New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans

Klitz, W.; Maiers, M.; Spellman, S.; Baxter‐Lowe, L.A.; Schmeckpeper, B.; Williams, T.M.; Fernandez‐Viña, M.

doi:10.1034/j.1399-0039.2003.00103.x

Cited by 179Genetic Associations and EpidemiologyRenal Transplantation Outcomes and TreatmentsHematopoietic Stem Cell Transplantation

New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans

Klitz, W., Maiers, M., Spellman, S., Baxter‐Lowe, L.A., Schmeckpeper, B., Williams, T.M., Fernandez‐Viña, M.·2003·Tissue Antigens

DOI 10.1034/j.1399-0039.2003.00103.x

Open this paper in CoChat — free account

Abstract

Abstract: A collaborative study involving a large sample of European Americans was typed for the histocompatibility loci of the HLA DR‐DQ region and subjected to intensive typing validation measures in order to accurately determine haplotype composition and frequency. The resulting tables have immediate application to HLA typing and allogeneic transplantation. The loci within the DR‐DQ region are especially valuable for such an undertaking because of their tight linkage and high linkage disequilibrium. The 3798 haplotypes, derived from 1899 unrelated individuals, had a total of 75 distinct DRB1‐DQA1‐DQB1 haplotypes. The frequency distribution of the haplotypes was right skewed with haplotypes occurring at a frequency of less than 1% numbering 59 and yet constituting less than 12% of the total sample. Given DRB1 typing, it was possible to infer the exact DQA1 and DQB1 composition of a haplotype with high confidence (>90% likelihood) in 21 of the 35 high‐resolution DRB1 alleles present in the sample. Of the DRB1 alleles without high reliability for DQ haplotype inference, only *0401, *0701 and *1302 were common, the remaining 11 DRB1 alleles constituting less than 5% of the total sample. This approach failed for the 13 serologically equivalent DR alleles in which only 33% of DQ haplotypes could be reliably inferred. The 36 DQA1‐DQB1 haplotypes present in the total sample conformed to the known pattern of permissible heterodimers. Four DQA1‐DQB1 haplotypes, all rare, are reported here for the first time. The haplotype frequency tables are suitable as a reference standard for HLA typing of the DR and DQ loci in European Americans.

Integrity signals

Registry

Crossref · 10.1034/j.1399-0039.2003.00103.x

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

HLA-DQ6 was overrepresented within the small NMOSD cohort (9 out of 22 typed samples [41%] versus 15%-20% in Europe).
“Interestingly, HLA-DQ6 was overrepresented within our small NMOSD cohort (9 out of 22 typed samples [41%] versus 15%-20% in Europe 57,58 ; Table S5).”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [58]

Sorted by citations

The Journal of Clinical Investigation
Witkin, E. M. (2016) · Journal of the American Dietetic Association · doi:10.1016/0002-8223(94)92394-9 · Cited by 920 · see citing works
High-resolution HLA alleles and haplotypes in the United States population
Maiers, M. J., Gragert, L. A., & Klitz, W. (2007) · Human Immunology · doi:10.1016/j.humimm.2007.04.005 · Cited by 456 · see citing works
“The donor–recipient pair donor typing was subjected to a rigorous quality control program as previously described [ 3 ].”
MethodSelf-citation
Balancing selection and heterogeneity across the classical human leukocyte antigen loci: A meta-analytic review of 497 population studies
Solberg, O. D., Mack, S. J., Lancaster, A. K., Single, R. M., Tsai, Y., Sanchez‐Mazas, A., & Thomson, G. J. (2008) · Human Immunology · doi:10.1016/j.humimm.2008.05.001 · Cited by 345 · see citing works
Clinical Relevance of Pretransplant Donor-Specific HLA Antibodies Detected by Single-Antigen Flow-Beads
Amico, P., Hönger, G., Mayr, M., Steiger, J., Hopfer, H., & Schaub, S. (2009) · Transplantation · doi:10.1097/tp.0b013e3181a5e034 · Cited by 271 · see citing works
“HLA-DQ antigens were primarily inferred from the HLA-DR antigens, which are in strong linkage disequilibrium (12).”
Background
Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy
Alam, J., Jantan, I., & Bukhari, S. N. A. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.05.055 · Cited by 286 · see citing works
Common and Well-Documented HLA Alleles: 2012 Update to the CWD Catalogue
Mack, S., Cano, P., Hollenbach, J., He, J., Hurley, C. K., Middleton, D., Moraes, M., Pereira, S., Kempenich, J., Reed, E., et al. (2013) · Tissue Antigens · doi:10.1111/tan.12093 · Cited by 235 · see citing works
Self-citation
Common and well-documented HLA alleles: report of the Ad-Hoc committee of the american society for histocompatiblity and immunogenetics.
Cano, P., Klitz, W., Mack, S., Maiers, M., Marsh, S. G., Noreen, H., Reed, E., Senitzer, D., Setterholm, M., Smith, A. G., et al. (2007) · Human Immunology · doi:10.1016/j.humimm.2007.01.014 · Cited by 229
Self-citation
HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP.
Duquesnoy, R., & Askar, M. (2007) · Human Immunology · doi:10.1016/j.humimm.2006.10.003 · Cited by 225
Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide
Steere, A., Klitz, W., Drouin, E. E., Falk, B., Kwok, W., Nepom, G., & Lee, A. B.-L. (2006) · Journal of Experimental Medicine · doi:10.1084/jem.20052471 · Cited by 207 · see citing works
“The 42 rare haplotypes that were found only in the control population are not shown here, but a complete listing of haplotypes in the control population has been published previously (19).”
BackgroundSelf-citation
Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation
Ciurea, S. O., Thall, P. F., Wang, X., Wang, S. A., Hu, Y., Cano, P., Aung, F. M., Rondón, G., Molldrem, J. J., Korbling, M. J., et al. (2011) · Blood · doi:10.1182/blood-2011-06-362111 · Cited by 230 · see citing works
“In the present study DPA1 and DQA1 were not typed; possible DSA against alleles of these loci were examined by inferring the alleles likely to be present at these loci from the tight associations with alleles at the contiguous DPB1 and DRB1/DQB1 loci, respectively.(12,13) No transplants were performed in patients pres…”
Background
Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease
Gutierrez‐Achury, J., Zhernakova, A., Pulit, S. L., Trynka, G., Hunt, K. A., Romanos, J., Raychaudhuri, S., van Heel, D. A., Wijmenga, C., & de Bakker, P. I. W. (2015) · Nature Genetics · doi:10.1038/ng.3268 · Cited by 151 · see citing works
Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
Conde, L., Halperin, E., Akers, N. K., Brown, K., Smedby, K., Rothman, N., Nieters, A., Slager, S., Brooks-Wilson, A., Agana, L., et al. (2010) · Nature Genetics · doi:10.1038/ng.626 · Cited by 179 · see citing works
Multiple mismatches at the low expression HLA loci DP, DQ, and DRB3/4/5 associate with adverse outcomes in hematopoietic stem cell transplantation.
Fernández-Viña, M., Klein, J., Haagenson, M., Spellman, S., Anasetti, C., Noreen, H., Lee, A. B.-L., Cano, P., Flomenberg, N., Confer, D., et al. (2013) · Blood · doi:10.1182/blood-2013-02-481945 · Cited by 155 · see citing works
“Donor age, median (range), y 36 (18-60) 36 (19-59) 36 (18-60) .”
InfluentialSelf-citation
HLA‐DR and ‐DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study
Sapir-Pichhadze, R., Tinckam, K., Quach, K., Logan, A., Laupacis, A., John, R., Beyene, J., & Kim, S. (2015) · American Journal of Transplantation · doi:10.1111/ajt.12968 · Cited by 128
SARS-CoV-2–specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein
Keller, M. D., Harris, K. M., Jensen-Wachspress, M. A., Kankate, V. V., Lang, H., Lazarski, C. A., Durkee-Shock, J. R., Lee, P., Chaudhry, K., Webber, K., et al. (2020) · Blood · doi:10.1182/blood.2020008488 · Cited by 122 · see citing works
Mapping of Immune-Mediated Disease Genes
Ricaño-Ponce, I., & Wijmenga, C. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153450 · Cited by 118 · see citing works
Immunogenetic Risk and Protective Factors for the Idiopathic Inflammatory Myopathies
OʼHanlon, T. P., Carrick, D. M., Arnett, F. C., Reveille, J. D., Carrington, M. N., Gao, X., Oddis, C. V., Morel, P. A., Malley, J. D., Malley, K. G., et al. (2005) · Medicine · doi:10.1097/01.md.0000189818.63141.8c · Cited by 102 · see citing works
Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link
Scully, M., Brown, J., Patel, R., Mcdonald, V., Brown, C., & Machin, S. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03692.x · Cited by 100 · see citing works
Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes.
Duquesnoy, R., Awadalla, Y., Lomago, J., Jelinek, L., Howe, J., Zern, D., Hunter, B., Martell, J., Girnita, A., & Zeevi, A. (2008) · Transplant Immunology · doi:10.1016/j.trim.2007.10.001 · Cited by 94
Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans
Krause‐Kyora, B., Nutsua, M. E., Boehme, L., Pierini, F., Pedersen, D. D., Kornell, S.-C., Drichel, D., Bonazzi, M., Möbus, L., Tarp, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03857-x · Cited by 95 · see citing works
Risk stratification by the virtual crossmatch: a prospective study in 233 renal transplantations
Amico, P., Hirt-Minkowski, P., Hönger, G., Gürke, L., Mihatsch, M., Steiger, J., Hopfer, H., & Schaub, S. (2011) · Transplant International · doi:10.1111/j.1432-2277.2011.01235.x · Cited by 90
“In 32/132 deceased donors (24%), HLA-DQb antigens were not determined but inferred from the HLA-DRb antigens, which are in strong linkage disequilibrium [16].”
Background
Large-Scale Characterization of Natural Ligands Explains the Unique Gluten-Binding Properties of HLA-DQ21
Stepniak, D., Wiesner, M., de Ru, A. H., Moustakas, A., Drijfhout, J., Papadopoulos, G., van Veelen, P. V., & Koning, F. (2008) · Journal of Immunology · doi:10.4049/jimmunol.180.5.3268 · Cited by 90
“The association of HLA-DQ2 with CD is extraordinarily strong: approximately 95% of CD patients carry the DQ2 phenotype wheraes in general population the frequency of this allele is about 2030% [4,5].”
The Complexity of Human Leukocyte Antigen (HLA)-DQ Antibodies and Its Effect on Virtual Crossmatching
Tambur, A., Leventhal, J. R., Friedewald, J., & Ramon, D. S. (2010) · Transplantation · doi:10.1097/tp.0b013e3181f89c6d · Cited by 87
Clinical link between MHC class II haplotype and interferon-beta (IFN-β) immunogenicity
Barbosa, M. D. F. S., Vielmetter, J., Chu, S. Y., Smith, D. D., & Jacinto, J. M. (2005) · Clinical Immunology · doi:10.1016/j.clim.2005.08.017 · Cited by 99 · see citing works
Disease relevant HLA class II alleles isolated by genotypic, haplotypic, and sequence analysis in North American Caucasians with pemphigus vulgaris.
Lee, E. H., Lendas, K. A., Chow, S., Pirani, Y., Gordon, D., Dionisio, R. G., Nguyen, D., Spizuoco, A., Fotino, M., Zhang, Y., et al. (2006) · Human Immunology · doi:10.1016/j.humimm.2005.09.003 · Cited by 83
Islet autoimmunity and HLA markers of presymptomatic and clinical type 1 diabetes: joint analyses of prospective cohort studies in Finland, Germany, Sweden, and the U.S
Anand, V., Li, Y., Liu, B., Ghalwash, M., Koski, E., Ng, K., Dunne, J. L., Jönsson, J., Winkler, C., Knip, M., et al. (2021) · Diabetes Care · doi:10.2337/dc20-1836 · Cited by 83 · see citing works
Cell-surface MHC density profiling reveals instability of autoimmunity-associated HLA
Miyadera, H., Ohashi, J., Lernmark, Å., Kitamura, T., & Tokunaga, K. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74961 · Cited by 80 · see citing works
Utility of genetic risk scores in type 1 diabetes
Luckett, A. M., Weedon, M. N., Hawkes, G., Leslie, R. D., Oram, R. A., & Grant, S. F. A. (2023) · Diabetologia · doi:10.1007/s00125-023-05955-y · Cited by 80 · see citing works
Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases
Saggau, C., Bacher, P., Esser, D., Rasa, M., Meise, S., Mohr, N., Kohlstedt, N., Hutloff, A., Schacht, S.-S., Dargvainiene, J., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.08.005 · Cited by 79 · see citing works
Efficacy of Induction Therapy with ATG and Intravenous Immunoglobulins in Patients with Low‐Level Donor‐Specific HLA‐Antibodies
Bächler, K., Amico, P., Hönger, G., Bielmann, D., Hopfer, H., Mihatsch, M., Steiger, J., & Schaub, S. (2010) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2010.03093.x · Cited by 73
“antigens, which are in strong linkage disequilibrium (14).”
Background
The probability of identifying a 10/10 HLA allele-matched unrelated donor is highly predictable
Tiercy, J.-M., Nicoloso, G., Passweg, J. R., Schanz, U., Seger, R. A., Chalandon, Y., Heim, D. A., Güngör, T., Schneider, P., Schwabe, R., et al. (2007) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1705787 · Cited by 65 · see citing works
HLA‐A, ‐B, ‐C, and ‐DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population
Mack, S. J., Tu, B., Lázaro, A., Yang, R., Lancaster, A. K., Cao, K., Ng, J., & Hurley, C. K. (2008) · Tissue Antigens · doi:10.1111/j.1399-0039.2008.01151.x · Cited by 73 · see citing works
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes
Levy, H., Wang, X., Kaldunski, M. L., Jia, S., Kramer, J., Pavletich, S. J., Reske, M., Gessel, T., Yassai, M. B., Quasney, M. W., et al. (2012) · Genes and Immunity · doi:10.1038/gene.2012.41 · Cited by 69 · see citing works
Analysis of preformed donor-specific anti-HLA antibodies characteristics for prediction of antibody-mediated rejection in kidney transplantation.
Malheiro, J., Tafulo, S., Dias, L., Martins, L., Fonseca, I., Beirão, I., Castro-henriques, A., & Cabrita, A. (2015) · Transplant Immunology · doi:10.1016/j.trim.2015.01.002 · Cited by 67
Molecular Signatures Differentiate Immune States in Type 1 Diabetic Families
Chen, Y.-G., Cabrera, S. M., Jia, S., Kaldunski, M., Kramer, J., Cheong, S., Geoffrey, R., Roethle, M. F., Woodliff, J., Greenbaum, C., et al. (2014) · Diabetes · doi:10.2337/db14-0214 · Cited by 65 · see citing works
“Subjects were genotyped for HLA-DQB1 and haplotypes were inferred using Caucasian haplotype frequencies as described (24,28).”
Method
Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression
Jin, Y., Roberts, G., Ferrara, T., Ben, S., van Geel, N., Wolkerstorfer, A., Ezzedine, K., Siebert, J., Neff, C., Palmer, B., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08337-4 · Cited by 64 · see citing works
New reservoirs of HLA alleles: pools of rare variants enhance immune defense
Klitz, W., Hedrick, P. W., & Louis, E. J. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.06.007 · Cited by 65 · see citing works
Self-citation
Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression.
Snanoudj, R., Kamar, N., Cassuto, É., Caillard, S., Metzger, M., Merville, P., Thierry, A., Jollet, I., Grimbert, P., Anglicheau, D., et al. (2019) · Kidney International · doi:10.1016/j.kint.2018.12.029 · Cited by 61
Donor‐Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients
Levitsky, J., Kaneku, H., Jie, C.-F., Walsh, R., Abecassis, M., & Tambur, A. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13757 · Cited by 60 · see citing works
“linkage disequilibrium and haplotype frequencies based on ethnicity, as provided by the National Marrow Donor Program (16,17).”
Method
A combined DPA1∼DPB1 amino acid epitope is the primary unit of selection on the HLA-DP heterodimer
Hollenbach, J., Madbouly, A., Gragert, L., Vierra-Green, C., Flesch, S., Spellman, S., Begovich, A., Noreen, H., Trachtenberg, E., Williams, T., et al. (2012) · Immunogenetics · doi:10.1007/s00251-012-0615-3 · Cited by 59
“While the allele frequency distributions for DPA1 and DPB1 do not differ significantly from neutral expectations, the frequencies for the broad serological types DP1–DP4 are significantly more even than expected under neutrality, suggesting evidence for balancing selection for these specificities.”
BackgroundMethodInfluentialSelf-citation
The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis
Xue, J., Gochuico, B. R., Alawad, A. S., Feghali‐Bostwick, C. A., Noth, I., Nathan, S. D., Rosen, G., Rosas, I. O., Đačić, S., Ocak, İ., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014715 · Cited by 58 · see citing works
“Analyses are restricted to Caucasian subjects because ,5% of lung transplantation recipients in the discovery cohort were members of minority groups, and HLA allele frequencies can vary greatly among racial/ethnic subpopulations [29,30].”
BackgroundResult
HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset.
Fain, P., Babu, S., Bennett, D., & Spritz, R. (2006) · Pigment Cell Research · doi:10.1111/j.1600-0749.2005.00279.x · Cited by 59 · see citing works
HLA Markers DQ8 and DR53 Are Associated With Lymphocytic Hypophysitis and May Aid in Differential Diagnosis
Heaney, A. P., Sumerel, B., Rajalingam, R., Bergsneider, M., Yong, W. H., & Liau, L. M. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2702 · Cited by 64 · see citing works
“5% of white control subjects (including Hispanic groups) from a very large dataset of bone marrow transplant donors carry the DQ8 or DR53 haplotype (26).”
Background
Human leukocyte antigen and cytokine gene variants as predictors of recurrent Chlamydia trachomatis infection in high-risk adolescents.
Wang, C., Tang, J.-M., Geisler, W., Crowley-Nowick, P., Wilson, C. M., & Kaslow, R. (2005) · Journal of Infectious Diseases · doi:10.1086/428592 · Cited by 57
Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy
Levine, A. P., Chan, M., Sadeghi‐Alavijeh, O., Wong, E. K. S., Cook, H. T., Ashford, S. E., Carss, K., Christian, M. T., Hall, M., Harris, C. L., et al. (2020) · Journal of the American Society of Nephrology · doi:10.1681/asn.2019040433 · Cited by 65 · see citing works
Advances in HLA: practical implications for selecting adult donors and cord blood units.
Hurley, C., Wagner, J., Setterholm, M., & Confer, D. (2006) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2005.10.005 · Cited by 52
Landscape and Selection of Vaccine Epitopes in SARS-CoV-2Preprint
Smith, C. C., Entwistle, S., Willis, C., Vensko, S. P., Beck, W., Garness, J. A., Sambade, M., Routh, E. D., Olsen, K. S., Kodysh, J., et al. (2020) · bioRxiv · doi:10.1101/2020.06.04.135004 · Cited by 51 · see citing works
Positive and Negative Associations of Human Leukocyte Antigen Variants with the Onset and Prognosis of Adult Glioblastoma Multiforme
Tang, J.-M., Shao, W., Dorak, M., Li, Y.-F., Miike, R., Lobashevsky, E. S., Wiencke, J., Wrensch, M., Kaslow, R., & Cobbs, C. (2005) · Cancer Epidemiology, Biomarkers and Prevention · doi:10.1158/1055-9965.epi-05-0136 · Cited by 50 · see citing works
An NGS-based HLA haplotype analysis and population comparison between two cities in Rio de Janeiro, Brazil.
Vianna, R., Secco, D., Hanhoerderster, L., Motta, J., Cardoso, J., & Pôrto, L. C. (2020) · HLA · doi:10.1111/tan.13940 · Cited by 48
Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial
Bestard, O., Meneghini, M., Crespo, E., Bemelman, F., Koch, M., Volk, H., Viklicky, O., Giral, M., Banas, B., Ruiz, J., et al. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16563 · Cited by 47
A panel of human cell-based artificial APC enables the expansion of long-lived antigen-specific CD4+ T cells restricted by prevalent HLA-DR alleles.
Butler, M., Ansén, S., Tanaka, M., Imataki, O., Berezovskaya, A., Mooney, M., Metzler, G., Milstein, M. I., Nadler, L., & Hirano, N. (2010) · International Immunology · doi:10.1093/intimm/dxq440 · Cited by 46 · see citing works
Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes
Ostrov, D. A., Alkanani, A. K., McDaniel, K. A., Case, S. R., Baschal, E. E., Pyle, L. L., Ellis, S., Pöllinger, B., Seidl, K. J., Shah, V. N., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97739 · Cited by 54 · see citing works
A high degree of HLA disparity arises from limited allelic diversity: analysis of 1775 unrelated bone marrow transplant donor-recipient pairs.
Hurley, C., Fernández-Viña, M., Hildebrand, W., Noreen, H., Trachtenberg, E., Williams, T., Lee, A. B.-L., Begovich, A., Petersdorf, E., Selvakumar, A., et al. (2007) · Human Immunology · doi:10.1016/j.humimm.2006.09.004 · Cited by 44
Self-citation
The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes.
Mikk, M.-L., Kiviniemi, M., Laine, A., Härkönen, T., Veijola, R., Simell, O., Knip, M., & Ilonen, J. (2014) · Human Immunology · doi:10.1016/j.humimm.2013.09.008 · Cited by 43 · see citing works
cPRA Increases With DQA, DPA, and DPB Unacceptable Antigens in the Canadian cPRA Calculator
Tinckam, K., Liwski, R., Pochinco, D., Mousseau, M., Grattan, A., Nickerson, P., & Campbell, P. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13355 · Cited by 42
Correlation of sensitizing capacity and T-cell recognition within the Bet v 1 family
Kitzmüller, C., Zulehner, N., Roulias, A., Briza, P., Ferreira, F., Faé, I., Fischer, G., & Bohle, B. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.12.1928 · Cited by 38 · see citing works
Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies.
Yamamoto, H., Uchida, N., Matsuno, N., Ota, H., Kageyama, K., Wada, S., Kaji, D., Nishida, A., Ishiwata, K., Takagi, S., et al. (2014) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2014.06.024 · Cited by 37 · see citing works
Epidemiological and genetic correlates of incident Chlamydia trachomatis infection in North American adolescents.
Geisler, W., Tang, J.-M., Wang, C., Wilson, C. M., & Kaslow, R. (2004) · Journal of Infectious Diseases · doi:10.1086/425077 · Cited by 37
“50 ican adolescents ( , including 100 Hispanic and 44 Eun p 145 ropean Americans) in our study, the frequencies of A*23 differed ( ) from those seen elsewhere [25, 27, 28], whereas P .”
BackgroundResult
Immune Mechanisms and Pathways Targeted in Type 1 Diabetes
Jacobsen, L. M., Newby, B. N., Perry, D. J., Posgai, A. L., Haller, M. J., & Brusko, T. M. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1066-5 · Cited by 42 · see citing works
Evidence that HLA-DQ9 confers risk to celiac disease by presence of DQ9-restricted gluten-specific T cells.
Bodd, M., Tollefsen, S., Bergseng, E., Lundin, K., & Sollid, L. (2012) · Human Immunology · doi:10.1016/j.humimm.2012.01.016 · Cited by 35
Multi-locus HLA class I and II allele and haplotype associations with follicular lymphoma
Skibola, C., Akers, N. K., Conde, L., Ladner, M., Hawbecker, S., Cohen, F., Ribas, F., Erlich, H. A., Goodridge, D., Trachtenberg, E. A., et al. (2012) · Tissue Antigens · doi:10.1111/j.1399-0039.2012.01845.x · Cited by 35
The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation
Nguyen, H. T. D., Wong, G., Chapman, J., McDonald, S., Coates, P., Watson, N., Russ, G., D'Orsogna, L., & Lim, W. (2016) · Transplantation Direct · doi:10.1097/txd.0000000000000632 · Cited by 34
“However, the lack of acuity for all HLA-DR-DQ haplotypes introduces uncertainties.(28) Our study has focussed only on the risk of early acute rejection within 12 months.”
Background
HLA-DQ Barrier: Effects on cPRA Calculations
Tambur, A., Leventhal, J., Walsh, R., Zitzner, J. R., & Friedewald, J. (2013) · Transplantation · doi:10.1097/tp.0b013e3182a452a5 · Cited by 31
“(16), studying a large sample of European American subjects, demonstrated that there is strong linkage disequilibrium between the DQA1 and DQB1 loci in this homogenous Caucasian population.”
Background
HLA-DQA1*03:02/DQB1*03:03:02 is strongly associated with susceptibility to childhood-onset ocular myasthenia gravis in Southern Han Chinese.
Zhu, W.-H., Lu, J.-H., Lin, J., Xi, J., Lu, J., Luo, S.-S., Qiao, K., Xiao, B.-G., Lu, C.-Z., & Zhao, C. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.03.018 · Cited by 31 · see citing works
“16%) (Klitz et al., 2003; Trachtenberg et al., 2007).”
The immunopathogenesis of celiac disease reveals possible therapies beyond the gluten-free diet
McAllister, C. S., & Kagnoff, M. (2012) · Seminars in Immunopathology · doi:10.1007/s00281-012-0318-8 · Cited by 30 · see citing works
Single-nucleotide polymorphisms in the IL2RA gene are associated with age at diagnosis in late-onset Finnish type 1 diabetes subjects
Klinker, M. W., Schiller, J. J., Magnuson, V. L., Wang, T., Basken, J., Veth, K. N., Pearce, K. I., Kinnunen, L., Harjutsalo, V., Wang, X., et al. (2009) · Immunogenetics · doi:10.1007/s00251-009-0417-4 · Cited by 28 · see citing works
“HLA-DQA1-DQB1 haplotypes (HLA-DQ) and 4-digit resolution of HLA-DQA1 were then inferred using reported European Caucasian haplotype frequencies ( Klitz et al. 2003 ), and confirmed by the E-M algorithm.”
Method
Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein
Ruiter, B., Rozemuller, E., van Dijk, A. V., Garssen, J., Bruijnzeel-koomen, C., Tilanus, M., Knol, E., & van Hoffen, E. (2007) · International Archives of Allergy and Immunology · doi:10.1159/000098660 · Cited by 28
Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset
Golden, G. J., Wu, V. H., Hamilton, J. T., Amses, K. R., Shapiro, M. R., Japp, A. S., Liu, C., Pampena, M. B., Kuri-Cervantes, L., Knox, J. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59626-0 · Cited by 25 · see citing works
“Phasing of HLA-DQA1 and HLA-DQB1 genotypes was inferred via comparison with published haplotype frequencies from European Americans 104 .”
Impact of de novo donor‐specific anti‐HLA antibodies on grafts outcomes in simultaneous pancreas–kidney transplantation
Malheiro, J., Martins, L., Tafulo, S., Dias, L., Fonseca, I., Beirão, I., Castro-henriques, A., & Cabrita, A. (2016) · Transplant International · doi:10.1111/tri.12687 · Cited by 27
“The loci within the DR-DQ region present a tight linkage and high linkage disequilibrium as shown by a study done in a population with European ancestry [23].”
Background
Human leukocyte antigen–A, -B, -C, -DRB1 allele and haplotype frequencies in Americans originating from southern Europe: Contrasting patterns of population differentiation between Italian and Spanish Americans
Mack, S. J., Tu, B., Yang, R., Masaberg, C., Ng, J., & Hurley, C. K. (2010) · Human Immunology · doi:10.1016/j.humimm.2010.10.017 · Cited by 24 · see citing works
LIMITED HLA SEQUENCE VARIATION OUTSIDE OF ANTIGEN RECOGNITION DOMAIN EXONS OF 360 10/10 MATCHED UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANT DONOR - RECIPIENT PAIRS
Hou, L., Vierra-Green, C., Lazaro, A. M., Brady, C., Haagenson, M., Spellman, S., & Hurley, C. K. (2016) · HLA · doi:10.1111/tan.12942 · Cited by 25
“Although HLA-DQA1 was not typed at the time of transplant, the tight linkage between HLA-DQA1 and -DQB1 predicts that, if HLA-DQB1 is matched, HLA-DQA1 will also be matched (24).”
BackgroundSelf-citation
HLA DR and DQ alleles and haplotypes associated with clinical response to glatiramer acetate in multiple sclerosis
Dhib-Jalbut, S. S., Valenzuela, R. M., Ito, K., Kaufman, M., Picone, M. A., & Buyske, S. G. (2013) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2013.02.005 · Cited by 27 · see citing works
The rare HLA-DQA1*03-DQB1*02 haplotype confers susceptibility to type 1 diabetes in whites and is preferentially associated with early clinical disease onset in male subjects.
van Autreve, J. V., Weets, I., Gulbis, B., Vertongen, F., Gorus, F., & der Auwera, B. J. V. (2004) · Human Immunology · doi:10.1016/j.humimm.2004.04.004 · Cited by 24
Unrelated Stem Cell Donor HLA Match Likelihoods in the US Registry Incorporating HLA-DPB1 Permissive Mismatching
Gragert, L., Spellman, S. M., Shaw, B., & Maiers, M. (2022) · medRxiv · doi:10.1101/2022.11.14.22282311 · Cited by 23
Self-citation
Failed Genetic Protection: Type 1 Diabetes in the Presence of HLA-DQB1*06:02
Simmons, K. M., Mitchell, A. M., Alkanani, A. K., McDaniel, K. A., Baschal, E. E., Armstrong, T., Pyle, L. L., Yu, L., & Michels, A. W. (2020) · Diabetes · doi:10.2337/db20-0038 · Cited by 26 · see citing works
Prediction of duration and success rate of unrelated hematopoietic stem cell donor searches based on the patient's HLA-DRB1 allele and DRB1-DQB1 haplotype frequencies
Hirv, K., Bloch, K. E., Fischer, M. D., Einsiedler, B., Schrezenmeier, H., & Mytilineos, J. (2009) · Bone Marrow Transplantation · doi:10.1038/bmt.2009.53 · Cited by 23 · see citing works
The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura.
Sinkovits, G., Szilágyi, Á., Farkas, P., Inotai, D., Szilvási, A., Tordai, A., Rázsó, K., Réti, M., & Prohászka, Z. (2017) · Human Immunology · doi:10.1016/j.humimm.2016.11.005 · Cited by 22
Association with HLA DQ of early onset myasthenia gravis in Southeast Texas region of the United States
Deitiker, P., Oshima, M., Smith, R. G., Mosier, D. R., & Atassi, M. (2011) · International Journal of Immunogenetics · doi:10.1111/j.1744-313x.2010.00979.x · Cited by 22
“allele or haplotype based on a control data set (Klitz et al., 2003), and is a measure of significant deviations in the higher direction.”
BackgroundMethodInfluential
Association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt–Koyanagi–Harada disease
Liu, B., Deng, T., Zhu, L., & Zhong, J.-X. (2018) · Medicine · doi:10.1097/md.0000000000009914 · Cited by 21 · see citing works
Human genetic variation studies and HLA class II loci
Agrawal, S., Khan, F., & Bharadwaj, U. (2007) · International Journal of Immunogenetics · doi:10.1111/j.1744-313x.2007.00683.x · Cited by 21
“Frequency of DRB1*0301DQA1*0501-DQB1*0201 is found as high as 11% among Iranis and 12.7% and 13.4%, respectively, among English and American Caucasians (Klitz et al., 2003).”
BackgroundInfluential
Full-resolution HLA and KIR gene annotations for human genome assembliesPreprint
Zhou, Y., Song, L., & Li, H. (2024) · Genome Research · doi:10.1101/gr.278985.124 · Cited by 25 · see citing works
“The HLA class II region is highly structured (Klitz et al. 2003; Norman et al. 2017; Chin et al. 2023), which is commonly characterized by DR haplotype.”
A Diverse Repertoire of CD4 T Cells Targets the Immediate-Early 1 Protein of Human Cytomegalovirus
Ameres, S., Liang, X.-L., Wiesner, M., Mautner, J., & Moosmann, A. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00598 · Cited by 20 · see citing works
“However, DRB1*0701 is in linkage disequilibrium with DQA1*0201/DQB1*0202 as described (32), and thus carriers of this haplotype can instead target IE-1 through HLA-DQ-restricted CD4 T cells, as seen for two of our three donors with this haplotype (Table 1; Figure 3B).”
Background
Comparing transplant glomerulopathy in the absence of C4d deposition and donor‐specific antibodies to chronic antibody‐mediated rejection
Torres, I., Salcedo, M., Moreso, F., Sellarés, J., Castellá, E., Azancot, M., Perelló, M., Cantarell, C., & Serón, D. (2014) · Clinical Transplantation · doi:10.1111/ctr.12433 · Cited by 20
“In patients with positive HLA-DQ, the presence/ absence of DSA was assigned according to linkage disequilibrium for DR-DQ types (20).”
Method
Cord blood banks collect units with different HLA alleles and haplotypes to volunteer donor banks: a comparative report from Swiss Blood stem cells
Meyer-Monard, S., Passweg, J. R., Troeger, C., Eberhard, H., Roosnek, E., de Faveri, G. N., Chalandon, Y., Rovó, A., Kindler, V., Irion, O., et al. (2009) · Bone Marrow Transplantation · doi:10.1038/bmt.2008.391 · Cited by 20
HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney transplant patients.
Varga, M., Rajczy, K., Telkes, G., Hídvégi, M., Péter, A., Remport, Á., Korbonits, M., Fazakas, J., Toronyi, É., Sárváry, E., et al. (2008) · Nephrology, Dialysis and Transplantation · doi:10.1093/ndt/gfn111 · Cited by 18
“Since HLA-DQ3 has strong linkage disequilibrium with HLA-DR11 [ 13 ], we analysed the data concerning HLA-DR11 in complex with HLA-DQ3.”
Background
Association of HLA class II alleles with sensitization to cow dander Bos d 2, an important occupational allergen.
Kauppinen, A., Peräsaari, J. P., Taivainen, A., Kinnunen, T., Saarelainen, S. A., Rytkönen-Nissinen, M., Jeal, H., Jones, M. G., & Virtanen, T. (2012) · Immunobiology · doi:10.1016/j.imbio.2011.08.012 · Cited by 18 · see citing works
Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers
Lim, W. C., Costa, M. E. M. D., Godefroy, K., Jacquet, E., Gragert, L. A., Rondof, W., Marchais, A., Nhiri, N., Dalfovo, D., Viard, M., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1265469 · Cited by 15 · see citing works
DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life
Thomas, N., Dennis, J., Sharp, S. A., Kaur, A., Misra, S., Walkey, H., Johnston, D., Oliver, N., Hagopian, W., Weedon, M., et al. (2021) · Diabetologia · doi:10.1007/s00125-021-05513-4 · Cited by 17 · see citing works
Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease.
Choung, R., Mills, J., Snyder, M., Murray, J., & Gandhi, M. (2020) · Human Immunology · doi:10.1016/j.humimm.2020.01.006 · Cited by 17
HLA-DR-DQ haplotypes and type 1 diabetes in Macedonia.
Ilonen, J., Kocova, M., Lipponen, K., Sukarova-Angelovska, E., Jovanovska, A., & Knip, M. (2009) · Human Immunology · doi:10.1016/j.humimm.2009.03.014 · Cited by 17 · see citing works
Genetic association of HLA DQB1 with CD4+CD25+high T-cell apoptosis in type 1 diabetes
Glišić, S., Klinker, M. W., Waukau, J., Jailwala, P., Jana, S., Basken, J., Wang, T., Alemzadeh, R., Hagopian, W., & Ghosh, S. (2009) · Genes and Immunity · doi:10.1038/gene.2009.14 · Cited by 19 · see citing works
Why can Sensitization by a HLA-DR2 Mismatch lead to Antibodies that react also with HLA-DR1?
Marrari, M., & Duquesnoy, R. (2009) · Human Immunology · doi:10.1016/j.humimm.2009.03.005 · Cited by 17
The incidence of HLA-DQ2/DQ8 in Turkish children with celiac disease and a comparison of the geographical distribution of HLA-DQ
Basturk, A., Artan, R., & Yılmaz, A. (2017) · Gastroenterology Review · doi:10.5114/pg.2017.72099 · Cited by 16
“During the interpretation of the HLA-DQ2 and HLA-DQ8 allele levels, the detection of 0201 and 0202 for HLA-DQ2 B1 and the detection of 0302 for HLA-DQ8 B1 are regarded as positive [10].”
Background
HLA-DR7 and HLA-DQ2: Transgenic mouse strains tested as a model system for ximelagatran hepatotoxicity
Lundgren, H., Martinsson, K., Cederbrant, K., Jirholt, J., Mucs, D., Madeyski-Bengtson, K., Havarinasab, S., & Hultman, P. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184744 · Cited by 17 · see citing works
Fine-mapping the human leukocyte antigen locus in rheumatoid arthritis and other rheumatic diseases: identifying causal amino acid variants?
van Heemst, J., Huizinga, T., van der Woude, D., & Toes, R. (2015) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000165 · Cited by 15
“Figure 1a schematically depicts the variation in the HLA-DR b1 domain per amino acid of the top 15 most prevalent HLA-DRB1 chains present in the Caucasian population (together covering 91% of the variations in Caucasians [21]).”
Background
Interaction between Treg Apoptosis Pathways, Treg Function and HLA Risk Evolves during Type 1 Diabetes Pathogenesis
Glišić, S., & Jailwala, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036040 · Cited by 15 · see citing works
“[35].”
Association of HLA Class II alleles and haplotypes with cervical dystonia: HLA DR13-DQ6 (DQB1*0604) homozygotes are at greatly increased risk of cervical dystonia in Caucasian Americans
Deitiker, P., Oshima, M., Jankovic, J., Duane, D., Aoki, K., & Atassi, M. (2011) · Autoimmunity · doi:10.3109/08916934.2010.509121 · Cited by 15
Immunogenetic Correlates of Neisseria gonorrhoeae Infection in Adolescents
Geisler, W., Wang, C., Tang, J.-M., Wilson, C. M., Crowley-Nowick, P., & Kaslow, R. (2008) · Sexually Transmitted Diseases · doi:10.1097/olq.0b013e31816b6593 · Cited by 15
Mapping MHC-resident transplantation determinants.
Malkki, M., Gooley, T., Horowitz, M., Absi, L., Christiansen, F., Cornelissen, J., Dormoy, A., Dubois, V., Gagne, K., Gluckman, E., et al. (2007) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2007.05.007 · Cited by 15
Self-citation
microRNAs: Novel Markers in Diagnostics and Therapeutics of Celiac Disease
Chamani, E., Sargolzaei, J., Tavakoli, T., & Rezaei, Z. (2019) · DNA and Cell Biology · doi:10.1089/dna.2018.4561 · Cited by 13 · see citing works
“2 (Klitz et al. , 2003; Meresse et al. , 2009). downregulation and reduced expression concerns with miR-31-5p in children and miR-338-3p in the duodenum of adults suffering from CD. miR-21-5p upregulation is sig-niﬁcantly involved in the regulation of the immune response in the duodenum of CD…”

Authors: Klitz, W., Maiers, M., Spellman, S., Baxter‐Lowe, L. A., Schmeckpeper, B., Williams, T. M., & Fernandez‐Viña, M.
Affiliations: National Marrow Donor Program (US)
University of California, San Francisco (US)
American Red Cross (US)
University of New Mexico Health Sciences Center (US)
Corresponding author: Klitz, W.
ORCID: Maiers, M.
Spellman, S.
Baxter‐Lowe, L.A.
Williams, T.M.
Venue: Tissue Antigens
Publisher: Wiley
Published: 2003-09-16
Volume: 62
Issue: 4
Pages: 296-307
ISSN: 0001-2815 (ISSN-L)
1399-0039
DOI: 10.1034/j.1399-0039.2003.00103.x
OpenAlex: W1976319355
Cited by: 179
References: 0
Citations by year: 2026: 5 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 1 · 2021: 9 · 2020: 9 · 2019: 4 · 2018: 6 · 2017: 11 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 8 · 2012: 12
FWCI: 3.89
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Tissue Antigens (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords: HLA haplotype frequencies, HLA-DRB1, HLA-DQA1, HLA-DQB1, haplotype inference, linkage disequilibrium, European Americans, allogeneic transplantation, rare haplotypes
MeSH terms: Histocompatibility Antigens Class II, Gene Frequency, Haplotypes, Histocompatibility Testing, HLA-DQ Antigens, HLA-DR Antigens, Humans, Reference Standards, HLA-A Antigens, HLA-B Antigens, White People, HLA-DRB1 Chains, HLA-DQ alpha-Chains, HLA-DQ beta-Chains

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cited by

Record

About these checks