{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:40:10Z","timestamp":1792424410040,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The immune response in elderly individuals is influenced by genetic factors, particularly polymorphisms in major histocompatibility complex (MHC), such as human leukocyte antigen (HLA). Age-related changes in immune function, referred to as immunosenescence, can lead to the formation of RBC-bound antibodies, which may pose risks in transfusion medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to investigate the association between HLA-DQB1 alleles and the presence of RBC-bound antibodies in elderly individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A total of 83 healthy elderly (aged 60-70) samples were collected. Blood samples were processed by centrifugation at 3500 rpm for 10\u00a0min to obtain serum. RBCs were isolated through centrifugation at 3000 rpm, washed with saline, and 2% type O RBC was prepared. Serum (100 \u00b5L) was mixed with saline (100 \u00b5L) and 2% type O RBCs (50 \u00b5L), incubated at 37\u00a0\u00b0C for 30\u00a0min, and analyzed via flow cytometry. At the same time, control sample was also processed with equal volume. DNA was extracted using the sequence-based typing kit, and specific genes at the HLA DQB1 locus were amplified by PCR, confirmed through agarose gel electrophoresis and sequencing for allele identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RBC-bound antibodies were detected in 42 of 83 participants, indicating a higher index of agglutination (IAG), while 41 samples showed no RBC-bound antibodies, indicating negative IAG. The mean IAG was\n                      <jats:italic>-1.88<\/jats:italic>\n                      (\n                      <jats:italic>SD = 25.943<\/jats:italic>\n                      ), reflecting variability in immune reactions. Sequence based typing (SBT) analysis revealed a significant association between the HLA-DQB1*\n                      <jats:italic>04<\/jats:italic>\n                      allele and IAG\n                      <jats:italic>(p &amp;lt; 0.034)<\/jats:italic>\n                      , while no significant associations were found for alleles DQB1\n                      <jats:italic>*02, *03, *05, and<\/jats:italic>\n                      *\n                      <jats:italic>06.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study highlights the role of HLA-DQB1\n                      <jats:italic>*04<\/jats:italic>\n                      in the presence of RBC-bound antibodies in elderly individuals, emphasizing the complexities of immunosenescence and variability in immune responses within this population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1743789","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:53:28Z","timestamp":1784699608000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Detection of RBC-bound antibodies using flow cytometry and their correlation with HLA polymorphism"],"prefix":"10.3389","volume":"17","author":[{"given":"Anwar","family":"Ullah","sequence":"first","affiliation":[{"name":"College of Medical Laboratory, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Qi","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elp010","article-title":"The human major histocompatibility complex as a paradigm in genomics research","volume":"8","author":"Vandiedonck","year":"2009","journal-title":"Proteomics"},{"key":"B2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/B978-0-7020-6896-6.00005-3","article-title":"The major histocompatibility complex","volume-title":"Clinical Immunology","author":"Monos","year":"2019"},{"key":"B3","doi-asserted-by":"publisher","first-page":"944","DOI":"10.3390\/cells8090944","article-title":"MHC genomics and disease: looking back to go forward","volume":"8","author":"Dawkins","year":"2019"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-07-6471","article-title":"Comprehensive analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci and squamous cell cervical cancer risk","volume":"68","author":"Madeleine","year":"2008"},{"key":"B5","article-title":"Genetics, human major histocompatibility complex (MHC)","author":"Tumer","year":"2019"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2014.04.016","article-title":"Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine","volume":"75","author":"Samandary","year":"2014"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m110.148155","article-title":"HLA-DP, HLA-DQ, and HLA-DR have different requirements for invariant chain and HLA-DM","volume":"285","author":"van Lith","year":"2010"},{"key":"B8","first-page":"7","article-title":"The distributions of HLA\u2010A, HLA\u2010B, HLA\u2010C, HLA\u2010DRB1 and HLA\u2010DQB1 allele and haplotype at high\u2010resolution level in Zhejiang Han population of China","volume":"46","author":"Chen","year":"2019"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.3390\/cancers12051155","article-title":"MHC class I regulation: the origin perspective","volume":"12","author":"Sznarkowska","year":"2020"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2020.07.001","article-title":"Association of HLA class II (-DRB1,-DQB1,-DPB1) alleles and haplotypes on susceptibility to aplastic anemia in northern Chinese Han","volume":"81","author":"Qi","year":"2020"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6268514","article-title":"A novel putative role of TNK1 in atherosclerotic inflammation implicating the Tyk2\/STAT1 pathway","volume":"2020","author":"Bao","year":"2020","journal-title":"Mediators Inflammation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1469-1809.2001.6510001.x","article-title":"How selection shapes variation of the human major histocompatibility complex: a review","volume":"65","author":"Meyer","year":"2001"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0039-x","article-title":"HLA in transplantation","volume":"14","author":"Montgomery","year":"2018"},{"key":"B14","doi-asserted-by":"publisher","first-page":"5986740","DOI":"10.1155\/2018\/5986740","article-title":"Kidney transplantation: the challenge of human leukocyte antigen and its therapeutic strategies","volume":"2018","author":"Alelign","year":"2018"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado4188","article-title":"Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis","volume":"388","author":"Lin","year":"2025","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2174\/138920207783591690","article-title":"The HLA region and autoimmune disease: associations and mechanisms of action","volume":"8","author":"Simmonds","year":"2007"},{"key":"B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1201\/9780429282324-1","article-title":"HLA and autoimmunity","volume-title":"Perspectives on Autoimmunity","author":"de Vries","year":"2020"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2005.03.021","article-title":"HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms","volume":"14","author":"Thorsby","year":"2005"},{"key":"B19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3389\/fbioe.2019.00147","article-title":"Cell cytometry: review and perspective on biotechnological advances","volume":"7","author":"Vembadi","year":"2019"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1007\/978-981-97-4553-1_7","article-title":"Flow cytometry: revolutionizing cellular analysis in spectral and microfluidic dimensions","volume-title":"Flow Cytometry: Principles, Applications, and Clinical Perspectives","author":"Jyoti","year":"2024"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1159\/000079075","article-title":"Flow cytofluorometric analysis in red blood cell immunology","volume":"31","author":"Arndt","year":"2004"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/10408347.2022.2154596","article-title":"Flow cytometry\u2013sophisticated tool for basic research or\/and routine diagnosis; impact of the complementarity in both pre-as well as clinical studies","volume":"54","author":"Railean","year":"2024"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2010.03.001","article-title":"A critical review of published methods for analysis of red cell antigen-antibody reactions by flow cytometry, and approaches for resolving problems with red cell agglutination","volume":"24","author":"Arndt","year":"2010"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2021.1951426","article-title":"Highly sensitive detection of antibody nonspecific interactions using flow cytometry","author":"Makowski","year":"2021"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s12288-024-01915-7","article-title":"Establishment of flow cytometry-based assay for the quantitative measurement of erythrocyte agglutination in clinical laboratory","volume":"41","author":"Ullah","year":"2024"},{"key":"B26","doi-asserted-by":"publisher","first-page":"03946320241305270","DOI":"10.1177\/03946320241305270","article-title":"A new way of the Coombs test using flow cytometry-based assay to assess erythrocytes-bound IgG antibodies in the human and rabbit model","volume":"39","author":"Ullah","year":"2025"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbaf007","article-title":"Analytical methods in studying cell force sensing: principles, current technologies and perspectives","volume":"12","author":"Liu","year":"2025","journal-title":"Regener Biomater"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1136\/postgradmedj-2016-134724","article-title":"Association of HLA-DQB1 polymorphisms with rheumatoid arthritis: a meta-analysis","volume":"93","author":"Wu","year":"2017"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-23311-2_33","article-title":"The major histocompatibility complex and reactive arthritis","author":"Naovarat","year":"2019"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/tme.12459","article-title":"HLA polymorphisms and risk of red blood cell alloimmunisation in polytransfused patients with sickle cell anaemia","volume":"27","author":"Rodrigues","year":"2017"},{"key":"B31","doi-asserted-by":"crossref","first-page":"100794","DOI":"10.1016\/j.blre.2020.100794","article-title":"Back to base pairs: What is the genetic risk for red bloodcell alloimmunization?","volume":"48","author":"Gerritsma","year":"2021","journal-title":"Blood reviews"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-13-s1-o75","article-title":"HLA-DRB1* 11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis","volume":"112","author":"Ombrello","year":"2015"},{"key":"B33","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1177\/0961203318759200","article-title":"The influence of functional polymorphic positions of HLA-DR\u03b21 molecules on risk for South Indian systemic lupus erythematosus patients","volume":"27","author":"Katkam","year":"2018"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2016.11.005","article-title":"The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura","volume":"78","author":"Sinkovits","year":"2017"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70628","article-title":"Lymphoplasmapheresis for steroid\u2010refractory neuromyelitis optica spectrum disorder: a real\u2010world multicenter study in China","volume":"31","author":"Zeng","year":"2025","journal-title":"CNS Neurosci Ther"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-025-06288-z","article-title":"Association between HLA-DRB1* 04, HLA-DQB1* 03, and HLA-DQB1* 06 with alloimmunization in transfusion-dependent patients with thalassemia: the first case-control study in Iran","volume":"104","author":"Kargar","year":"2025","journal-title":"Ann Hematol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.46701\/apjbg.20170217023","article-title":"Association of HLA-DRB1 and HLA-DQB1 alleles with red blood cell auto-immunization in the Chinese population","volume":"1","author":"Lin","year":"2021","journal-title":"Blood&Genomics"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2016.09.009","article-title":"HLA class II regulation of immune response in sickle cell disease patients: susceptibility to red blood cell alloimmunization (systematic review and meta\u2010analysis)","volume":"117","author":"Wong","year":"2022","journal-title":"Vox Sang"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2022.2147801","article-title":"HLA-DQ genotype distribution and risk evaluation of celiac disease in Northwest China","volume":"58","author":"Shi","year":"2023","journal-title":"Scandinavian J Gastroenterol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/vox.13632","article-title":"Impact of human leucocyte antigen class II polymorphism on anti\u2010red blood cell antibody development: correlations and indications","volume":"119","author":"Milosavi\u0107","year":"2024","journal-title":"Vox Sang"}],"updated-by":[{"DOI":"10.3389\/fimmu.2026.1950557","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000}},{"DOI":"10.3389\/fimmu.2026.1950557","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1743789\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:55:19Z","timestamp":1792421719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1743789\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":40,"alternative-id":["10.3389\/fimmu.2026.1743789"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1743789","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"1743789"}}