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Exploring the Potential of Population-Optimized Red Blood Cell Antigens and Platelet HLA Typing for Homologous Blood Transfusion Detection in Japanese Athletes.

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Title: Exploring the Potential of Population-Optimized Red Blood Cell Antigens and Platelet HLA Typing for Homologous Blood Transfusion Detection in Japanese Athletes.
Authors: Momobayashi A; Anti-Doping Laboratory, LSI Medience Corporation, Tokyo, Japan., Okano M; Anti-Doping Laboratory, LSI Medience Corporation, Tokyo, Japan.
Source: Drug testing and analysis [Drug Test Anal] 2026 Sep; Vol. 18 (9), pp. 1186-1197. Date of Electronic Publication: 2026 Jun 23.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: John Wiley & Sons Country of Publication: England NLM ID: 101483449 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1942-7611 (Electronic) Linking ISSN: 19427603 NLM ISO Abbreviation: Drug Test Anal Subsets: MEDLINE
Imprint Name(s): Original Publication: Chichester, UK : John Wiley & Sons
MeSH Terms: Blood Platelets*/immunology , Doping in Sports*/prevention & control , Erythrocytes*/immunology , Erythrocytes*/chemistry , Histocompatibility Testing*/methods , HLA Antigens*/blood , HLA Antigens*/analysis, Flow Cytometry/methods ; Humans ; Athletes ; Blood Transfusion ; Japan ; East Asian People
Abstract: Homologous blood transfusion (HBT) doping, using donor red blood cells (RBCs) to enhance oxygen capacity, remains a persistent challenge for doping control laboratories, especially in specific populations. Current RBC antigen-based flow cytometric detection (double population, DP) has limited sensitivity in genetically homogeneous populations due to common phenotypic overlap. This study aimed to enhance HBT detection by optimizing population-specific RBC antigen panels and incorporating complementary platelet-derived human leukocyte antigen (HLA) markers. Based on antigen-negative frequency, M, N, and Leb antigens were evaluated as candidate markers for improved discrimination in the Japanese population. In simulated HBT samples with a 5% mixing ratio, N antigen showed a clearly separated bimodal distribution, indicating strong potential for DP detection. Although Leb antigen showed unclear DP, M antigen displayed uniformly high expression, useful for distinguishing expressing populations. In addition, platelet HLA analysis, especially targeting HLA-A24, enabled detection of donor-derived components even with identical RBC antigen phenotypes. Mixed samples containing as low as 1%-5% donor cells produced visually detectable DP signals in the platelet gate. In conclusion, integrating a race-tailored RBC antigen panel with complementary platelet HLA monitoring may provide a potentially improved framework for HBT detection, particularly in ethnically homogeneous populations like Japan. The optimal antigen panel is highly population-specific due to genetic variations, requiring adaptation for other diverse ethnic groups. Future cohort studies are warranted to validate this dual approach and refine detection sensitivity.
(© 2026 John Wiley & Sons Ltd.)
References: Haematologica. 2003 Nov;88(11):1284-95. (PMID: 14607758)
Forensic Sci Int. 2008 Jul 18;179(1):23-33. (PMID: 18514452)
Drug Test Anal. 2022 Nov;14(11-12):1836-1852. (PMID: 36208085)
Transfusion. 1990 Feb;30(2):117-25. (PMID: 2305440)
Front Sports Act Living. 2022 Feb 10;4:808449. (PMID: 35224486)
Vox Sang. 1987;53(1):23-5. (PMID: 3660767)
Drug Test Anal. 2023 Mar;15(3):292-298. (PMID: 36346023)
Cancers (Basel). 2021 Jun 29;13(13):. (PMID: 34209910)
Transfus Apher Sci. 2001 Jun;24(3):279-86. (PMID: 11791703)
PLoS One. 2018 Apr 12;13(4):e0195778. (PMID: 29649328)
ISRN Hematol. 2014 Mar 25;2014:176060. (PMID: 25006472)
Int J Sports Med. 2007 Aug;28(8):633-7. (PMID: 17614019)
Oman Med J. 2019 Nov;34(6):496-503. (PMID: 31745413)
Am J Hum Genet. 1976 Jul;28(4):390-9. (PMID: 941906)
Biol Blood Marrow Transplant. 2008 Jun;14(6):693-701. (PMID: 18489995)
Drug Test Anal. 2025 Feb;17(2):311-320. (PMID: 38726802)
Tissue Antigens. 2015 Apr;85(4):252-9. (PMID: 25789826)
Contributed Indexing: Keywords: HLA; doping; flow cytometry; homologous blood transfusion; red blood cell
Substance Nomenclature: 0 (HLA Antigens)
Entry Date(s): Date Created: 20260624 Date Completed: 20260901 Latest Revision: 20260930
Update Code: 20260930
PubMed Central ID: PMC13532906
DOI: 10.1002/dta.70108
PMID: 42338234
Database: MEDLINE
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  Data: Exploring the Potential of Population-Optimized Red Blood Cell Antigens and Platelet HLA Typing for Homologous Blood Transfusion Detection in Japanese Athletes.
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  Data: <searchLink fieldCode="AU" term="%22Momobayashi+A%22">Momobayashi A</searchLink>; Anti-Doping Laboratory, LSI Medience Corporation, Tokyo, Japan.<br /><searchLink fieldCode="AU" term="%22Okano+M%22">Okano M</searchLink>; Anti-Doping Laboratory, LSI Medience Corporation, Tokyo, Japan.
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  Data: <searchLink fieldCode="JN" term="%22101483449%22">Drug testing and analysis</searchLink> [Drug Test Anal] 2026 Sep; Vol. 18 (9), pp. 1186-1197. <i>Date of Electronic Publication: </i>2026 Jun 23.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22John+Wiley+%26+Sons%22">John Wiley & Sons </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>101483449 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1942-7611 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2219427603%22">19427603 </searchLink><i>NLM ISO Abbreviation: </i>Drug Test Anal <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Chichester, UK : John Wiley & Sons
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  Data: <searchLink fieldCode="MM" term="%22Blood+Platelets%22">Blood Platelets*</searchLink>/<searchLink fieldCode="MM" term="%22Blood+Platelets+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Doping+in+Sports%22">Doping in Sports*</searchLink>/<searchLink fieldCode="MM" term="%22Doping+in+Sports+prevention+%26+control%22">prevention & control</searchLink> <br /><searchLink fieldCode="MM" term="%22Erythrocytes%22">Erythrocytes*</searchLink>/<searchLink fieldCode="MM" term="%22Erythrocytes+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Erythrocytes%22">Erythrocytes*</searchLink>/<searchLink fieldCode="MM" term="%22Erythrocytes+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Histocompatibility+Testing%22">Histocompatibility Testing*</searchLink>/<searchLink fieldCode="MM" term="%22Histocompatibility+Testing+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22HLA+Antigens%22">HLA Antigens*</searchLink>/<searchLink fieldCode="MM" term="%22HLA+Antigens+blood%22">blood</searchLink> <br /><searchLink fieldCode="MM" term="%22HLA+Antigens%22">HLA Antigens*</searchLink>/<searchLink fieldCode="MM" term="%22HLA+Antigens+analysis%22">analysis</searchLink><br /><searchLink fieldCode="MH" term="%22Flow+Cytometry%22">Flow Cytometry</searchLink>/<searchLink fieldCode="MH" term="%22Flow+Cytometry+methods%22">methods</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Athletes%22">Athletes</searchLink> ; <searchLink fieldCode="MH" term="%22Blood+Transfusion%22">Blood Transfusion</searchLink> ; <searchLink fieldCode="MH" term="%22Japan%22">Japan</searchLink> ; <searchLink fieldCode="MH" term="%22East+Asian+People%22">East Asian People</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Homologous blood transfusion (HBT) doping, using donor red blood cells (RBCs) to enhance oxygen capacity, remains a persistent challenge for doping control laboratories, especially in specific populations. Current RBC antigen-based flow cytometric detection (double population, DP) has limited sensitivity in genetically homogeneous populations due to common phenotypic overlap. This study aimed to enhance HBT detection by optimizing population-specific RBC antigen panels and incorporating complementary platelet-derived human leukocyte antigen (HLA) markers. Based on antigen-negative frequency, M, N, and Le<superscript>b</superscript> antigens were evaluated as candidate markers for improved discrimination in the Japanese population. In simulated HBT samples with a 5% mixing ratio, N antigen showed a clearly separated bimodal distribution, indicating strong potential for DP detection. Although Le<superscript>b</superscript> antigen showed unclear DP, M antigen displayed uniformly high expression, useful for distinguishing expressing populations. In addition, platelet HLA analysis, especially targeting HLA-A24, enabled detection of donor-derived components even with identical RBC antigen phenotypes. Mixed samples containing as low as 1%-5% donor cells produced visually detectable DP signals in the platelet gate. In conclusion, integrating a race-tailored RBC antigen panel with complementary platelet HLA monitoring may provide a potentially improved framework for HBT detection, particularly in ethnically homogeneous populations like Japan. The optimal antigen panel is highly population-specific due to genetic variations, requiring adaptation for other diverse ethnic groups. Future cohort studies are warranted to validate this dual approach and refine detection sensitivity.<br /> (© 2026 John Wiley & Sons Ltd.)
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Haematologica. 2003 Nov;88(11):1284-95. (PMID: <searchLink fieldCode="PM" term="%2214607758%22">14607758)</searchLink><br />Forensic Sci Int. 2008 Jul 18;179(1):23-33. (PMID: <searchLink fieldCode="PM" term="%2218514452%22">18514452)</searchLink><br />Drug Test Anal. 2022 Nov;14(11-12):1836-1852. (PMID: <searchLink fieldCode="PM" term="%2236208085%22">36208085)</searchLink><br />Transfusion. 1990 Feb;30(2):117-25. (PMID: <searchLink fieldCode="PM" term="%222305440%22">2305440)</searchLink><br />Front Sports Act Living. 2022 Feb 10;4:808449. (PMID: <searchLink fieldCode="PM" term="%2235224486%22">35224486)</searchLink><br />Vox Sang. 1987;53(1):23-5. (PMID: <searchLink fieldCode="PM" term="%223660767%22">3660767)</searchLink><br />Drug Test Anal. 2023 Mar;15(3):292-298. (PMID: <searchLink fieldCode="PM" term="%2236346023%22">36346023)</searchLink><br />Cancers (Basel). 2021 Jun 29;13(13):. (PMID: <searchLink fieldCode="PM" term="%2234209910%22">34209910)</searchLink><br />Transfus Apher Sci. 2001 Jun;24(3):279-86. (PMID: <searchLink fieldCode="PM" term="%2211791703%22">11791703)</searchLink><br />PLoS One. 2018 Apr 12;13(4):e0195778. (PMID: <searchLink fieldCode="PM" term="%2229649328%22">29649328)</searchLink><br />ISRN Hematol. 2014 Mar 25;2014:176060. (PMID: <searchLink fieldCode="PM" term="%2225006472%22">25006472)</searchLink><br />Int J Sports Med. 2007 Aug;28(8):633-7. (PMID: <searchLink fieldCode="PM" term="%2217614019%22">17614019)</searchLink><br />Oman Med J. 2019 Nov;34(6):496-503. (PMID: <searchLink fieldCode="PM" term="%2231745413%22">31745413)</searchLink><br />Am J Hum Genet. 1976 Jul;28(4):390-9. (PMID: <searchLink fieldCode="PM" term="%22941906%22">941906)</searchLink><br />Biol Blood Marrow Transplant. 2008 Jun;14(6):693-701. (PMID: <searchLink fieldCode="PM" term="%2218489995%22">18489995)</searchLink><br />Drug Test Anal. 2025 Feb;17(2):311-320. (PMID: <searchLink fieldCode="PM" term="%2238726802%22">38726802)</searchLink><br />Tissue Antigens. 2015 Apr;85(4):252-9. (PMID: <searchLink fieldCode="PM" term="%2225789826%22">25789826)</searchLink>
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  Data: <i>Keywords: </i>HLA; doping; flow cytometry; homologous blood transfusion; red blood cell
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  Data: <i>Date Created: </i>20260624 <i>Date Completed: </i>20260901 <i>Latest Revision: </i>20260930
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  Data: 20260930
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  Data: 10.1002/dta.70108
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        Value: 10.1002/dta.70108
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      – Code: eng
        Text: English
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        StartPage: 1186
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      – SubjectFull: Flow Cytometry methods
        Type: general
      – SubjectFull: Humans
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      – SubjectFull: Athletes
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      – SubjectFull: HLA Antigens blood
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      – SubjectFull: HLA Antigens analysis
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      – TitleFull: Exploring the Potential of Population-Optimized Red Blood Cell Antigens and Platelet HLA Typing for Homologous Blood Transfusion Detection in Japanese Athletes.
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              Text: 2026 Sep
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