title: Platelets made HLA deficient by acid treatment aggregate normally and escape destruction by complement and phagocytes in the presence of HLA antibodies.
abstract: BACKGROUND
  The presence of antibodies against HLA Class I can lead to platelet (PLT) transfusion refractoriness, that is, the repeated failure to achieve adequate posttransfusion PLT count increments. PLT refractoriness can be overcome by transfusion of HLA-matched donor PLTs. A different approach is to remove HLA from the PLT surface using low pH. Previous case studies using HLA-stripped PLTs showed encouraging but inconsistent results and lacked information on the biologic effects of acid treatment on PLT function as well as sensitivity to PLT destruction in the presence of HLA antibodies.
  
  
  METHODS
  PLTs prepared from buffy coats were stripped from HLA Class I using a brief incubation at pH 2.9. Kinetics of acid stripping, viability, phenotypic alterations, and sensitivity to complement-mediated lysis and phagocytosis were determined by flow cytometry. Functional potential was evaluated using a multiplate analyzer.
  
  
  RESULTS
  Acid-treated PLTs were viable, upregulated activation markers normally and aggregated to a similar extent as untreated PLTs in response to stimulation with three natural agonists. Acid treatment removed 70% to 90% of HLA Class I complexes from the PLT surface, which led to complete protection from HLA antibody-mediated complement lysis and reduced monocyte-mediated phagocytosis in the presence of anti-HLA in vitro.
  
  
  CONCLUSIONS
  Our study fills an important knowledge gap in how acid treatment affects PLT function and interactions with immune cells, paving the way for controlled clinical trials to evaluate acid-treated PLTs as an alternative to HLA-matched donors in PLT refractoriness.
authors.affiliation: Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.|Clinic for Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Stephan
authors.initials: S
authors.lastname: Meinke
authors.affiliation: Clinic for Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Sandgren
authors.affiliation: Clinic for Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anette
authors.initials: A
authors.lastname: Mörtberg
authors.affiliation: Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.|Clinic for Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Karlström
authors.affiliation: Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nadir
authors.initials: N
authors.lastname: Kadri
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Clinic for Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Wikman
authors.affiliation: Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.|Clinic for Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Höglund
mesh_terms: D001792:Blood Platelets / Q000737:chemistry* / Q000166:cytology; D019343:Citric Acid / Q000737:chemistry*; D003165:Complement System Proteins / Q000737:chemistry*; D005260:Female; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010586:Phagocytes; D010974:Platelet Aggregation
chemical_list: D006680:HLA Antigens; D019343:Citric Acid; D003165:Complement System Proteins