Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy
Abstract: Immune aplastic anemia (iAA) frequently results in transfusion dependence on platelets and packed red blood cells, increasing the risk for complications. The most common immune-mediated cause for platelet-transfusion refractoriness is alloimmunization with HLA antibody (Ab) to nonself clas...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925001612 |
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| author | Jibran Durrani Leonard N. Chen Ruba N. Shalhoub Valentina Baez Joshua Glass Nu Ri Cha Xiaoyang Ma Zhijie Wu Shouguo Gao Jennifer Lotter Olga Rios Colin O. Wu Willy A. Flegel Neal S. Young Emma M. Groarke Bhavisha A. Patel |
| author_facet | Jibran Durrani Leonard N. Chen Ruba N. Shalhoub Valentina Baez Joshua Glass Nu Ri Cha Xiaoyang Ma Zhijie Wu Shouguo Gao Jennifer Lotter Olga Rios Colin O. Wu Willy A. Flegel Neal S. Young Emma M. Groarke Bhavisha A. Patel |
| author_sort | Jibran Durrani |
| collection | DOAJ |
| description | Abstract: Immune aplastic anemia (iAA) frequently results in transfusion dependence on platelets and packed red blood cells, increasing the risk for complications. The most common immune-mediated cause for platelet-transfusion refractoriness is alloimmunization with HLA antibody (Ab) to nonself class I antigens. The clinical impact of the HLA alloimmunization has not been well studied in patients with iAA. We investigated the clinical relevance of HLA alloimmunization in our large cohort of patients with iAA from 5 prospective trials and correlated with disease outcomes. Of 444 patients with severe AA treated with immunosuppressive therapy (IST), 99 (22%) had HLA alloimmunization. The presence of HLA Ab was associated with shorter overall survival, reduced responses to IST and higher risk of clonal evolution. Our data suggest that HLA alloimmunization is a marker of disease outcome. Furthermore, using single-cell RNA sequencing, we show enhanced activation of both complement-mediated pathways and the adaptive immune system in alloimmunized patients, indicating an interconnection between immune compartments. |
| format | Article |
| id | doaj-art-cc2be64b50eb4caea2b273e4c8a526fb |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-cc2be64b50eb4caea2b273e4c8a526fb2025-08-20T03:12:05ZengElsevierBlood Advances2473-95292025-06-019112639265010.1182/bloodadvances.2024015301Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapyJibran Durrani0Leonard N. Chen1Ruba N. Shalhoub2Valentina Baez3Joshua Glass4Nu Ri Cha5Xiaoyang Ma6Zhijie Wu7Shouguo Gao8Jennifer Lotter9Olga Rios10Colin O. Wu11Willy A. Flegel12Neal S. Young13Emma M. Groarke14Bhavisha A. Patel15Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FLBlood Services Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MDOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDLaboratory Services Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Division of Hematology, Cancer and Blood Disorders Center, Children’s National Hospital, Washington, DCLaboratory Services Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MDOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDLaboratory Services Section, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Correspondence: Bhavisha A. Patel, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Room 3-5140, Bethesda, MD 20892;Abstract: Immune aplastic anemia (iAA) frequently results in transfusion dependence on platelets and packed red blood cells, increasing the risk for complications. The most common immune-mediated cause for platelet-transfusion refractoriness is alloimmunization with HLA antibody (Ab) to nonself class I antigens. The clinical impact of the HLA alloimmunization has not been well studied in patients with iAA. We investigated the clinical relevance of HLA alloimmunization in our large cohort of patients with iAA from 5 prospective trials and correlated with disease outcomes. Of 444 patients with severe AA treated with immunosuppressive therapy (IST), 99 (22%) had HLA alloimmunization. The presence of HLA Ab was associated with shorter overall survival, reduced responses to IST and higher risk of clonal evolution. Our data suggest that HLA alloimmunization is a marker of disease outcome. Furthermore, using single-cell RNA sequencing, we show enhanced activation of both complement-mediated pathways and the adaptive immune system in alloimmunized patients, indicating an interconnection between immune compartments.http://www.sciencedirect.com/science/article/pii/S2473952925001612 |
| spellingShingle | Jibran Durrani Leonard N. Chen Ruba N. Shalhoub Valentina Baez Joshua Glass Nu Ri Cha Xiaoyang Ma Zhijie Wu Shouguo Gao Jennifer Lotter Olga Rios Colin O. Wu Willy A. Flegel Neal S. Young Emma M. Groarke Bhavisha A. Patel Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy Blood Advances |
| title | Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy |
| title_full | Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy |
| title_fullStr | Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy |
| title_full_unstemmed | Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy |
| title_short | Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy |
| title_sort | impact of hla alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925001612 |
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