PMID- 33580979 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20210719 IS - 1537-2995 (Electronic) IS - 0041-1132 (Linking) VI - 61 IP - 4 DP - 2021 Apr TI - HLA class I depletion by citric acid, and irradiation of apheresis platelets for transfusion of refractory patients. PG - 1222-1234 LID - 10.1111/trf.16282 [doi] AB - BACKGROUND: Patients can form antibodies to foreign human leukocyte antigen (HLA) Class I antigens after exposure to allogeneic cells. These anti-HLA class I antibodies can bind transfused platelets (PLTs) and mediate their destruction, thus leading to PLT refractoriness. Patients with PLT refractoriness need HLA-matched PLTs, which require expensive HLA typing of donors, antibody analyses of patient sera and/or crossmatching. An alternative approach is to reduce PLT HLA Class I expression using a brief incubation in citric acid on ice at low pH. METHODS AND MATERIALS: Apheresis PLT concentrates were depleted of HLA Class I complexes by 5 minutes incubation in ice-cold citric acid, at pH 3.0. Surface expression of HLA Class I complexes, CD62P, CD63, phosphatidylserine, and complement factor C3c was analyzed by flow cytometry. PLT functionality was tested by thromboelastography (TEG). RESULTS: Acid treatment reduced the expression of HLA Class I complexes by 71% and potential for C3c binding by 11.5-fold compared to untreated PLTs. Acid-treated PLTs were significantly more activated than untreated PLTs, but irrespective of this increase in steady-state activation, CD62P and CD63 were strongly upregulated on both acid-treated and untreated PLTs after stimulation with thrombin receptor agonist peptide. Acid treatment did not induce apoptosis over time. X-ray irradiation did not significantly influence the expression of HLA Class I complexes, CD62P, CD63, and TEG variables on acid treated PLTs. CONCLUSION: The relatively simple acid stripping method can be used with irradiated apheresis PLTs and may prevent transfusion-associated HLA sensitization and overcome PLT refractoriness. CI - (c) 2021 The Authors. Transfusion published by Wiley Periodicals LLC. on behalf of AABB. FAU - Mirlashari, Mohammad Reza AU - Mirlashari MR AUID- ORCID: 0000-0003-0562-0025 AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. FAU - Vetlesen, Annette AU - Vetlesen A AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. FAU - Nissen-Meyer, Lise Sofie H AU - Nissen-Meyer LSH AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. FAU - Naper, Christian AU - Naper C AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. FAU - Tjonnfjord, Geir Erland AU - Tjonnfjord GE AD - Department of Hematology, Oslo University Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Njerve, Ida Unhammer AU - Njerve IU AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. FAU - Ezligini, Farshid AU - Ezligini F AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. FAU - Landmark, Brynjar Fowels AU - Landmark BF AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. FAU - Meinke, Stephan AU - Meinke S AD - Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden. AD - Function Area Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Sandgren, Per AU - Sandgren P AD - Function Area Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Hoglund, Petter AU - Hoglund P AUID- ORCID: 0000-0002-9233-626X AD - Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden. AD - Function Area Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Hetland, Geir AU - Hetland G AD - Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. LA - eng GR - Funding for this study was from University of Oslo and Oslo University Hospital./ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210213 PL - United States TA - Transfusion JT - Transfusion JID - 0417360 RN - 0 (Antibodies) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (P-Selectin) RN - 0 (Tetraspanin 30) RN - 2968PHW8QP (Citric Acid) RN - Bare Lymphocyte Syndrome, Type I SB - IM MH - Antibodies/immunology MH - Blood Grouping and Crossmatching/methods MH - Blood Platelets/radiation effects MH - Citric Acid/*adverse effects MH - Female MH - Histocompatibility Antigens Class I/*drug effects/immunology/metabolism/radiation effects MH - Histocompatibility Testing/economics/methods MH - Humans MH - P-Selectin/metabolism MH - Platelet Transfusion/adverse effects/*methods MH - Plateletpheresis/methods MH - Severe Combined Immunodeficiency/*chemically induced MH - Tetraspanin 30/metabolism MH - Thrombelastography/methods MH - Thrombocytopenia/therapy MH - Up-Regulation/genetics OTO - NOTNLM OT - hematology - platelets OT - immune thrombocytopenia OT - platelet transfusion EDAT- 2021/02/14 06:00 MHDA- 2021/07/20 06:00 CRDT- 2021/02/13 17:06 PHST- 2020/12/07 00:00 [revised] PHST- 2020/06/23 00:00 [received] PHST- 2020/12/17 00:00 [accepted] PHST- 2021/02/14 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] PHST- 2021/02/13 17:06 [entrez] AID - 10.1111/trf.16282 [doi] PST - ppublish SO - Transfusion. 2021 Apr;61(4):1222-1234. doi: 10.1111/trf.16282. Epub 2021 Feb 13.