Formation of donor-specific antibodies depends on the epitope load of mismatched HLAs in lung transplant recipients: A retrospective single-center study.

The development of donor-specific antibodies (DSA) has a significant impact on graft outcome in solid organ transplantation. Mismatched HLAs are recognized directly and indirectly by the recipient immune system. Both pathways occur in parallel and result in the generation of plasma cells, DSA, cytotoxic and T helper lymphocytes. Here, we present the results of an analysis of the epitope load of mismatched HLAs in a cohort of 220 lung transplant recipients using two in silico algorithms, HLAMatchmaker and PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes). De novo DSA (dnDSA) were detected by single antigen bead assays. The percentage of recipients who developed dnDSA was significantly higher in the group of patients who received lung transplants with a mismatching score above the detected threshold than in the group of patients who received lung transplants with a mismatching score below the threshold. In a multivariate Cox proportional hazard analysis, the PIRCHE-II score appeared to be a superior predictor of dnDSA formation. In addition, PIRCHE-II technology was shown to be useful in predicting separate dnDSA1 and dnDSA2 formation. We conclude that both algorithms can be used for the evaluation of the epitope load of mismatched HLAs and the prediction of DSA development in lung transplant recipients.

Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti-MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.

Transmission of Middle East Respiratory Syndrome Coronavirus Infections in Healthcare Settings, Abu Dhabi.

Middle East respiratory syndrome coronavirus (MERS-CoV) infections sharply increased in the Arabian Peninsula during spring 2014. In Abu Dhabi, United Arab Emirates, these infections occurred primarily among healthcare workers and patients. To identify and describe epidemiologic and clinical characteristics of persons with healthcare-associated infection, we reviewed laboratory-confirmed MERS-CoV cases reported to the Health Authority of Abu Dhabi during January 1, 2013-May 9, 2014. Of 65 case-patients identified with MERS-CoV infection, 27 (42%) had healthcare-associated cases. Epidemiologic and genetic sequencing findings suggest that 3 healthcare clusters of MERS-CoV infection occurred, including 1 that resulted in 20 infected persons in 1 hospital. MERS-CoV in healthcare settings spread predominantly before MERS-CoV infection was diagnosed, underscoring the importance of increasing awareness and infection control measures at first points of entry to healthcare facilities.

Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 among UAE Residents.

Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were compiled in patients admitted to a major hospital in the United Arab Emirates between April 2020 and January 2021. We identified 12 single-nucleotide polymorphisms associated with the critical COVID-19 condition: rs59241277, rs113574864, rs182901986, rs60349934, and rs113876500; rs4944076, rs4944997, rs4944998, rs4944979, and rs10898210; and rs11574018 and rs11574024. We report significant associations between genetic determinants of vitamin D metabolism and COVID-19 severity in the UAE population. Further research needed to clarify the mechanism of action against viral infection in vitamin D deficiency. These variants could be used with vaccination to manage the spread of SARS-CoV-2 and could be particularly valuable in populations in which vitamin D deficiency is common.

Seroprevalence of COVID-19 infection in the Emirate of Abu Dhabi, United Arab Emirates: a population-based cross-sectional study.

BACKGROUND: The United Arab Emirates (UAE) was the first country in the Middle East to report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serosurveys are essential to understanding the extent of virus transmission. This cross-sectional study aims to assess the seroprevalence of SARS-CoV-2 infection in the Emirate of Abu Dhabi. METHODS: Between 19 July and 14 August 2020, 4487 households were selected using a random sample stratified by region and citizenship of the head of household (UAE citizen or non-citizen). A cluster sample of 40 labour camps was selected. Data on socio-demographic characteristics, risk factors and symptoms compatible with coronavirus disease 2019 (COVID-19) were collected. Each participant was first tested by Roche Elecsys® Anti-SARS-CoV-2 assay, followed, when reactive, by the LIAISON® SARS-CoV-2 S1/S2 IgG assay. RESULTS: Among 8831 individuals from households, seroprevalence was 10·4% [95% confidence intervals (CIs) 9·5-11·4], with higher seroprevalence in Abu Dhabi and Al Ain regions compared with those in Al Dhafra. In households, we found no sex difference and UAE citizens had lower seroprevalence compared with those of other nationalities. Among 4855 workers residing in labour camps, seroprevalence was 68·6% (95% CI 61·7-74·7), with higher seroprevalence among workers from Southeast Asia. In households, individuals with higher body mass indexes demonstrated higher seroprevalences than individuals with normal weight. Anosmia and ageusia were strongly associated with seropositivity. CONCLUSIONS: The majority of household populations in the Emirate of Abu Dhabi remained unexposed to SARS-CoV-2. In labour camps, SARS-CoV-2 transmission was high. Effective public health measures should be maintained.

Trimester specific reference ranges for serum TSH and Free T4 among United Arab Emirates pregnant women.

BACKGROUND: The American Thyroid Association (ATA) recommended the establishment of population specific reference ranges for thyroid hormones during pregnancy. Initial studies conducted in the United Arab Emirates (UAE) in 2003 and 2004 on pregnant women published a considerably higher upper limit for thyroid stimulating hormone (TSH) than that proposed by ATA. The UAE was classified as a country with mild iodine deficiency at the time of this initial study. After the implementation of aggressive strategies to address iodine deficiency over the last decade, the UAE was recently declared as iodine sufficient. The current study re-evaluates the reference intervals for thyroid hormones for pregnant women in the UAE after the declaration of iodine sufficiency status. METHODS: TSH and free thyroxin (FT4) from 414 UAE national pregnant females were analyzed to determine trimester specific reference ranges. RESULTS: The upper limits of the TSH reference ranges were found to be significantly lower than previously reported, but still higher than those recommended by ATA in 2011.FT4 reference ranges were found to be slightly lower than previously reported. CONCLUSION: TSH trimester specific reference ranges in UAE national pregnant women are higher than those recommended by ATA in 2011 but in keeping with the latest guidelines published in 2017. This should be considered while interpreting thyroid function tests in this population. Further studies including urinary iodine measurement, body mass index and larger numbers per partition in this population are recommended.

Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus.

At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60±11.59years and 48.21±12.17years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p=0.011) and LDL-cholesterol (p=0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p=0.031) and the TT genotype was associated with lower LDL-cholesterol level (p=0.007). The frequency of AAT and GGC haplotypes was also different between groups (p=0.014; p=0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.

Vitamin D status among the juvenile population: A retrospective study.

Vitamin D deficiency is a clinical problem and recently we have shown that 82.5% of our entire study cohort had inadequate serum 25(OH)D levels. In this study, we analysed serum 25(OH)D levels of juvenile patients admitted to the Burjeel Hospital of VPS Health care in Abu Dhabi, United Arab Emirates (UAE) from October 2012 to September 2014. Out of a total of 7883 juvenile patients considered in this study, almost 58.1% of females and 43.3% of males in the age group of 1-18 years were found to have low serum 25(OH)D levels (<50nmol/L). According to the coefficient of variation, females had significantly higher variability among juveniles (63.8%) than males (49.9%). Among the juveniles group of patients, age appears to be an important determining factor for defining vitamin D deficiency.The risk of deficiency (<30nmol/L) was found to be present in 31.4% of patients in the age group of 10-12 years, followed by 50.4% of patients in the age group of 13-15 years and 52.9% of patients in the age group of 16-18 years. The analysed age groups of females were found to have lower levels of 25(OH)D than males. It is important and perhaps alarming to note that such high rate of vitamin D deficiency is present in the juvenile age.

The AGE-RAGE axis in an Arab population: The United Arab Emirates Healthy Futures (UAEHFS) pilot study.

AIMS: The transformation of the United Arab Emirates (UAE) from a semi-nomadic to a high income society has been accompanied by increasing rates of obesity and Type 2 diabetes mellitus. We examined if the AGE-RAGE (receptor for advanced glycation endproducts) axis is associated with obesity and diabetes mellitus in the pilot phase of the UAE Healthy Futures Study (UAEHFS). METHODS: 517 Emirati subjects were enrolled and plasma/serum levels of AGE, carboxy methyl lysine (CML)-AGE, soluble (s)RAGE and endogenous secretory (es)RAGE were measured along with weight, height, waist and hip circumference (WC/HC), blood pressure, HbA1c, Vitamin D levels and routine chemistries. The relationship between the AGE-RAGE axis and obesity and diabetes mellitus was tested using proportional odds models and linear regression. RESULTS: After covariate adjustment, AGE levels were significantly associated with diabetes status. Levels of sRAGE and esRAGE were associated with BMI and levels of sRAGE were associated with WC/HC. CONCLUSIONS: The AGE-RAGE axis is associated with diabetes status and obesity in this Arab population. Prospective serial analysis of this axis may identify predictive biomarkers of obesity and cardiometabolic dysfunction in the UAEHFS.

Familial glucocorticoid deficiency type 2 in two neonates.

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by glucocorticoid deficiency, elevated plasma adrenocorticotropic hormone (ACTH) levels and preserved aldosterone/renin secretion. Adrenocorticotropic receptor mutations occur in about 40% of patients (FGD type 1), whereas the rest of the cases are associated with a normal receptor (FGD type 2). More than 50 cases have been reported in the literature so far. We report two cases of type 2 FGD from two related families who presented in the newborn period with varying clinical features. Direct sequencing of the genomic DNA of the patients failed to reveal mutations or other defects in the coding sequence of the ACTH receptor. Linkage analysis excluded mutations on the MC2-R gene outside the coding region. To our knowledge, these are the first two cases of FGD reported from the Middle East.

Total vitamin D assay comparison of the Roche Diagnostics "Vitamin D total" electrochemiluminescence protein binding assay with the Chromsystems HPLC method in a population with both D2 and D3 forms of vitamin D.

This study compared two methods of assaying the 25-hydroxylated metabolites of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). A fully automated electrochemiluminescence assay from Roche Diagnostics and an HPLC based method from Chromsystems were used to measure vitamin D levels in surplus sera from 96 individuals, where the majority has the D2 form of the vitamin. Deming regression, concordance rate, correlation and Altman Bland agreement were performed. Seventy two subjects (75%) had a D2 concentration >10 nmol/L while the remaining twenty four subjects had vitamin D2 concentration of less than 10 nmol/L by HPLC. Overall, the Roche Diagnostics method showed a negative bias of -2.59 ± 4.11 nmol/L on the e602 as compared to the HPLC with a concordance rate of 84%. The concordance rate was 91% in samples with D2 of less than 10 nmol/L and 82% in those with D2 concentration >10 nmol/L. The overall correlation had an r value of 0.77. The r value was higher in samples with D2 levels of less than 10 nmol/L, r = 0.96, as compared to those with D2 values of greater than 10 nmol/L, r = 0.74. The observed bias had little impact on clinical decision and therefore is clinically acceptable.

Vitamin D deficiency and sun avoidance among university students at Abu Dhabi, United Arab Emirates.

This study offers evidence that vitamin D deficiency could be a major public health burden among young Emirati adults, mostly because of sun deprivation in a sun-blessed country. This study included a random sample of 138 females and 70 males tested for serum 25-hydroxyvitamin D [25(OH)D] status. To further evaluate the predictors of vitamin D status in this population, the study examined diet, obesity and sun exposure. In summer, the mean serum 25(OH)D concentration for females was 20.9 ± 14.9 nmol/L, whereas that for males was 27.3 ± 15.7 nmol/L. Females scored significantly higher than males on the sun avoidance inventory (SAI), indicating that females avoid sun exposure to a greater extent than males, possibly explaining the lower vitamin D status. A significant negative correlation also existed between SAI and vitamin D status (Pearson's r = -0.33; p < 0.01), but no significant association was evident between vitamin D status and body mass index (Pearson's r = 0.03; p = 0.33) or low dietary intake of vitamin D-fortified foods (Pearson's r = 0.08; p = 0.13). The mean serum 25(OH)D concentration for females tested in winter was 31.3 ± 12.3 nmol/L while in the summer, it was 20.9 ± 14.9 nmol/L. This difference was statistically significant, suggesting that seasonal variation plays an important role in vitamin D status in the United Arab Emirates. Fortification of foods and drinks with vitamin D, supplementation and sensible sun exposure are important steps toward minimizing vitamin D deficiency.

Failure of alphacalcidol (1alpha-hydroxyvitamin D3) in treating nutritional rickets and the biochemical response to ergocalciferol.

It has been previously documented that alphacalcidol (1alpha-hydroxyvitamin D3) is inefficient in healing rickets, partly because it results in a suboptimal rise in 1,25-dihydroxyvitamin D (1,25-(OH)2D) and partly because it fails to replenish the store of 25-hydroxyvitamin D (25-OHD). However, very few studies have actually documented this outcome. The aim was to document biochemically the response to alphacalcidol and subsequently the change in response to ergocalciferol. This study was conducted at our institution from January 2005 till December 2008. We included all patients referred to our clinic with active rickets after a failed course of alphacalcidol. At baseline the median (IQR) for PTH l7.1 (4.5-35.3) pmol/L, 25-OHD 29.0 (18-66.2) nmol/L, 1,25-(OH)2D 205 (158.2-311.2) pmol/L and ALP 676 (462.5-1101.7) IU/L. After 3 months treatment with ergocalciferol the concentrations changed markedly with biochemical healing: PTH 4.5 (3.9-7.5), 25-OHD 143.5 (101.5-206.5), 1,25-(OH)(2)D 277 (221.0-572.7), ALP 369 (302.2-438.0). The results confirm the biochemical and physiological basis for using ergocalciferol (or cholecalciferol) in nutritional rickets. Unfortunately these forms are not readily available in many geographic areas. This supply problem together with marketing strategies forces physicians to make an incorrect choice of medication. Treatment with ergocalciferol was either with intramuscular stosstherapy or drops for 3 months. The former ensures compliance and is associated with higher 25-OHD and 1,25-(OH)2D concentrations.

Prevalence of undiagnosed diabetes and quality of care in diabetic patients followed at primary and tertiary clinics in Abu Dhabi, United Arab Emirates.

AIMS: To investigate the prevalence of undiagnosed type 2 diabetes (T2D) at primary health care (PHC) clinics, and to assess the quality of care of diabetic patients followed at a tertiary hospital diabetes center in Abu Dhabi, United Arab Emirates (UAE). METHODS: Between May 2009 and October 2010, adult patients attending two PHC clinics, and adult diabetic patients attending the diabetes center, were invited to participate in the study. After overnight fast, participants returned for interview and laboratory tests. Undiagnosed T2D was defined by FPG ≥ 7.0 mmol/l or HbA1c ≥ 6.5%. Quality of care was assessed by reported care practices and achievement of internationally recognized targets. RESULTS: Out of 239 patients at PHC clinics without history of T2D, 14.6% had undiagnosed T2D, and 31% had increased risk of diabetes (FPG 5.6-7.0 mmol/l or HbA1c 5.7-6.5%). The independent predictors of undiagnosed T2D were age (adjusted OR per year 1.07, 95% CI 1.04-1.11, p < 0.001) and BMI ≥ 25 (adjusted OR 4.2, 95% CI 0.91-19.7, p = 0.033). Amongst all 275 diagnosed T2D patients, including those attending PHC clinics and those followed at the diabetes center, it was found that 40.1% followed dietary recommendations, 12% reported visiting a diabetes educator, 28.2% walked for exercise, and 13.5% attained recognized targets of HbA1c < 7%, blood pressure < 130/80 mmHg, and LDL cholesterol < 2.6 mmol/l. CONCLUSIONS: Almost half of the adult patients attending PHC clinics had undiagnosed T2D, or increased diabetes risk. Care practices, and achievement of treatment targets, were suboptimal.