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.


RESULTS
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).


CONCLUSIONS
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.


BACKGROUND
None.
Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands.
Dorothea
D
Evers
Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands; Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, Netherlands.
Rutger A
RA
Middelburg
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.
Masja
M
de Haas
Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands.
Saurabh
S
Zalpuri
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, Netherlands.
Karen M K
KM
de Vooght
Department of Clinical Chemistry and Haematology, Catharina Hospital, Eindhoven, Netherlands.
Daan
D
van de Kerkhof
Department of Haematology, VU Medical Center, Amsterdam, Netherlands.
Otto
O
Visser
Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands.
Nathalie C
NC
Péquériaux
LabWest, Haga Teaching Hospital, The Hague, Netherlands.
Francisca
F
Hudig
Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands.
Henk
H
Schonewille
Center for Clinical Transfusion Research, Sanquin Research, Leiden, Netherlands; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands.
Jaap Jan
JJ
Zwaginga
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.
Johanna G
JG
van der Bom
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001789:Blood Group Antigens / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000097:blood / Q000453:epidemiology* / Q000276:immunology; D001788:Blood Grouping and Crossmatching / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D017707:Erythrocyte Transfusion; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D015996:Survival Rate; D065227:Transfusion Reaction / Q000276:immunology*; D055815:Young Adult
D001789:Blood Group Antigens; D007518:Isoantibodies