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Human leukocyte antigen‐G (HLA‐G) is classified as non‐classical HLA, located in the short arm of chromosome 6 and composed of seven introns and eight exons. The HLA‐G gene has a lower frequency polymorphism in the coding area and higher variability at the regulatory 5′‐ and 3′‐untranslated regions linked to HLA‐G microRNA regulation. HLA‐G molecule is known to have an immunomodulatory and tolerogenic features role. In 199 Saudi individuals, we examined the association between plasma soluble HLA‐G (sHLA‐G) levels and eight polymorphic different sites, including 14 bp ins/del/+3003T‐C/+3010C‐G/+3027C‐A/+3035C‐T/+3142C‐G/+3187A‐G/+3196C‐G single nucleotide polymorphisms (SNPs) in exon 8 in the HLA‐G gene. Our results revealed higher frequency for rs17179101C (97%), rs1707T (92%) and rs9380142A (73%) alleles. Greater frequencies for the tested genotypes were observed in 3027C/C (rs17179101) (93%), 14 bp (rs1704) ins/del (92%), +3003T/T (rs1707) (85%) and +3035C/T (rs17179108) (79%) SNP genotypes. Moreover, we observed a significant association of sHLA‐G with +3010G/C (rs1710) SNP. In conclusion, we showed a significant association between 3010G/C (rs1710) SNP and the sHLA‐G level among our sample for Saudi populations. Our findings demonstrated that specific SNP within the HLA‐G gene is linked to sHLA‐G molecule secretion, suggesting sHLA‐G levels may be regulated genetically. [ABSTRACT FROM AUTHOR]

Seroprevalence of SARS-CoV-2 IgG among health care workers (HCWs) is crucial to inform infection control programs. Conflicting reports have emerged on the longevity of SARS-CoV-2 IgG. Our objective is to describe the prevalence of SARS-CoV-2 IgG in HCWs and perform 8 months longitudinal follow-up (FU) to assess the duration of detectable IgG. In addition, we aim to explore the risk factors associated with positive SARS-CoV-2 IgG. The study was conducted at a large COVID-19 public hospital in Riyadh, Saudi Arabia. All HCWs were recruited by social media platform. The SARS-CoV-2 IgG assay against SARS-CoV-2 nucleocapsid antigen was used. Multivariable logistic regression was used to examine association between IgG seropositive status and clinical and epidemiological factors. A total of 2528 (33% of the 7737 eligible HCWs) participated in the survey and 2523 underwent baseline serological testing in June 2020. The largest occupation groups sampled were nurses [n = 1351(18%)], physicians [n = 456 (6%)], administrators [n = 277 (3.6%)], allied HCWs [n = 205(3%)], pharmacists [n = 95(1.2%)], respiratory therapists [n = 40(0.5%)], infection control staff [n = 21(0.27%], and others [n = 83 (1%)]. The total cohort median age was 36 (31–43) years and 66.3% were females. 273 were IgG seropositive at baseline with a seroprevalence of 10.8% 95% CI (9.6%-12.1%). 165/185 and 44/112 were persistently IgG positive, at 2–3 months and 6 months FU respectively. The median (25th– 75th percentile) IgG level at the 3 different time points was 5.86 (3.57–7.04), 3.91 (2.46–5.38), 2.52 (1.80–3.99) respectively. Respiratory therapists OR 2.38, (P = 0.035), and those with hypertension OR = 1.86, (P = 0.009) were more likely to be seropositive. A high proportion of seropositive staff had prior symptoms 214/273(78%), prior anosmia was associated with the presence of antibodies, with an odds ratio of 9.25 (P<0.001), as well as fever and cough. Being a non-smoker, non-Saudi, and previously diagnosed with COVID-19 infection by PCR were statistically significantly different by seroprevalence status. We found that the seroprevalence of IgG against SARS-CoV-2 nucleocapsid antigen was 10.8% in HCWs at the peak of the pandemic in Saudi Arabia. We also observed a decreasing temporal trend of IgG seropositivity over 8 months follow up period. [ABSTRACT FROM AUTHOR]

aimi,4 Fahad Almajhdi,1 Wael Alturaiki51Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Stem Cells Unit, Department of Cellular Therapy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Science, MNGHA, Riyadh, Saudi Arabia; 3Immunology and HLA Department, Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia; 4Research Center, King Fahad Medical City, Riyadh, Saudi Arabia; 5Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaCorrespondence: Wael AlturaikiDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaEmail [email protected] Background: Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in the Kingdom of Saudi Arabia, is associated with a high mortality rate. Aim: To determine the effect of MERS-CoV on the immune response in infected patients and investigate cytokine production in the A549 epithelial cell line in response to a recombinant MERS-CoV spike protein (rSP) in the presence or absence of anti-dipeptidyl peptidase 4 (DPP4) antibody (3 independent experiments). Cytokine levels were measured using a cytokine ELISA array. Methods: A Bio-Plex multiplex assay and cytokine ELISA were used in our study to measure the cytokine levels. Results: Comparative analysis of MERS-CoV-infected patients (4 samples) and noninfected healthy controls (HCs) (5 samples) showed that serum levels of the following cytokines and chemokines were significantly higher in MERS-CoV patients than in the HCs (*p < 0.05): interferon (IFN)-α 2 (43.4 vs 5.4), IFN-β (17.7 vs 6.2), IFN-γ (43.4 vs 9.7), interleukin (IL)-8 (13.7 vs 0), IL-2 (11.2 vs 3), IL-27p28 (57.8 vs 13.8), and IL-35 (167.5 vs 87.5). Discussion: Our results revealed that MERS-CoV infection induced a slight increase in IFN levels but triggered a more pronounced increase in expression of the regulatory cytokines IL-27 and IL-35. A recombinant version of the full-length MERS-CoV spike protein increased the expression of IL-8 (160 pg/mL), IL-2 (100 pg/mL) and IL-12 (65 pg/mL) in A549 lung epithelial cells compared to that in the unstimulated control cells. The presence of anti-DPP4 antibody did not affect cytokine suppression or induction in A549 cells in vitro but decreased the level of IL-8 from 160 pg/mL to 65 pg/mL. Conclusion: MERS-CoV can decrease IFN levels to interfere with the IFN pathway and enhance the production of regulatory cytokines. Inhibition of the increases in IL-27 and IL-35 may contribute to halting MERS-CoV in the early stage of infection. [ABSTRACT FROM AUTHOR]

Aims: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis.Methods: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package.Results: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4%; OR = 3.68; Pc < .0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6%; OR = 6.76; Pc < .0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0%; OR = 3.10; Pc = .0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7%; OR = 4.22; Pc = .0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7%; OR = 6.31; Pc = .0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; Pc = .0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; Pc < .0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; Pc < .0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; Pc = .0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction.Conclusions: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians. [ABSTRACT FROM AUTHOR]

There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. The antibody response is critical for vaccine-induced protection, and T follicular helper cells (TFH) are considered important for mediating the antibody response. Most data supporting the role for TFH in the antibody response are from animal studies, and direct evidence from humans is limited, apart from the presence of TFH-like cells in blood. We studied the activation and induction of TFH and their role in the anti-influenza antibody response induced by a live-attenuated influenza vaccine (LAIV) in human nasopharynx-associated lymphoid tissue (NALT). TFH activation in adenotonsillar tissues was analyzed by flow cytometry, and anti-hemagglutinin (anti-HA) antibodies were examined following LAIV stimulation of tonsillar mononuclear cells (MNC). Induction of antigen-specific TFH by LAIV was studied by flow cytometry analysis of induced TFH and CD154 expression. LAIV induced TFH proliferation, which correlated with anti-HA antibody production, and TFH were shown to be critical for the antibody response. Induction of TFH from naive T cells by LAIV was shown in newly induced TFH expressing BCL6 and CD21, followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced TFH was demonstrated by expression of the antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced TFH differentiation was inhibited by BCL6, interleukin-21 (IL-21), ICOS, and CD40 signaling blocking, and that diminished anti-HA antibody production. In conclusion, we demonstrated the induction by LAIV of antigen-specific TFH in human NALT that provide critical support for the anti-influenza antibody response. Promoting antigen-specific TFH in NALT by use of intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans. IMPORTANCE Airway infections, such as influenza, are common in humans. Intranasal vaccination has been considered a biologically relevant and effective way of immunization against airway infection. The vaccine-induced antibody response is crucial for protection against infection. Recent data from animal studies suggest that one type of T cells, TFH, are important for the antibody response. However, data on whether TFH-mediated help for antibody production operates in humans are limited due to the lack of access to human immune tissue containing TFH. In this study, we demonstrate the induction of TFH in human immune tissue, providing critical support for the anti-influenza antibody response, by use of an intranasal influenza vaccine. Our findings provide direct evidence that TFH play a critical role in vaccine-induced immunity in humans and suggest a novel strategy for promoting such cells by use of intranasal vaccines against respiratory infections. [ABSTRACT FROM AUTHOR]