Publications by authors named "Abdullah Al-Jurayyan"

7 Publications

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Association of single-nucleotide polymorphisms in tumour necrosis factor and human leukocyte antigens genes with type 1 diabetes.

Int J Immunogenet 2021 May 20. Epub 2021 May 20.

Research Center, King Fahad Medical City, Riyadh, Saudi Arabia.

Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive destruction of insulin-producing pancreatic beta cells. This multifactorial disease has a strong genetic component associated with the human leukocyte antigens (HLA) and non-HLA regions. In this study, we compared frequencies of HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) associated the genes coding for: toll-like receptors (TLRs), tumour necrosis factor (TNF), interleukin-1 (IL-1), interleukin-1 receptor type 1 (IL-1R1), interleukin-1 receptor antagonist (IL-1RN), interleukin-2 (IL-2) and interleukin-12B (IL-12B), between T1D patients and healthy controls. The aim was to identify frequency differences and linkage between these genetic markers in T1D patients and healthy controls. Twelve SNPs were investigated as follows: rs16944 (IL-1B), rs1143634 (IL-1B), rs1800587 (IL-1A), rs2069762 (IL-2), rs3212227 (IL-12B), rs2234650 (IL-1R1), rs315952 (IL-1RN), rs3804099 (TLR2), rs4986790 (TLR4), rs4986791 (TLR4), rs1800629 (TNF) and rs361525 (TNF). TaqMan genotype assay method was used for SNPs genotyping. HLA-DRB1* genes were typed by Sequence Specific Oligonucleotide Probe (SSOP). SPSS and SNPStats programs were used for the statistical analysis. Significant differences between T1D and control groups were found for the dominant model of rs361525 and rs1800629A:rs361525G genotypes for TNF. Increased frequencies of DRB1*03 and DRB1*04 and decreased frequencies of DRB1*07, DRB1*11 and DRB1*13 and DRB1*15 were observed in T1D patients compared with controls. However, the genotype, DRB1*07 with rs1800629A/G was associated with T1D. We have confirmed that DRB1*03 and DRB1*04 are associated with increased risk and DRB1*07, DRB1*11 and DRB1*13 and DRB1*15 with decreased risk of T1D. Also, the dominant model of rs361525A, and the rs1800629G:361525A genotype were associated with increased risk. The simultaneous presence of DRB1*07 and rs1800629A/G genotypes in 23 out of 27 DRB1*07 positive T1D patients implied that islet cell peptide processing may have been biased towards autoimmunity by upregulation of TNF associated intronic SNPs.
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http://dx.doi.org/10.1111/iji.12535DOI Listing
May 2021

Diagnosing Coeliac Disease During Mass-Screening of General Paediatric Population: Is Biopsy Avoidable?

J Pediatr Gastroenterol Nutr 2021 Apr 28. Epub 2021 Apr 28.

Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City College of Medicine, Alfaisal University Prince Abdullah bin Khalid Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University The department of Pathology and Clinical Laboratory Medicine, Immunology, Serology & HLA Laboratory section, King Fahad Medical City Department of Biostatistics, Research Services Administration, Research center at King Fahad Medical City Department of Medical Translational Sciences & European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.

Objectives: Studies evaluating the correlation between tissue transglutaminase IgA (TGA-IgA) levels and the degree of enteropathy in screening-detected coeliac disease (CD) patients from the general childhood population are scarce. The objectives of our study were (1) to evaluate the correlation between the TGA-IgA titre and the degree of enteropathy and (2) to evaluate whether the no-biopsy approach to diagnose CD in symptomatic patients proposed by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition could be extended to asymptomatic CD patients diagnosed during mass screening studies.

Methods: The present study is a sub-study of a cross-sectional mass screening study, "Exploring the Iceberg of Coeliacs in Saudi Arabia", conducted among school-aged children (6-15 years) in 2014-2015. The 93 biopsy-confirmed CD patients constituted the study cohort of the present study (mean age 11.4 ± 2.6 years; 24 males). TGA-IgA titres and EMA at the time of biopsy and grade of enteropathy were assessed, and HLA DQ 2.2/2.5/8 genotyping was performed.

Results: Thirty-four patients had TGA-IgA titres > 10X ULN (36%); all had villous atrophy with positive EMA and DQ 2.2/2.5/8. The sensitivity and specificity of a TGA-IgA titre > 10xULN in correctly diagnosing CD was 100%. There was a significant positive correlation between the anti-TGA-IgA titre and the severity of enteropathy (P < 0.001). There was no significant difference in the TGA-IgA titre between the asymptomatic and symptomatic CD patients.

Conclusions: Our results provide evidence that a TGA-IgA titre > 10X ULN correlates with villous atrophy in CD patients detected by mass screening.
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http://dx.doi.org/10.1097/MPG.0000000000003164DOI Listing
April 2021

Identification of the Key Regulators of Spina Bifida Through Graph-Theoretical Approach.

Front Genet 2021 6;12:597983. Epub 2021 Apr 6.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Spina Bifida (SB) is a congenital spinal cord malformation. Efforts to discern the key regulators (KRs) of the SB protein-protein interaction (PPI) network are requisite for developing its successful interventions. The architecture of the SB network, constructed from 117 manually curated genes was found to self-organize into a scale-free fractal state having a weak hierarchical organization. We identified three modules/motifs consisting of ten KRs, namely, , , , , , , , , , and . These KRs serve as the backbone of the network, they propagate signals through the different hierarchical levels of the network to conserve the network's stability while maintaining low popularity in the network. We also observed that the SB network exhibits a rich-club organization, the formation of which is attributed to our key regulators also except for and . The KRs that were found to ally with each other and emerge in the same motif, open up a new dimension of research of studying these KRs together. Owing to the multiple etiology and mechanisms of SB, a combination of several biomarkers is expected to have higher diagnostic accuracy for SB as compared to using a single biomarker. So, if all the KRs present in a single module/motif are targetted together, they can serve as biomarkers for the diagnosis of SB. Our study puts forward some novel SB-related genes that need further experimental validation to be considered as reliable future biomarkers and therapeutic targets.
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http://dx.doi.org/10.3389/fgene.2021.597983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056047PMC
April 2021

Deamidated Gliadin Antibodies: Do They Add to Tissue Transglutaminase-IgA Assay in Screening for Celiac Disease?

J Pediatr Gastroenterol Nutr 2021 May;72(5):e112-e118

Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City.

Objectives: Use of deamidated gliadin peptide (DGP) test kits as adjunctive to tissue-transglutaminase-IgA (TTG-IgA) for the diagnosis of celiac disease (CD) has been a controversial issue. The objectives of our study were to evaluate the diagnostic performance of DGP antibodies compared with TTG-IgA and to evaluate the correlation between DGP-antibody titers and degree of enteropathy.

Methods: We included children who underwent endoscopy and biopsies because of positivity of any of the serology tests in the "celiac profile" (TTG-IgA, DGP-IgA, and DGP-IgG) from 2012 to 2019. We divided children into clinically suspected cases of CD (group 1) and asymptomatic cases screened as they were from a high-risk group (group 2).

Results: Group 1 constituted 52 children and group 2 included 81 children (76 type-1 diabetes [T1D]). The sensitivity and positive-predictive value (PPV) of DGP-IgG in group 1 (90%, 98%) and group 2 (91%, 85.5%) were comparable with TTG-IgA (98%, 92% in group 1; 100%, 80% in group 2). By adding DGP-IgG to TTG-IgA, the performance of TTG-IgA has improved marginally in group 1 (sensitivity 100%, PPV 92.3%). All cases with DGP-IgG titer 2 times ULN in group 1, and >4 times ULN in group 2 had villous atrophy. All T1D patients with TTG IgA >10 times ULN had villous atrophy.

Conclusions: DGP-IgG assay did not add to the performance of TTG-IgA. DGP-IgG titer correlated with enteropathy. The diagnosis of CD can be made in asymptomatic T1D child with TTG-IgA titer >10 times ULN and positive endomyseal antibodies.
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http://dx.doi.org/10.1097/MPG.0000000000003022DOI Listing
May 2021

Association between antinuclear antibodies (ANA) patterns and extractable nuclear antigens (ENA) in HEp-2 cells in patients with autoimmune diseases in Riyadh, Saudi Arabia.

Intractable Rare Dis Res 2020 May;9(2):89-94

Immunology and HLA Laboratory, Pathology and Clinical Laboratory of Medicine, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia.

Antinuclear antibodies (ANA) and extractable nuclear antigens (ENA) are instrumental biomarkers crucial in the detection of autoimmune disorders (AID) such as systemic lupus erythematosus (SLE), Sjogren syndrome, . In the present study, an assessment of the most frequent ANA patterns associated with most detectable ENA that could be used as efficient prognostic markers in the diagnosis of autoimmune diseases was conducted. Data was retrospectively analyzed from AID patients, retrieved from the medical records of King Fahad Medical City, Riyadh, KSA, from January 2016 to October 2018 who underwent ANA immunofluorescence of HEp-2 cells and their ENA detection was studied. Of the 453 total patients, 39/55 AID males (71%) and 332/398 AID females (83.4%) exhibited ANA positivity. The most common pattern was speckled S-ANA (32.4%) in females and homogenous H-ANA pattern (25.4%) in males. The histones were found at higher frequency in different ANA patterns. anti-Sjogren syndrome related antigen A (SSA), anti-ribonucleoprotein antibody (RNP-Sm), and histones were observed to be associated with homogenous and speckled nuclear patterns. Frequencies of ENA in all ANA patterns were found significant at < 0.05 in males and < 0.001 in females. Spearman's rank correlation of ENA within and among the ANA patterns was non-significant. SSA was significantly correlated with RNP-Sm and Sm at < 0.05 and < 0.01, respectively. The extractable nuclear antigens SSA, RNP-Sm, and histones were found associated with the S-ANA and H-ANA patterns. These correlations are of relevance for the accurate diagnosis of autoimmune diseases.
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http://dx.doi.org/10.5582/irdr.2020.03012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263989PMC
May 2020

Where are we today with infection among healthy children in Saudi Arabia?

Saudi J Gastroenterol 2019 Sep-Oct;25(5):309-318

The Division of Pediatric Infectious disease, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

Background/aims: The available studies on Helicobacter pylori (H. pylori) prevalence among healthy asymptomatic population across Saudi Arabia suffers from significant limitations. We conducted this large population-based study to estimate the H. pylori seropositivity rate among apparently healthy children in Saudi Arabia, using anti-H. pylori immunoglobulin A (IgA) and IgG serology tests, and to study the influence of H. pylori infection on growth.

Materials And Methods: We conducted a cross-sectional study to screen apparently healthy school aged Saudi children (aged 6-15 years), attending primary and intermediate schools in Riyadh between 2014 and 2016, for H. pylori seropositivity by checking for the presence of anti-H. pylori IgG and IgA antibodies in serum specimens.

Results: Out of 3551 serum specimens, 1413 cases tested seropositive for H. pylori organism (40%): 430 (12.2%) were both IgG and IgA positive, 212 (6%) and 771 (21.7%) cases showed isolated positivity for IgG or IgA, respectively. Male gender, older age, lower levels of socioeconomic status (SES), and family members >10 were significantly associated with H. pylori seropositivity. The proportion of participants with short stature was significantly more in the H. pylori seropositive group than the seronegative group (OR1.249, confidence interval [1.020-1.531], P= 0.033). There was no significant association between H. pylori seropositivity and gastrointestinal symptoms.

Conclusion: The prevalence of H. pylori seropositivity among apparently healthy Saudi children (40%) is intermediate compared with that in developed and developing countries. The Saudi pediatric population shows a predominant IgA-type immunological response to H. pylori infection.
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http://dx.doi.org/10.4103/sjg.SJG_531_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784433PMC
April 2020

Association of the genetic diversity of killer cell immunoglobulin-like receptor genes and HLA-C ligand in Saudi women with breast cancer.

Immunogenetics 2017 Feb 15;69(2):69-76. Epub 2016 Sep 15.

Zoology Department, College of Sciences, King Saud University, Post Office Box 2455, Riyadh, 11451, Saudi Arabia.

Breast cancer (BC) progression and metastases have been linked to antitumor immunity inefficiency and particularly to natural killer (NK) cells. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic receptors of NK cells. Through their interactions with human leukocyte antigen (HLA)-C ligands, they modulate NK and T cell actions against target cells. Therefore, we studied the combinatorial effect of KIR genes and their HLA-C ligands on the susceptibility to development of BC in Saudi women. The presence of KIR genes and HLA-C1 and HLA-C2 groups was typed in 50 Saudi patients living in Riyadh and 65 healthy controls using polymerase chain reaction with sequence-specific primers. Our results indicated a protective effect by the KIR2DS2, 2DS3, and 2DL5A genes against BC (OR = 0.25, 0.21, and 0.27, respectively, and p < 0.01). The synergistic action of the three genes was observed when they occurred together, and the absence of the three genes increased BC occurrence by 6.5-fold. Distribution of the HLA-C1/C2 ligand between patients and controls showed an increase in the risk of BC occurrence for the heterozygote C1/C2 (OR = 2.33; 95 % CI = 1.08-5.02; p = 0.037) and a protective effect of the homozygote C2C2 (OR = 0.03; 95 % CI = 0.009-0.098; p < 0.001). Combinatory analyses of KIR genes and their HLA-C ligands showed protective effects of KIR2DL2 and 2DL3 in the absence of their HLA-C1 ligand. These results suggested that KIR-gene content combined with their ligand could influence the risk of BC development in women in Saudi Arabia.
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http://dx.doi.org/10.1007/s00251-016-0950-xDOI Listing
February 2017