Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: A cohort study

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.