HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.
Identifieur interne : 003224 ( PubMed/Corpus ); précédent : 003223; suivant : 003225HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.
Auteurs : Effie W. Petersdorf ; Theodore A. Gooley ; Mari Malkki ; Andrea P. Bacigalupo ; Anne Cesbron ; Ernette Du Toit ; Gerhard Ehninger ; Torstein Egeland ; Gottfried F. Fischer ; Thibaut Gervais ; Michael D. Haagenson ; Mary M. Horowitz ; Katharine Hsu ; Pavel Jindra ; Alejandro Madrigal ; Machteld Oudshoorn ; Olle Ringdén ; Marlis L. Schroeder ; Stephen R. Spellman ; Jean-Marie Tiercy ; Andrea Velardi ; Campbell S. Witt ; Colm O'Huigin ; Richard Apps ; Mary CarringtonSource :
- Blood [ 1528-0020 ] ; 2014.
English descriptors
- KwdEn :
- Adolescent, Adult, Aged, Alleles, Female, Graft vs Host Disease, HLA-C Antigens (metabolism), Hematopoietic Stem Cell Transplantation, Histocompatibility (immunology), Humans, Leukemia (immunology), Leukemia (therapy), Male, Middle Aged, Multivariate Analysis, Myelodysplastic Syndromes (immunology), Myelodysplastic Syndromes (therapy), Retrospective Studies, Treatment Outcome, Unrelated Donors, Young Adult.
- MESH :
- chemical , metabolism : HLA-C Antigens.
- immunology : Histocompatibility, Leukemia, Myelodysplastic Syndromes.
- therapy : Leukemia, Myelodysplastic Syndromes.
- Adolescent, Adult, Aged, Alleles, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Multivariate Analysis, Retrospective Studies, Treatment Outcome, Unrelated Donors, Young Adult.
Abstract
Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease.
DOI: 10.1182/blood-2014-09-599969
PubMed: 25323824
Links to Exploration step
pubmed:25323824Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.</title><author><name sortKey="Petersdorf, Effie W" sort="Petersdorf, Effie W" uniqKey="Petersdorf E" first="Effie W" last="Petersdorf">Effie W. Petersdorf</name><affiliation><nlm:affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, University of Washington School of Medicine, Seattle, WA;</nlm:affiliation></affiliation></author><author><name sortKey="Gooley, Theodore A" sort="Gooley, Theodore A" uniqKey="Gooley T" first="Theodore A" last="Gooley">Theodore A. Gooley</name><affiliation><nlm:affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA;</nlm:affiliation></affiliation></author><author><name sortKey="Malkki, Mari" sort="Malkki, Mari" uniqKey="Malkki M" first="Mari" last="Malkki">Mari Malkki</name><affiliation><nlm:affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA;</nlm:affiliation></affiliation></author><author><name sortKey="Bacigalupo, Andrea P" sort="Bacigalupo, Andrea P" uniqKey="Bacigalupo A" first="Andrea P" last="Bacigalupo">Andrea P. Bacigalupo</name><affiliation><nlm:affiliation>Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino, Genova, Italy;</nlm:affiliation></affiliation></author><author><name sortKey="Cesbron, Anne" sort="Cesbron, Anne" uniqKey="Cesbron A" first="Anne" last="Cesbron">Anne Cesbron</name><affiliation><nlm:affiliation>Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang Pays de Loire, Nantes, France;</nlm:affiliation></affiliation></author><author><name sortKey="Du Toit, Ernette" sort="Du Toit, Ernette" uniqKey="Du Toit E" first="Ernette" last="Du Toit">Ernette Du Toit</name><affiliation><nlm:affiliation>University of Cape Town, Cape Town and South African Bone Marrow Registry, Cape Town, South Africa;</nlm:affiliation></affiliation></author><author><name sortKey="Ehninger, Gerhard" sort="Ehninger, Gerhard" uniqKey="Ehninger G" first="Gerhard" last="Ehninger">Gerhard Ehninger</name><affiliation><nlm:affiliation>Universitätsklinikum Carl Gustav Carus, Dresden, Germany;</nlm:affiliation></affiliation></author><author><name sortKey="Egeland, Torstein" sort="Egeland, Torstein" uniqKey="Egeland T" first="Torstein" last="Egeland">Torstein Egeland</name><affiliation><nlm:affiliation>Department of Immunology, Oslo University Hospital, Oslo, Norway;</nlm:affiliation></affiliation></author><author><name sortKey="Fischer, Gottfried F" sort="Fischer, Gottfried F" uniqKey="Fischer G" first="Gottfried F" last="Fischer">Gottfried F. Fischer</name><affiliation><nlm:affiliation>Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria;</nlm:affiliation></affiliation></author><author><name sortKey="Gervais, Thibaut" sort="Gervais, Thibaut" uniqKey="Gervais T" first="Thibaut" last="Gervais">Thibaut Gervais</name><affiliation><nlm:affiliation>Cliniques St. Luc, Université Catholique de Louvain, Brussels, Belgium;</nlm:affiliation></affiliation></author><author><name sortKey="Haagenson, Michael D" sort="Haagenson, Michael D" uniqKey="Haagenson M" first="Michael D" last="Haagenson">Michael D. Haagenson</name><affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research, Minneapolis, MN;</nlm:affiliation></affiliation></author><author><name sortKey="Horowitz, Mary M" sort="Horowitz, Mary M" uniqKey="Horowitz M" first="Mary M" last="Horowitz">Mary M. Horowitz</name><affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI;</nlm:affiliation></affiliation></author><author><name sortKey="Hsu, Katharine" sort="Hsu, Katharine" uniqKey="Hsu K" first="Katharine" last="Hsu">Katharine Hsu</name><affiliation><nlm:affiliation>Memorial Sloan-Kettering Cancer Center, New York, NY;</nlm:affiliation></affiliation></author><author><name sortKey="Jindra, Pavel" sort="Jindra, Pavel" uniqKey="Jindra P" first="Pavel" last="Jindra">Pavel Jindra</name><affiliation><nlm:affiliation>University Hospital, Pilsen, Czech Republic;</nlm:affiliation></affiliation></author><author><name sortKey="Madrigal, Alejandro" sort="Madrigal, Alejandro" uniqKey="Madrigal A" first="Alejandro" last="Madrigal">Alejandro Madrigal</name><affiliation><nlm:affiliation>Anthony Nolan Research Institute, The Royal Free Hampstead NHS Trust, London, United Kingdom;</nlm:affiliation></affiliation></author><author><name sortKey="Oudshoorn, Machteld" sort="Oudshoorn, Machteld" uniqKey="Oudshoorn M" first="Machteld" last="Oudshoorn">Machteld Oudshoorn</name><affiliation><nlm:affiliation>Leiden University Medical Center and Europdonor Foundation, Leiden, The Netherlands;</nlm:affiliation></affiliation></author><author><name sortKey="Ringden, Olle" sort="Ringden, Olle" uniqKey="Ringden O" first="Olle" last="Ringdén">Olle Ringdén</name><affiliation><nlm:affiliation>Division of Therapeutic Immunology, Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden;</nlm:affiliation></affiliation></author><author><name sortKey="Schroeder, Marlis L" sort="Schroeder, Marlis L" uniqKey="Schroeder M" first="Marlis L" last="Schroeder">Marlis L. Schroeder</name><affiliation><nlm:affiliation>Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada;</nlm:affiliation></affiliation></author><author><name sortKey="Spellman, Stephen R" sort="Spellman, Stephen R" uniqKey="Spellman S" first="Stephen R" last="Spellman">Stephen R. Spellman</name><affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research, Minneapolis, MN;</nlm:affiliation></affiliation></author><author><name sortKey="Tiercy, Jean Marie" sort="Tiercy, Jean Marie" uniqKey="Tiercy J" first="Jean-Marie" last="Tiercy">Jean-Marie Tiercy</name><affiliation><nlm:affiliation>National Reference Laboratory for Histocompatibility, Department of Genetics and Laboratory Medicine, University Hospital Geneva, Geneva, Switzerland;</nlm:affiliation></affiliation></author><author><name sortKey="Velardi, Andrea" sort="Velardi, Andrea" uniqKey="Velardi A" first="Andrea" last="Velardi">Andrea Velardi</name><affiliation><nlm:affiliation>European Group for Blood and Marrow Transplantation and University of Perugia, Perugia, Italy;</nlm:affiliation></affiliation></author><author><name sortKey="Witt, Campbell S" sort="Witt, Campbell S" uniqKey="Witt C" first="Campbell S" last="Witt">Campbell S. Witt</name><affiliation><nlm:affiliation>Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia;</nlm:affiliation></affiliation></author><author><name sortKey="O Huigin, Colm" sort="O Huigin, Colm" uniqKey="O Huigin C" first="Colm" last="O'Huigin">Colm O'Huigin</name><affiliation><nlm:affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and.</nlm:affiliation></affiliation></author><author><name sortKey="Apps, Richard" sort="Apps, Richard" uniqKey="Apps R" first="Richard" last="Apps">Richard Apps</name><affiliation><nlm:affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and Ragon Institute of the Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Carrington, Mary" sort="Carrington, Mary" uniqKey="Carrington M" first="Mary" last="Carrington">Mary Carrington</name><affiliation><nlm:affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and Ragon Institute of the Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25323824</idno><idno type="pmid">25323824</idno><idno type="doi">10.1182/blood-2014-09-599969</idno><idno type="wicri:Area/PubMed/Corpus">003224</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003224</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.</title><author><name sortKey="Petersdorf, Effie W" sort="Petersdorf, Effie W" uniqKey="Petersdorf E" first="Effie W" last="Petersdorf">Effie W. Petersdorf</name><affiliation><nlm:affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, University of Washington School of Medicine, Seattle, WA;</nlm:affiliation></affiliation></author><author><name sortKey="Gooley, Theodore A" sort="Gooley, Theodore A" uniqKey="Gooley T" first="Theodore A" last="Gooley">Theodore A. Gooley</name><affiliation><nlm:affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA;</nlm:affiliation></affiliation></author><author><name sortKey="Malkki, Mari" sort="Malkki, Mari" uniqKey="Malkki M" first="Mari" last="Malkki">Mari Malkki</name><affiliation><nlm:affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA;</nlm:affiliation></affiliation></author><author><name sortKey="Bacigalupo, Andrea P" sort="Bacigalupo, Andrea P" uniqKey="Bacigalupo A" first="Andrea P" last="Bacigalupo">Andrea P. Bacigalupo</name><affiliation><nlm:affiliation>Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino, Genova, Italy;</nlm:affiliation></affiliation></author><author><name sortKey="Cesbron, Anne" sort="Cesbron, Anne" uniqKey="Cesbron A" first="Anne" last="Cesbron">Anne Cesbron</name><affiliation><nlm:affiliation>Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang Pays de Loire, Nantes, France;</nlm:affiliation></affiliation></author><author><name sortKey="Du Toit, Ernette" sort="Du Toit, Ernette" uniqKey="Du Toit E" first="Ernette" last="Du Toit">Ernette Du Toit</name><affiliation><nlm:affiliation>University of Cape Town, Cape Town and South African Bone Marrow Registry, Cape Town, South Africa;</nlm:affiliation></affiliation></author><author><name sortKey="Ehninger, Gerhard" sort="Ehninger, Gerhard" uniqKey="Ehninger G" first="Gerhard" last="Ehninger">Gerhard Ehninger</name><affiliation><nlm:affiliation>Universitätsklinikum Carl Gustav Carus, Dresden, Germany;</nlm:affiliation></affiliation></author><author><name sortKey="Egeland, Torstein" sort="Egeland, Torstein" uniqKey="Egeland T" first="Torstein" last="Egeland">Torstein Egeland</name><affiliation><nlm:affiliation>Department of Immunology, Oslo University Hospital, Oslo, Norway;</nlm:affiliation></affiliation></author><author><name sortKey="Fischer, Gottfried F" sort="Fischer, Gottfried F" uniqKey="Fischer G" first="Gottfried F" last="Fischer">Gottfried F. Fischer</name><affiliation><nlm:affiliation>Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria;</nlm:affiliation></affiliation></author><author><name sortKey="Gervais, Thibaut" sort="Gervais, Thibaut" uniqKey="Gervais T" first="Thibaut" last="Gervais">Thibaut Gervais</name><affiliation><nlm:affiliation>Cliniques St. Luc, Université Catholique de Louvain, Brussels, Belgium;</nlm:affiliation></affiliation></author><author><name sortKey="Haagenson, Michael D" sort="Haagenson, Michael D" uniqKey="Haagenson M" first="Michael D" last="Haagenson">Michael D. Haagenson</name><affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research, Minneapolis, MN;</nlm:affiliation></affiliation></author><author><name sortKey="Horowitz, Mary M" sort="Horowitz, Mary M" uniqKey="Horowitz M" first="Mary M" last="Horowitz">Mary M. Horowitz</name><affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI;</nlm:affiliation></affiliation></author><author><name sortKey="Hsu, Katharine" sort="Hsu, Katharine" uniqKey="Hsu K" first="Katharine" last="Hsu">Katharine Hsu</name><affiliation><nlm:affiliation>Memorial Sloan-Kettering Cancer Center, New York, NY;</nlm:affiliation></affiliation></author><author><name sortKey="Jindra, Pavel" sort="Jindra, Pavel" uniqKey="Jindra P" first="Pavel" last="Jindra">Pavel Jindra</name><affiliation><nlm:affiliation>University Hospital, Pilsen, Czech Republic;</nlm:affiliation></affiliation></author><author><name sortKey="Madrigal, Alejandro" sort="Madrigal, Alejandro" uniqKey="Madrigal A" first="Alejandro" last="Madrigal">Alejandro Madrigal</name><affiliation><nlm:affiliation>Anthony Nolan Research Institute, The Royal Free Hampstead NHS Trust, London, United Kingdom;</nlm:affiliation></affiliation></author><author><name sortKey="Oudshoorn, Machteld" sort="Oudshoorn, Machteld" uniqKey="Oudshoorn M" first="Machteld" last="Oudshoorn">Machteld Oudshoorn</name><affiliation><nlm:affiliation>Leiden University Medical Center and Europdonor Foundation, Leiden, The Netherlands;</nlm:affiliation></affiliation></author><author><name sortKey="Ringden, Olle" sort="Ringden, Olle" uniqKey="Ringden O" first="Olle" last="Ringdén">Olle Ringdén</name><affiliation><nlm:affiliation>Division of Therapeutic Immunology, Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden;</nlm:affiliation></affiliation></author><author><name sortKey="Schroeder, Marlis L" sort="Schroeder, Marlis L" uniqKey="Schroeder M" first="Marlis L" last="Schroeder">Marlis L. Schroeder</name><affiliation><nlm:affiliation>Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada;</nlm:affiliation></affiliation></author><author><name sortKey="Spellman, Stephen R" sort="Spellman, Stephen R" uniqKey="Spellman S" first="Stephen R" last="Spellman">Stephen R. Spellman</name><affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research, Minneapolis, MN;</nlm:affiliation></affiliation></author><author><name sortKey="Tiercy, Jean Marie" sort="Tiercy, Jean Marie" uniqKey="Tiercy J" first="Jean-Marie" last="Tiercy">Jean-Marie Tiercy</name><affiliation><nlm:affiliation>National Reference Laboratory for Histocompatibility, Department of Genetics and Laboratory Medicine, University Hospital Geneva, Geneva, Switzerland;</nlm:affiliation></affiliation></author><author><name sortKey="Velardi, Andrea" sort="Velardi, Andrea" uniqKey="Velardi A" first="Andrea" last="Velardi">Andrea Velardi</name><affiliation><nlm:affiliation>European Group for Blood and Marrow Transplantation and University of Perugia, Perugia, Italy;</nlm:affiliation></affiliation></author><author><name sortKey="Witt, Campbell S" sort="Witt, Campbell S" uniqKey="Witt C" first="Campbell S" last="Witt">Campbell S. Witt</name><affiliation><nlm:affiliation>Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia;</nlm:affiliation></affiliation></author><author><name sortKey="O Huigin, Colm" sort="O Huigin, Colm" uniqKey="O Huigin C" first="Colm" last="O'Huigin">Colm O'Huigin</name><affiliation><nlm:affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and.</nlm:affiliation></affiliation></author><author><name sortKey="Apps, Richard" sort="Apps, Richard" uniqKey="Apps R" first="Richard" last="Apps">Richard Apps</name><affiliation><nlm:affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and Ragon Institute of the Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Carrington, Mary" sort="Carrington, Mary" uniqKey="Carrington M" first="Mary" last="Carrington">Mary Carrington</name><affiliation><nlm:affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and Ragon Institute of the Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Blood</title><idno type="eISSN">1528-0020</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Alleles</term><term>Female</term><term>Graft vs Host Disease</term><term>HLA-C Antigens (metabolism)</term><term>Hematopoietic Stem Cell Transplantation</term><term>Histocompatibility (immunology)</term><term>Humans</term><term>Leukemia (immunology)</term><term>Leukemia (therapy)</term><term>Male</term><term>Middle Aged</term><term>Multivariate Analysis</term><term>Myelodysplastic Syndromes (immunology)</term><term>Myelodysplastic Syndromes (therapy)</term><term>Retrospective Studies</term><term>Treatment Outcome</term><term>Unrelated Donors</term><term>Young Adult</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HLA-C Antigens</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Histocompatibility</term><term>Leukemia</term><term>Myelodysplastic Syndromes</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Leukemia</term><term>Myelodysplastic Syndromes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Alleles</term><term>Female</term><term>Graft vs Host Disease</term><term>Hematopoietic Stem Cell Transplantation</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Multivariate Analysis</term><term>Retrospective Studies</term><term>Treatment Outcome</term><term>Unrelated Donors</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25323824</PMID><DateCreated><Year>2014</Year><Month>12</Month><Day>19</Day></DateCreated><DateCompleted><Year>2015</Year><Month>02</Month><Day>23</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>03</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1528-0020</ISSN><JournalIssue CitedMedium="Internet"><Volume>124</Volume><Issue>26</Issue><PubDate><Year>2014</Year><Month>Dec</Month><Day>18</Day></PubDate></JournalIssue><Title>Blood</Title><ISOAbbreviation>Blood</ISOAbbreviation></Journal><ArticleTitle>HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.</ArticleTitle><Pagination><MedlinePgn>3996-4003</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1182/blood-2014-09-599969</ELocationID><Abstract><AbstractText>Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease.</AbstractText><CopyrightInformation>© 2014 by The American Society of Hematology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Petersdorf</LastName><ForeName>Effie W</ForeName><Initials>EW</Initials><AffiliationInfo><Affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, University of Washington School of Medicine, Seattle, WA;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gooley</LastName><ForeName>Theodore A</ForeName><Initials>TA</Initials><AffiliationInfo><Affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malkki</LastName><ForeName>Mari</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bacigalupo</LastName><ForeName>Andrea P</ForeName><Initials>AP</Initials><AffiliationInfo><Affiliation>Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino, Genova, Italy;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cesbron</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang Pays de Loire, Nantes, France;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Du Toit</LastName><ForeName>Ernette</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>University of Cape Town, Cape Town and South African Bone Marrow Registry, Cape Town, South Africa;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ehninger</LastName><ForeName>Gerhard</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Universitätsklinikum Carl Gustav Carus, Dresden, Germany;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Egeland</LastName><ForeName>Torstein</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Immunology, Oslo University Hospital, Oslo, Norway;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fischer</LastName><ForeName>Gottfried F</ForeName><Initials>GF</Initials><AffiliationInfo><Affiliation>Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gervais</LastName><ForeName>Thibaut</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Cliniques St. Luc, Université Catholique de Louvain, Brussels, Belgium;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haagenson</LastName><ForeName>Michael D</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>Center for International Blood and Marrow Transplant Research, Minneapolis, MN;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Horowitz</LastName><ForeName>Mary M</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hsu</LastName><ForeName>Katharine</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Memorial Sloan-Kettering Cancer Center, New York, NY;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jindra</LastName><ForeName>Pavel</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>University Hospital, Pilsen, Czech Republic;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Madrigal</LastName><ForeName>Alejandro</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Anthony Nolan Research Institute, The Royal Free Hampstead NHS Trust, London, United Kingdom;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oudshoorn</LastName><ForeName>Machteld</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Leiden University Medical Center and Europdonor Foundation, Leiden, The Netherlands;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ringdén</LastName><ForeName>Olle</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Division of Therapeutic Immunology, Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schroeder</LastName><ForeName>Marlis L</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spellman</LastName><ForeName>Stephen R</ForeName><Initials>SR</Initials><AffiliationInfo><Affiliation>Center for International Blood and Marrow Transplant Research, Minneapolis, MN;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tiercy</LastName><ForeName>Jean-Marie</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>National Reference Laboratory for Histocompatibility, Department of Genetics and Laboratory Medicine, University Hospital Geneva, Geneva, Switzerland;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Velardi</LastName><ForeName>Andrea</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>European Group for Blood and Marrow Transplantation and University of Perugia, Perugia, Italy;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Witt</LastName><ForeName>Campbell S</ForeName><Initials>CS</Initials><AffiliationInfo><Affiliation>Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>O'Huigin</LastName><ForeName>Colm</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Apps</LastName><ForeName>Richard</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and Ragon Institute of the Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carrington</LastName><ForeName>Mary</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Cancer and Inflammation Program, SAIC Frederick, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD; and Ragon Institute of the Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>International Histocompatibility Working Group in Hematopoietic Cell Transplantation</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>5U01HL069294</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>CA18029</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 CA018029</GrantID><Acronym>CA</Acronym><Agency>NCI 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