HLA class I depletion by citric acid, and irradiation of apheresis platelets for transfusion of refractory patients
| Autor: | Lise Sofie H. Nissen-Meyer, Farshid Ezligini, Annette Vetlesen, Petter Höglund, Per Sandgren, Mohammad Reza Mirlashari, Stephan Meinke, Brynjar Landmark, Christian Naper, Ida Unhammer Njerve, Geir E. Tjønnfjord, Geir Hetland |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Blood Platelets
Immunology Complement factor I Human leukocyte antigen Platelet Transfusion 030204 cardiovascular system & hematology Antibodies Citric Acid Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Immunology and Allergy Humans Platelet medicine.diagnostic_test biology CD63 Chemistry Tetraspanin 30 Histocompatibility Testing Histocompatibility Antigens Class I Plateletpheresis Hematology Phosphatidylserine Thrombocytopenia Thrombelastography Up-Regulation P-Selectin Apheresis Blood Grouping and Crossmatching biology.protein Female Severe Combined Immunodeficiency Antibody 030215 immunology |
| ISSN: | 0041-1132 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text