Dorothea Evers1, Rutger A Middelburg2, Masja de Haas3, Saurabh Zalpuri4, Karen M K de Vooght5, Daan van de Kerkhof6, Otto Visser7, Nathalie C Péquériaux8, Francisca Hudig9, Henk Schonewille4, Jaap Jan Zwaginga1, Johanna G van der Bom10. 1. Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands. 2. Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands; Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, Netherlands. 3. Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands; Department of Immunohaematology Diagnostics, Sanquin, Amsterdam, Netherlands. 4. Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands. 5. Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, Netherlands. 6. Department of Clinical Chemistry and Haematology, Catharina Hospital, Eindhoven, Netherlands. 7. Department of Haematology, VU Medical Center, Amsterdam, Netherlands. 8. Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands. 9. LabWest, Haga Teaching Hospital, The Hague, Netherlands. 10. Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands; Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, Netherlands. Electronic address: j.g.vanderbom@lumc.nl.
Abstract
BACKGROUND: Matching donor red blood cells based on recipient antigens prevents alloimmunisation. Knowledge about the immunogenicity of red-blood-cell antigens can help optimise risk-adapted matching strategies. We set out to assess the immunogenicity of red-blood-cell antigens. METHODS: In an incident new-user cohort of previously non-transfused, non-alloimmunised white patients receiving non-extended matched red-blood-cell transfusions in six Dutch hospitals between 2006 and 2013, we determined the cumulative number of mismatched red-blood-cell units per patient. We used multiple imputation to address missing antigen data. Using Kaplan-Meier analysis, we estimated cumulative alloimmunisation incidences per mismatched antigen dose as a measure of immunogenicity. FINDINGS:Of 54 347 patients assessed, 21 512 were included in our study. Alloantibodies occurred in 474 (2·2%) of all transfused patients, with cumulative alloimmunisation incidences increasing up to 7·7% (95% CI 4·9-11·2) after 40 units received. The antigens C, c, E, K, and Jk(a) were responsible for 78% of all alloimmunisations in our cohort. K, E, and C(w) were the most immunogenic antigens (cumulative immunisation incidences after 2 mismatched units of 2·3% [95% CI 1·0-4·8] for K, 1·5% [0·6-3·0] for E, and 1·2% [0·0-10·8] for C(w)). These antigens were 8·7 times (for K), 5·4 times (for E), and 4·6 times (for C(w)) as immunogenic as Fy(a). The next most immunogenic antigens were, in order, e (1·9 times as immunogenic as Fy(a)), Jk(a) (1·9 times), and c (1·6 times). INTERPRETATION: Red-blood-cell antigens vary in their potency to evoke a humoral immune response. Our findings highlight that donor-recipient red-blood-cell matching strategies will be most efficient when primarily focusing on prevention of C, c, E, K, and Jk(a) alloimmunisation. Matching for Fy(a) is of lower clinical relevance. Variations of antigen frequencies determined by ethnic background prevent extrapolating these conclusions to non-white populations. FUNDING: None.
RCT Entities:
BACKGROUND: Matching donor red blood cells based on recipient antigens prevents alloimmunisation. Knowledge about the immunogenicity of red-blood-cell antigens can help optimise risk-adapted matching strategies. We set out to assess the immunogenicity of red-blood-cell antigens. METHODS: In an incident new-user cohort of previously non-transfused, non-alloimmunised white patients receiving non-extended matched red-blood-cell transfusions in six Dutch hospitals between 2006 and 2013, we determined the cumulative number of mismatched red-blood-cell units per patient. We used multiple imputation to address missing antigen data. Using Kaplan-Meier analysis, we estimated cumulative alloimmunisation incidences per mismatched antigen dose as a measure of immunogenicity. FINDINGS: Of 54 347 patients assessed, 21 512 were included in our study. Alloantibodies occurred in 474 (2·2%) of all transfused patients, with cumulative alloimmunisation incidences increasing up to 7·7% (95% CI 4·9-11·2) after 40 units received. The antigens C, c, E, K, and Jk(a) were responsible for 78% of all alloimmunisations in our cohort. K, E, and C(w) were the most immunogenic antigens (cumulative immunisation incidences after 2 mismatched units of 2·3% [95% CI 1·0-4·8] for K, 1·5% [0·6-3·0] for E, and 1·2% [0·0-10·8] for C(w)). These antigens were 8·7 times (for K), 5·4 times (for E), and 4·6 times (for C(w)) as immunogenic as Fy(a). The next most immunogenic antigens were, in order, e (1·9 times as immunogenic as Fy(a)), Jk(a) (1·9 times), and c (1·6 times). INTERPRETATION: Red-blood-cell antigens vary in their potency to evoke a humoral immune response. Our findings highlight that donor-recipient red-blood-cell matching strategies will be most efficient when primarily focusing on prevention of C, c, E, K, and Jk(a) alloimmunisation. Matching for Fy(a) is of lower clinical relevance. Variations of antigen frequencies determined by ethnic background prevent extrapolating these conclusions to non-white populations. FUNDING: None.
Authors: Dorothea Evers; Jaap Jan Zwaginga; Janneke Tijmensen; Rutger A Middelburg; Masja de Haas; Karen M K de Vooght; Daan van de Kerkhof; Otto Visser; Nathalie C V Péquériaux; Francisca Hudig; Johanna G van der Bom Journal: Haematologica Date: 2016-09-15 Impact factor: 9.941
Authors: Dorothea Evers; Johanna G van der Bom; Janneke Tijmensen; Masja de Haas; Rutger A Middelburg; Karen M K de Vooght; Daan van de Kerkhof; Otto Visser; Nathalie C V Péquériaux; Francisca Hudig; Jaap Jan Zwaginga Journal: Haematologica Date: 2017-04-14 Impact factor: 9.941
Authors: Camila Caram-Deelder; Aukje L Kreuger; Dorothea Evers; Karen M K de Vooght; Daan van de Kerkhof; Otto Visser; Nathalie C V Péquériaux; Francisca Hudig; Jaap Jan Zwaginga; Johanna G van der Bom; Rutger A Middelburg Journal: JAMA Date: 2017-10-17 Impact factor: 56.272