients, higher levels of islet antibodies, anti-GAD antibodies and anti-insulin antibodies were significantly associated with deficient levels of 25(OH)D.ConclusionsIn type 1 diabetic children, deficient levels of 25(OH)D are associated with high levels of HbA1c, circulatory cytokines and antibody markers.

Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms

In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5’ nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns.

Sequence Diversity of VP4 and VP7 Genes of Human Rotavirus Strains in Saudi Arabia

Group A rotavirus is responsible for inducing severe diarrhea in young children worldwide. Rotavirus vaccines are used to control the disease in many countries. In the current study, the sequences of human rotavirus G and P types in Saudi Arabia are reported and compared to different relevant published sequences. In addition, the VP4 and VP7 genes of the G1P[8] strains are compared to different antigenic epitopes of the rotavirus vaccines. Stool samples were collected from children under 2 years suffering from severe diarrhea. Screening of the rotavirus-positive samples was performed with rapid antigen detection kit. RNA was amplified from rotavirus-positive samples by reverse transcriptase polymerase chain reaction assay for both VP4 and VP7 genes. Direct sequencing of the VP4 and VP7 genes was conducted and the obtained sequences were compared to each other and to the rotavirus vaccines. Both G1P[8] G1P[4] genotypes were detected. Phylogenetic analysis revealed that the detected strains belong to G1 lineage 1 and 2, P[8] lineage 3, and to P[4] lineage 5. Multiple amino acid substitutions were detected between the Saudi RVA strains and the commonly used vaccines. The current findings emphasize the importance of the continuous surveillance of the circulating rotavirus strains, which is crucial for monitoring virus evolution and helping in predicting the protection level afforded by rotavirus vaccines.

Changes in the Levels of Cytokines in Both Diabetic/Non-Diabetic Type I Children Living in a Moderate Altitude Area in Saudi Arabia

The aim of the present study was to investigate the possible effects of living in moderate altitude area on pro/anti-inflammatory cytokines profile (IFN-γ, TNF-α, IL-6, IL-1β, IL-10, and IL-4) among type I diabetic (T1D) and non- T1D children compared with those living at sea level area. A prospective clinical study was carried out at pediatric outpatient endocrine clinics in Taif City, which is a moderate altitude area in Saudi Arabia, that stands about 1800-2000 meters above sea-level; and in Mecca City, which is a sea level area, that lies in the middle west of Saudi Arabia. Hemoglobin A1c (HbA1c) percentage was estimated and cytokine measurements were performed in sera by flow cytometry using Cytometric Bead Array (CBA) technology. In this study we included 600 children who were consecutively enrolled (sex and age were matched). The HbA1c was statistically significantly higher in children living in moderate altitude compared to those living at sea level (overall p<0.001). Furthermore, T1D patients had higher values of serum cytokine levels (IFN-γ, TNF-α, IL-6, IL-1β, IL-4, and IL-10) in comparison to non-T1D control group (overall p<0.001). In conclusion, the data of the present study clearly showed that in both T1D and non-T1D children, moderate altitude-natives expressed high HbA1c and both pro-and anti-inflammatory cytokines. Type I diabetic children living in moderate altitude or at sea level showed elevated levels of IFN-γ, TNF-α, IL-6, IL-1β, IL-4, and IL-10 than control subjects. Glycemic control in non-diabetic children was affected by living in moderate altitude, however, HbA1c significantly increased in diabetic children living in moderate altitude.

Neonatal infections in Saudi Arabia: association with C-reactive protein, CRP -286 (C>T>A) gene polymorphism and IgG antibodies

BackgroundC-reactive protein (CRP) is a nonspecific, acute-phase protein that rises in response to infectious and non-infectious inflammatory processes. Infections are the single largest cause of neonatal deaths globally.The primary aim of this study is to examine the association between CRP gene polymorphism and serum levels of CRP in correlation with early onset sepsis (EOS) infection in newborns living in Taif city, Saudi Arabia. The second aim is to examine the relationship between specific IgG/IgG subclasses and early onset sepsis (EOS) infection among these newborns.MethodsStaphylococcus aureus (S. aureus) is one of the most common organisms related to sepsis infection in the newborn at King Abdel Aziz Specialist Hospital (KAASH). This study was conducted in Taif city, at KAASH’s neonatal intensive care unit between March and August 2012. Neonates were consecutively enrolled onto the study having met our inclusion criteria (as per our research protocol).The CRP concentration level was analysed using NycoCard® CRP Single Test. CRP -286 (C>T>A) A polymorphisms were analyzed using Pyrosequencing technology for CRP genotyping. IgG subclasses were analysed in the study population using ELISA.ResultLogistic regression analyses showed that the AA and AC genotypes were negatively associated amongst EOS neonates compared to suspected neonates. The frequency of CC and CT were significantly associated with the EOS neonates compared to the suspected group. The levels of specific IgG1, IgG2 and IgG3 antibodies were significantly lower amongst EOS compared to the suspected group.ConclusionsTaken together, the CRP-286 (C>T>A) A genotype polymorphism and specific IgG antibodies isotype levels can contribute to a reduced risk of EOS. Furthermore, CRP has a potential use in detecting EOS in neonates, which may mean earlier detection and management of EOS and subsequently better clinical outcome.

Inflammatory Cytokines in Neonatal Hypoxic Ischemic Encephalopathy and their Correlation with Brain Marker S100 Protein: A Case Control Study in Saudi Arabia

Background: Neonatal HIE is still one of the major causes of morbidity and mortality in the perinatal period. The effective management and early intervention for these infants depends on early identification of the condition. This study aimed to identifying biomarkers of inflammation in HIE in Saudi Arabia and their association with serum level of S100 protein.Patients and methods: 100 cases of full-term infants were classified into two groups. The first was comprised of normal healthy infants, while the second was composed of infants with hypoxic-ischemic encephalopathy. Blood gases, electrolytes, liver and renal functions were evaluated, along with some inflammatory cytokines IL1, IL6 and TNFα. Correlation between cytokine levels and S100 protein level was adjusted with time.Results: The hypoxic infants recorded decreased pH level and disturbed blood electrolytes in comparison with healthy control. Also, significant increase in serum levels of IL1, IL6 and TNFα was detected in hypoxic group. Positive correlation between serum cytokine levels and S100 protein was evident.Conclusion: The data revealed some of the vital inflammatory cytokines that were most affected due to a decreased blood pH in newborn babies. Such information is useful for predicting treatment to overcome the severe side-effects arising in cases of hypoxic-ischemic encephalopathy. The study predicted early diagnosis and treatment as important for the avoidance of serious complications.

The Potential Role of PTPN-22 C1858T Gene Polymorphism in the Pathogenesis of Type 1 Diabetes in Saudi Population

ABSTRACT Background: Recent investigations have reported an association between protein tyrosine phosphatase non-receptor type-22 (PTPN-22) gene polymorphism and susceptibility to the development of type 1 diabetes (T1D) in some populations and not in others. In this study, we aimed to investigate the association of PTPN-22 C1858T polymorphism with T1D in Saudi children. Methods: A cohort of 372 type 1 diabetic children and 372 diabetes-free subjects was enrolled in the current investigation. The PTPN-22 C1858T polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Our data showed that the frequency of CT and TT genotypes of PTPN-22 C1858T was higher in T1D children (17.7% and 4.3%, respectively) compared to healthy controls (4.8% and 1.6%, respectively), and both genotypes were statistically associated with T1D patients (OR = 4.4, 95% CI: 2.55–7.58, p < 0.001; and OR = 3.2, 95% CI: 1.23–8.28, p = 0.017, respectively). Moreover, the 1858T allele was significantly associated with T1D patients compared to the C allele (OR = 3.2, 95% CI: 1.59–6.88, p < 0.001). In addition, the T allele was significantly associated with elevated levels of HbA1c, anti-GAD, and anti-insulin antibodies (p < 0.001) and a lower concentration of C-peptide (p < 0.001) in T1D children. Conclusion: The data presented here suggests that the T allele of PTPN-22 C1858T polymorphism might be a risk factor for T1D development in Saudi children.

Ellagic acid reduces murine schistosomiasis mansoni immunopathology via up-regulation of IL-10 and down-modulation of pro-inflammatory cytokines production

Abstract Context: The main immunopathology in schistosomiasis mansoni consists of a granulomatous inflammatory and fibrosing reaction in the liver and intestine against tissue trapped parasite eggs, which is mediated by CD4+ T cells. Ellagic acid (EA), a natural phenolic compound found in fruits and nuts, has potent anti-oxidant and anti-inflammatory properties. Objective: The aim of the present study was to evaluate the potential effect of EA in the treatment of murine schistosomiasis mansoni and its induced immunopathology. Materials and methods: Mice were infected, each with 40 Schistosoma mansoni (S. mansoni) cercariae and treated with EA at a total dose of 600 mg/kg body weight. At week eight of infection, mice were sacrificed; worm and egg burden were estimated; hepatic granuloma volume and collagen fibers deposition were evaluated; splenocytes were prepared and cultured in the presence of S. mansoni antigens. Results: EA treatment did not show any significant effect on worm or egg burden. However, hepatic granuloma volume and collagen fibers deposition were largely reduced with EA treatment. EA treatment augmented specific IL-10 production in response to S. mansoni antigenic stimulation. However, specific IL-1β, IL-4, IL-12, IL-13, IL-17A, TNF-α and IFN-γ production were significantly reduced with ex vivo and in vivo EA treatment. Serum IgM and IgG levels significantly increased, whereas specific IgA and IgE levels did not significantly change with EA treatment. Conclusion: EA treatment modulates cellular and humoral immune responses of infected mice and leads to a significant reduction of liver pathology in acute murine schistosomiasis mansoni.

Thanatophoric dysplasia Variant in Identical Saudi Twins; Prenatal Diagnosis and Genetic Analysis

Abstract Thanatophoric dysplasia is the most common neonatal lethal skeletal dysplasia with an estimated incidence of 1 in 20,000 live births. This condition shares some similarity of radiological findings with other types of lethal skeletal dysplasias. Definite diagnosis is necessary for accurate medical and genetic counseling. Prenatal sonographic and molecular genetic diagnoses in identical twin pregnancy of variant phenotypic appearance TD type I, is presented here