Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: Evers, Dorothea; Middelburg, Rutger A; de Haas, Masja; Zalpuri, Saurabh; de Vooght, Karen M K; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C; Hudig, Francisca; Schonewille, Henk; Zwaginga, Jaap Jan; van der Bom, Johanna G
• Is Part Of: Lancet. Volume 3:Issue 6(2016)
• Page Start: e284
• Page End: e292
• Publication Date: 2016-06
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15005
• DOI: 10.1016/S2352-3026(16)30019-9
• Languages: English
• ISSNs: 2352-3026

Abstract

Summary: 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.