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

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.

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

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3270
Author(s):  
Paola Triggianese ◽  
Carlo Perricone ◽  
Erica De Martino ◽  
Arianna D’Antonio ◽  
Maria Sole Chimenti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Leukocyte Antigen ◽  
Infertile Women ◽  
Micronutrient Status ◽  
Independent Risk Factors ◽  
Hla Haplotypes ◽  
First Time ◽  
Hla Dq2

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.

scholarly journals Umbilical Cord Blood Units Cryopreserved in the Public Cord Blood Bank: A Breakthrough in iPSC Haplobanking?

2020 ◽  
Vol 29 ◽  
pp. 096368972092615
Author(s):  
Eun Youn Roh ◽  
Sohee Oh ◽  
Jong Hyun Yoon ◽  
Byoung Jae Kim ◽  
Eun Young Song ◽  
...  
Keyword(s):  
Cord Blood ◽  
Therapeutic Option ◽  
Human Leukocyte ◽  
Korean Population ◽  
Genomic Changes ◽  
The Public ◽  
Leukocyte Antigen ◽  
Induced Pluripotent ◽  
Efficient Option ◽  
Hla Haplotypes

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs. We analyzed a total of 27,904 Korean CBUs donated to the public CB bank. Low-to-intermediate resolution typing was performed for HLA-A, -B, and -DRB1 alleles, and individuals possessing homozygous HLA haplotypes were identified by direct counting. Moreover, the matching probabilities for zero-mismatch transplantation were calculated for 27,904 CBUs and 50,000,000 potential Korean patients. Among the preserved CBUs, 15 HLA-A, 40 HLA-B, and 13 HLA-DRB1 alleles as well as 48 homozygous HLA-A-B-DRB1 haplotypes were identified at serological equivalents (2 digits). The 48 identified homozygous haplotypes cumulatively matched 78.18% of the 27,904 Korean CB donors as zero HLA-mismatch iPSC sources. Among the combinations of 1,699 haplotypes with frequencies greater than 0.001%, assuming a population of 50 million, those 48 haplotypes can provide a match for 78.37% of potential Korean recipients. A practicable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs may be an efficient option in allogeneic iPSC therapy because this type of haplobanking may provide cell lines with optimal HLA matching for up to three-quarters of the Korean population.

scholarly journals The Phenotype of Celiac Disease Has Low Concordance between Siblings, Despite a Similar Distribution of HLA Haplotypes

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 479 ◽  
Author(s):  
Saana Kauma ◽  
Katri Kaukinen ◽  
Heini Huhtala ◽  
Laura Kivelä ◽  
Henna Pekki ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Environmental Factors ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Similar Distribution ◽  
Intestinal Malabsorption ◽  
Sibling Pairs ◽  
Leukocyte Antigen ◽  
Intestinal Symptoms ◽  
Hla Haplotypes

The factors determining the presentation of celiac disease are unclear. We investigated the phenotypic concordance and the distribution of human leukocyte antigen (HLA) risk haplotypes in affected siblings. One hundred sibling pairs were included. Clinical and histological parameters and HLA haplotypes were compared between the first diagnosed indexes and their siblings. The phenotype was categorized into gastrointestinal, extra-intestinal, malabsorption/anemia, and asymptomatic. The phenotype was fully concordant in 21 pairs. The most common concordant phenotype was gastrointestinal (14 pairs). Indexes had more anemia/malabsorption and extra-intestinal symptoms than siblings (45% vs. 20%, p < 0.001 and 33% vs. 12%, p < 0.001, respectively). Twenty siblings and none of the indexes were asymptomatic. The indexes were more often women (81% vs. 63%, p = 0.008). They were also more often seronegative (11% vs. 0%, p = 0.03) and younger (37 vs. 43 year, p < 0.001), and had more severe histopathology (total/subtotal atrophy 79% vs. 58%, p = 0.047) at diagnosis. The indexes and siblings were comparable in other disease features. Pairs with discordant presentation had similar HLA haplotypes more often than the concordant pairs. The phenotype was observed to vary markedly between siblings, with the indexes generally having a more severe presentation. HLA did not explain the differences, suggesting that non-HLA genes and environmental factors play significant roles.

scholarly journals Acute Systemic Immune Activation following Conjunctival Exposure to Staphylococcal Enterotoxin B

2006 ◽  
Vol 74 (10) ◽  
pp. 6016-6019 ◽  
Author(s):  
Govindarajan Rajagopalan ◽  
Michele K. Smart ◽  
Robin Patel ◽  
Chella S. David
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Activation ◽  
Human Leukocyte Antigen Class ◽  
Human Leukocyte ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Leukocyte Antigen ◽  
Systemic Immune Activation ◽  
Enterotoxin B ◽  
First Time

ABSTRACT Conjunctival exposure to the Staphylococcus aureus superantigen staphylococcal enterotoxin B (SEB) may occur accidentally, as a result of bioterrorism, or during colonization or infection of the external eye. Using human leukocyte antigen class II transgenic mice, we show for the first time that conjunctival exposure to SEB can cause robust systemic immune activation.

scholarly journals Technical note: AI-Track-tive: automated fission track recognition using computer vision (Artificial Intelligence)

2020 ◽  
Author(s):  
Simon Nachtergaele ◽  
Johan De Grave
Keyword(s):  
Artificial Intelligence ◽  
Neural Networks ◽  
Computer Vision ◽  
Deep Neural Networks ◽  
Fission Track ◽  
Detection Algorithm ◽  
Technical Note ◽  
Success Rates ◽  
Automatic Counting ◽  
First Time

Abstract. Artificial intelligence techniques such as deep neural networks and computer vision are developed for fission track recognition and included in a computer program for the first time. These deep neural networks use the Yolov3 object detection algorithm, which is currently one of the most powerful and fastest object recognition algorithms. These deep neural networks can be used in new software called AI-Track-tive. The developed program successfully finds most of the fission tracks in the microscope images, however, the user still needs to supervise the automatic counting. The success rates of the automatic recognition range from 70 % to 100 % depending on the areal track densities in apatite and (muscovite) external detector. The success rate generally decreases for images with high areal track densities, because overlapping tracks are less easily recognizable for computer vision techniques.

Influence of Human Leukocyte Antigen Haplotypes on Acute Graft Versus Host Disease Incidence after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2887-2887
Author(s):  
Sameer Gupta ◽  
Charu Aggarwal ◽  
Philip L. McCarthy ◽  
Swaminathan Padmanabhan ◽  
Minoo Battiwalla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Hla Haplotypes

Abstract There is increasing evidence that the Human Leukocyte Antigen (HLA) alleles may influence the incidence of acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT). Differential presentation of recipient antigens to donor-derived T-cells by the respective HLA molecules may be a responsible factor. We have reported a decreased rate of aGVHD in HLA DR15 positive patients (pt) undergoing alloHSCT for myeloid malignancies (Blood, 2006; 107:1970). We investigated the influence of different HLA alleles and the three most common HLA haplotypes in US Caucasians on grade 2–4 acute GVHD (graded using published criteria) in HLA matched alloHSCT. We conducted a retrospective review of 195 related and 70 unrelated consecutive first myeloablative alloHSCT pt treated from 01/1992 to 4/2005 at our center. HLA typing was determined by either molecular (n=176) or serologic (n=89) methods. Pt characteristics included: AML (n=84), CML (n=62), NHL (n=47), ALL (n=41), MDS (n=20), HD (n=7) and CLL (n=4); median age 39 years (range 6–66), < 40 years (n=130); Male (n=168), Female (n=97); Caucasian (>95%); Donor-Recipient Sex Mismatch (n=112); Total Body Irradiation (TBI) conditioning regimens (n=205); Etoposide/Cyclophosphamide(Cy)/TBI (n=122), Busulfan(Bu)/Cy (n=28), Bu/TBI (n=27), Thiotepa/TBI (n=23), Cy/TBI (n=22), Fludarabine/Melphalan (n=8), Thiotepa/Carboplatin (n=8) or other combinations (n=27) and peripheral blood stem cell source (n= 35). HLA Haplotypes analyzed for their effect on aGVHD were A1B8DR3 (n=25), A3B7DR15 (n=20) and A2B44DR4 (n=13). There was no significant difference in the pt characteristics (donor relation, conditioning regimen, donor-recipient sex match, diagnosis, age, gender, performance status, disease status at transplant, stem cell source and GVHD prophylaxis) by each of the three haplotypes. We analyzed prior published HLA alleles that were associated with an increased or decreased risk of aGVHD and pt characteristics for their effect on grade 2–4 aGVHD incidence. By univariate analysis, donor relation (unrelated vs. related, 52% vs. 38%, p=0.0002), HLA A2 (44% vs. 33%, p=0.05) and HLA B8 were associated with increased aGVHD (61% vs. 37%, p=0.005) whereas HLA B18 was associated with decreased aGVHD (19% vs. 43%, p=0.017) in contrast to prior reports using serological typing only. By multivariate analysis, HLA A2 (RR=1.5, 95%CI: 1.0 to 2.2, p=0.04), HLA B8 (RR=1.9, 95%CI: 1.1 to 3.0, p=0.01) and unrelated donor (RR= 1.9, 95%CI: 1.3 to 2.9, p=0.001) were associated with increased aGVHD. HLA haplotype multivariate analysis demonstrated increased risk of aGVHD with haplotypes A1B8DR3 and A2B44DR4 (A1B8DR3: 64% vs. 32%, RR 2.6, 95% CI: 1.1 to 5.9, p=0.012 and A2B44DR4: 61% vs. 39%, RR 3.5, 95% CI: 1.7 to 7.5, p=0.04) whereas haplotype A3B7DR15 had less aGVHD compared to others (18% vs. 42%, RR 0.31, 95%CI: 0.098 to 0.98, p=0.049). This is the first published report of the effect of HLA haplotypes on aGVHD incidence. Results of our haplotype analysis substantiate our findings of single allele effects of HLA A2, HLA B8 and HLA DR15 suggesting a differential effect on aGVHD incidence. The ability to predict aGVHD after alloHSCT using HLA haplotypes may improve outcomes by allowing for individualized GVHD prophylaxis regimens.

Human leukocyte antigen (HLA) haplotypes and clozapine induced agranulocytosis

1997 ◽  
Vol 42 (1) ◽  
pp. 102S
Author(s):  
St. Theodoropoulou ◽  
K. Tarassi ◽  
L. Lykouras ◽  
J. Hatzimanolis ◽  
G. Papageorgiou ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Hla Haplotypes

scholarly journals Donor-Specific Anti-Human Leukocyte Antigen Antibodies Predict Prolonged Isolated Thrombocytopenia and Inferior Outcomes of Haploidentical Hematopoietic Stem Cell Transplantation

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaosu Zhao ◽  
Xiangyu Zhao ◽  
Mingrui Huo ◽  
Qiaozhen Fan ◽  
Xuying Pei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Human Leukocyte Antigen ◽  
Cell Transplantation ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Fluorescent Intensity ◽  
Leukocyte Antigen ◽  
Blood And Marrow Transplantation ◽  
First Time

Prolonged isolated thrombocytopenia (PT) after allogeneic stem cell transplantation (allo-SCT) has a great impact on transplant outcome. In this study, we performed a retrospective analysis to investigate the association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with PT in 394 patients who underwent unmanipulated haploidentical blood and marrow transplantation (HBMT). For HLA antibody positive samples with a median fluorescent intensity (MFI) > 500, DSAs were further examined. A total of 390 patients (99.0%) achieved sustained myeloid engraftment. Of the 394 cases tested, 45 (11.4%) were DSA positive. The cumulative incidence of PT in this cohort of patients was 9.9 ± 1.5%. The incidence of PT was higher in patients with a MFI ≥ 1000 compared with those with a MFI < 1000 (16.8 ± 6.4% versus 7.4 ± 1.4%,P=0.05). Multivariate analysis showed that the presence of DSAs (MFI ≥ 1000) was correlated to PT (hazard ratio (HR) 3.262; 95% confidence interval (CI), 1.339–7.946;P=0.009) and transplant-related mortality (HR 2.320; 95% CI, 1.169–4.426;P=0.044). Our results, for the first time, suggest an association of DSAs with PT after unmanipulated HBMT. It would help screen out the suitable donor and guide intervention. This indicated that DSAs should be incorporated in the algorithm for unmanipulated HBMT.

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

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 &gt;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&gt;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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