Human Leukocyte Antigen (HLA) Typing Study Identifies Maternal DQ2 Susceptibility Alleles among Infertile Women: Potential Associations with Autoimmunity and Micronutrients

Background. The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status. Methods. Consecutive women (n = 187) with infertility and RSA, and controls (n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated. Results. DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency. Conclusion. Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.

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TagSNP approach for HLA Risk Allele Genotyping of Saudi Celiac Disease Patients: Effectiveness and Pitfalls

Bioscience Reports ◽

10.1042/bsr20210509 ◽

2021 ◽

Author(s):

Reham Baaqeel ◽

Babajan Banaganapalli ◽

Hadiah Bassam Al Mahdi ◽

Mohammed A. Salama ◽

Bakr H. Alhussaini ◽

...

Keyword(s):

Celiac Disease ◽

Local Population ◽

Human Leukocyte ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Leukocyte Antigen ◽

Tag Snps ◽

Ethnic Populations ◽

Hla Haplotypes ◽

Hla Dq2

Background: Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human Leukocyte Antigen (HLA) class II genes are known to act as high-risk markers for CD, where >95% of CD patients carry (HLA)- DQ2 and/or DQ8 alleles. Therefore, this study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag Single Nucleotide Polymorphisms (SNP).Methods: HLA-tag SNPs showing strong linkage value (r2>0.99) were used to predict the HLA DQ2 and DQ8 genotypes in 101 Saudi CD patients and in 103 healthy controls by using Real Time Polymerase Chain Reaction (RT-PCR) technique. Genotype calls were further validated by Sanger sequencing method.Results: A total of 63.7% of CD cases and of 60.2% of controls were predicted to carry HLA-DQ2 and DQ8 heterodimers, either in the homozygous or heterozygous states. The prevalence of DQ8 in our CD patients was predicted to be higher than the patients from other ethnic populations (35.6%). More than 32% of the CD patients were found to be non-carriers of HLA risk haplotypes as predicted by the tag SNPs.Conclusion: This study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared to the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases.

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Towards a Gamete Matching Platform: Using Immunogenetics and Artificial Intelligence to Predict Recurrent Miscarriage

10.1101/534594 ◽

2019 ◽

Author(s):

Aldo Mora-Sánchez ◽

Daniel-Isui Aguilar-Salvador ◽

Izabela Nowak

Keyword(s):

Artificial Intelligence ◽

Recurrent Miscarriage ◽

Human Leukocyte ◽

Allele Sharing ◽

Success Rates ◽

Leukocyte Antigen ◽

Hla Haplotypes ◽

Representation Techniques ◽

First Time ◽

Peptide Binding Affinity

AbstractThe degree of Allele sharing of the Human Leukocyte Antigen (HLA) genes has been linked with recurrent miscarriage (RM). However, no clear genetic markers of RM have yet been identified, possibly because of the complexity of interactions between paternal and maternal genes. We propose a methodology to analyse HLA haplotypes from couples either with histories of successful pregnancies or RM. This article describes, for the first time, a method of RM genetic-risk calculation. Novel HLA representation techniques allowed us to create an algorithm (IMMATCH) to retrospectively predict RM with an AUC = 0.71 (p = 0.0035) thanks to high-resolution typing and the use of linear algebra on peptide binding affinity data. The algorithm features an adjustable threshold to increase either sensitivity or specificity. Combining immunogenetics with artificial intelligence could create personalized tools to better understand the genetic causes of unexplained infertility and a gamete matching platform that could increase pregnancy success rates.

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Association of human leukocyte antigen haplotypes with clearance and persistence of hepatitis B virus infection in northeastern China

Epidemiology and Infection ◽

10.1017/s0950268814003902 ◽

2015 ◽

Vol 143 (13) ◽

pp. 2805-2812

Author(s):

H. Y. WANG ◽

F. WANG ◽

M. CHENG ◽

Y. LIU ◽

S. Y. ZHANG

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Northeastern China ◽

Hbv Infection ◽

Hla Typing ◽

Leukocyte Antigen ◽

B Virus ◽

Hla Haplotypes

SUMMARYThis study investigated clinical implications of human leukocyte antigen (HLA) I and II haplotypes, in combination with HBV sub-genotype C2, in hepatitis B virus (HBV) infections in northeastern China. Here, HLA haplotypes of 230 HBV-infected patients were compared to 210 healthy, unrelated Han individuals. Of the 230 HBV-infected patients, 54 had acute self-limited hepatitis (ASH) with sub-genotype C2 (ASH-C2), 144 had chronic hepatitis (CH) with sub-genotypes C2 and B2 (CH-C2 and CH-B2), and 32 spontaneously recovered without sub-genotype results. All groups underwent HLA typing and haplotype analysis. The results revealed that A*02-DRB1*12 and A*02-B*15-DRB1*09 carriers were susceptible to HBV infection. A*02-B*15-DRB1*09 is probably associated with acute onset and viral clearance and A*02-DRB1*12, with viral persistence. In HBV infections, B*40-DRB1*12 was associated with HBV persistence, whereas B*46-DRB1*09, A*24-DRB1*14, and B*15-DRB1*04 carriers easily recovered from the disease. By contrast, when infected with the HBV-C2 sub-genotype, A*24-DRB1*14, B*15-DRB1*04, A*02-B*15, A*02-DRB1*15, and A*02-B*15-DRB1*09 carriers displayed an acute clinical course before recovery. This study reveals a relationship between HLA haplotypes and HBV pathogenesis, thereby providing potential therapeutic targets to treat HBV infection.

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The Role of HLA Antigens and Steroid Dose on the Course of COVID-19 of Patients After Kidney Transplantation

Frontiers in Medicine ◽

10.3389/fmed.2021.730156 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ivana Dedinská ◽

Petra Skálová ◽

Karol Graňák ◽

Matej Vnučák ◽

Tatiana Baltesová ◽

...

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Hla Antigens ◽

Human Leukocyte ◽

Kidney Transplant Recipients ◽

Leukocyte Antigens ◽

Multicenter Analysis ◽

Time Of Infection ◽

Independent Risk Factors ◽

Hla Dq2

Background: Kidney transplant recipients appear to be at higher risk for critical COVID-19. Our analysis aimed to identify the possible risk factors for a severe course of the COVID-19 disease and to determine the influence of selected human leukocyte antigens (HLAs) on the course of the disease.Methods: This is a retrospective, multicenter analysis that included patients that were confirmed to be severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive after kidney transplantation (KT). The group of patients was divided into two subgroups according to the course of the infection, as follows: non-hospitalized and hospitalized.Results: A total of 186 patients (men, 69.4%) with confirmed SARS-CoV-2 positivity were included in the group. The following independent risk factors for the outcome of hospitalization were identified: the age at the time of infection [odds ratio (OR) = 1.19, P < 0.0001], a body mass index (BMI) >29.9 kg/m2 (OR = 7.21, P < 0.0001), <7.5-mg prednisone dose/day (OR = 2.29, P = 0.0008), and HLA-DQ2 with a protective nature (OR = 0.05, P = 0.0034).Conclusions: Higher doses of corticosteroids (>7.5 mg/kg) in standard immunosuppressive regimes and HLA-DQ2 appear to be protective factors in our analysis.

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Human Leukocyte Antigen and Red Blood Cells Impact Umbilical Cord Blood CD34+ Cell Viability after Thawing

International Journal of Molecular Sciences ◽

10.3390/ijms20194875 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4875 ◽

Cited By ~ 1

Author(s):

Vanegas ◽

Galindo ◽

Páez-Gutiérrez ◽

González-Acero ◽

Medina-Valderrama ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Cell Viability ◽

Cord Blood ◽

Red Blood Cells ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Blood Cells ◽

Human Leukocyte ◽

Hla Typing ◽

Leukocyte Antigen

Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34+ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34+ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34+ cell count significantly impacted CD34+ viability after thawing, along with HLA-B or -C (R2 = 0.95, p = 0.01; R2 = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34+ cell viability, RBC depletion significantly improves it.

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Selected clinical parameters and changes in cardiac morphology and function assessed by magnetic resonance imaging in patients with rheumatoid arthritis and ankylosing spondylitis without clinically apparent heart disease

Clinical Rheumatology ◽

10.1007/s10067-021-05777-6 ◽

2021 ◽

Author(s):

Wojciech Tański ◽

Paweł Gać ◽

Angelika Chachaj ◽

Małgorzata Sobieszczańska ◽

Rafał Poręba ◽

...

Keyword(s):

Risk Factors ◽

Heart Disease ◽

Ventricular Myocardium ◽

Left Ventricular ◽

Pericardial Fluid ◽

Independent Effect ◽

Left Ventricular Myocardium ◽

Leukocyte Antigen ◽

Independent Risk Factors ◽

Occurrence Type

Abstract Background The aim of the study was to assess the relationship between the occurrence of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and the cardiac magnetic resonance (CMR) changes in people without clinically overt heart disease. Methods The study group consisted of 74 people (48.81 ± 11.35 years): 29 patients with RA, 23 patients with AS and 22 people from control group. Blood samples were taken to assess laboratory parameters, disease activity was determined using activity scales, and CMR was performed. Results It was shown that the factors independently related to higher left ventricular mass index are AS occurrence, human B27 leukocyte antigen occurrence, higher neutrophil gelatinase–associated lipocalin concentration (NGAL) and higher body mass index (BMI). The lower right ventricular ejection fraction is result of an independent effect of RA, AS and higher NGAL. RA presence, methotrexate use, higher rheumatoid factor titer, higher NGAL, older age and higher BMI should be considered independent risk factors for greater left ventricular myocardium water content. RA occurrence, AS occurrence, type 2 diabetes occurrence and a higher C-reactive protein concentration can be independently associated with a higher probability of non-ischemic left ventricular myocardium injury. Larger pericardial fluid volume is result of an independent effect of higher NGAL, higher anti-cyclic citrullinated peptide antibodies titer and higher DAS28 disease activity index. Use of steroids is protective factor against larger volume of pericardial fluid. Conclusions RA and AS in people without clinically apparent heart disease are associated with the occurrence of adverse changes in CMR. Key Points•RA and AS in people without clinically apparent heart disease are associated with the occurrence of adverse changes in CMR..•The independent risk factors for higher LVEF are AS occurrence, human B27 leukocyte antigen occurrence, higher NGAL concentration and higher BMI..•RA presence, methotrexate use, higher RF, higher NGAL, older age and higher BMI are independent risk factors for higher LV T2 ratio..•RA occurrence, AS occurrence, type 2 diabetes occurrence and a higher CRP are independently associated with a higher risk of non-ischemic LV myocardium injury..

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Performance Characteristics of Updated INNO-LiPA Assays for Molecular Typing of Human Leukocyte Antigen A (HLA-A), HLA-B, and HLA-DQB1 Alleles

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.2.430-432.2004 ◽

2004 ◽

Vol 11 (2) ◽

pp. 430-432 ◽

Cited By ~ 11

Author(s):

Karen De Vreese ◽

Rachel Barylski ◽

Fiona Pughe ◽

Miriam Bläser ◽

Colin Evans ◽

...

Keyword(s):

Performance Evaluation ◽

Human Leukocyte Antigen ◽

Molecular Typing ◽

Human Leukocyte ◽

Performance Characteristics ◽

Hla Typing ◽

Tissue Typing ◽

Leukocyte Antigen ◽

Antigen A ◽

Accuracy Rates

ABSTRACT We carried out a multicenter performance evaluation of three new DNA-based human leukocyte antigen (HLA) typing assays: INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1 Update. After optimization, the accuracy rates were all 100%, and the final observed resolutions were 99.4, 92.4, and 85.6%, respectively. These rapid and easy-to-perform assays yielded results fully concordant with other DNA-based tissue typing tests.

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Familial Pemphigus Vulgaris Occured in a Father and Son as the First Confirmed Cases

Case Reports in Dermatological Medicine ◽

10.1155/2016/1653507 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4

Author(s):

Ali Haydar Eskiocak ◽

Birgul Ozkesici ◽

Soner Uzun

Keyword(s):

Genetic Predisposition ◽

Human Leukocyte ◽

Pemphigus Vulgaris ◽

Hla Typing ◽

Enzyme Linked Immunosorbent Assay ◽

Leukocyte Antigen ◽

Hla Genes ◽

Mother And Daughter ◽

First Occurrence ◽

Father And Son

Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease of the skin and mucous membranes. Although there is some evidence pointing towards a genetic predisposition by some human leukocyte antigen (HLA) genes, familial occurrence of PV is very rare. Most of the familial PV cases so far reported have been in mother and daughter and in siblings. PV in father and son, as presented here, has not been reported in the literature before, except an unconfirmed report. The diagnosis of PV was established by histologic, cytologic studies and enzyme linked immunosorbent assay (ELISA) in Case1and by ELISA and BIOCHIP indirect immunofluorescence test in Case2. The son was responsive to moderate doses of methylprednisolone, with the treatment continuing with tapered doses. The father was in a subclinic condition; consequently, only close follow-up was recommended. HLA typing studies revealed identical HLA alleles of HLA-DR4 (DRB1⁎04) and HLA-DQB1⁎03in both of our cases; this had been found to be associated with PV in prior studies. Familial occurrences of PV and related HLA genes indicate the importance of genetic predisposition. The first occurrence of confirmed familial PV in father and son is reported here.

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