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Letters to the Editor
remaining 209 patients, eleven (5.3%) patients who did not have alloantibodies against the standard three-cell screen panel, had a total of eleven antibodies against African antigens; three anti-Dantu (for one, confirmation by a second Dantu+ test cell was not performed, due to lack of Dantu+ cells), two anti-He, two anti-V/VS, one anti-VS, one anti-RH32, one anti-Goa and one antibody probably against a low frequency antigen but no plasma was available for further investigation (Table 1).
Overall, 31.4% of alloimmunized patients had antibod- ies against African antigens that were not detected during standard antibody screening. Other studies in patients with SCD have reported antibodies against African anti- gens5-13 but these patients were transfused in the US and Europe and thus not exclusively with blood from African donors. Furthermore, these antibodies were encountered during complex antibody workup, crossmatch incompat- ibilities and hemolytic transfusion reactions rather than through systematic screening. The antibody frequency against African antigens in these studies ranged from 0.7% to 13.3%, with anti-V/VS, anti-Jsa and anti-Goa rep- resenting 90% of specificities. So far, only one study in France systematically screened a heavily transfused patient cohort with SCD using selected African red cells. After receiving a mean of 144 RBC transfusions (11.5% from donors of African descent) 5.2% of 211 patients had antibodies against African-specific antigens (MNS6, RH10, RH20, RH23, RH30 and KEL6).14 However, unlike our study, these patients received blood matched for major Rh and K antigens, which precludes insight in dif- ferences in immunogenicity of African and the classical ‘major’ blood group antigens. Surprisingly, in our study seven of 36 (19%) antibodies were against low frequency African antigens (i.e., Goa 2%, RH32 1%, He 1% and Dantu 0.5% in Africans).1 This suggests that these anti- gens are immunogenic in Ghanaians and may be more immunogenic than antigens for which we test in the European setting. The results from these studies stress the importance of testing against African antigens when patients receive transfusions from African donors.
Antibodies in patients with SCD are notorious for their high evanescence rate, which may be up to 60-80%.15 Because our study had a cross-sectional design, it is likely that antibody frequency was underestimated. In the French study, none of the eight previously detected African antibodies, were detectable at study enrollment, suggesting that African antibodies also have a high evanescence rate.14 Furthermore, African antibodies have been implicated in severe hemolytic transfusion reactions upon receipt of transfusions with the cognate antigens.12
Our study was limited by the scarcity of test cells expressing African antigens, so antibodies against other African antigens, such as RH49 (STEM), GE6 (Lsa) and CROM3 (Tcb), might have been missed.1 Furthermore, antibodies against antigens that are more frequently expressed on RBC of Ghanaian donors might have been missed, because we did not specifically test Ghanaian RBC.
Since we found African antibodies in African patients transfused with African blood, it is also quite likely that similar antibodies may be elicited in Caucasian patients receiving blood from African donors and through preg- nancy. These antibodies cannot be detected during pre- transfusion antibody screening using standard test cells and without performing an indirect antiglobulin cross- match with donor cells (and many countries only per- form type and screen). Our findings are relevant for blood banks in Western countries since many are devel- oping strategies to recruit more African donors. Unless
they can supply antigen compatible blood, African anti- bodies may increasingly be missed as the pool of African donors expands.
This is the first study to systematically screen for RBC antibodies against African antigens in a large cohort of transfused patients with SCD who were exclusively transfused with blood from African donors. In order to increase the availability of test cells with African anti- gens, African donors should be typed, for relevant anti- gens and then retain them as repeat donors for the prepa- ration of test cells. As long as antigens commonly expressed in Africans are not incorporated on the RBC testing panel, transfusions for patients with SCD should be cross-matched using an indirect antiglobulin test, even when they do not have RBC antibodies using the stan- dard three-cell screen panel.
Lilian A. Boateng,1,2 Henk Schonewille,3 Peter C. Ligthart,3 Ahmad Javadi,3 Barbera Veldhuisen,3 Alex Osei-Akoto,4,5 Yvonne Dei-Adomakoh,6,7 Imelda Bates1 and C. Ellen van der Schoot3
1Center for Capacity Research, International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK; 2Medical Diagnostics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; 3Experimental Immunohaematology, Sanquin, Amsterdam, the Netherlands; 4Child Health, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; 5Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, Ghana; 6Hematology, University of Ghana Medical School, University of Ghana, Accra, Ghana and 7Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital, Adult Sickle Cell Clinic, Accra, Ghana
Correspondence:
LILIAN A. BOATENG - lilian.boateng@lstmed.ac.uk doi:10.3324/haematol.2021.278451
Received: January 28, 2021.
Accepted: March 11, 2021.
Pre-published: April 1, 2021.
Disclosures: the authors declare no competing financial interests.
Contributions: LB, HS, AO, YD, EVS and IB conceived the idea and designed the study; LB, PL, AJ and BV performed the laboratory test and interpreted the results; LB, HS, IB and EVS analyzed and interpreted the data; LB and HS drafted the manuscript.
Acknowledgments: the authors would like to thank the staff, patients and donors at the sickle cell clinics and blood banks in KATH and KBTH, Ghana, for their contributions in obtaining blood samples for the research project.
Funding: this work was supported by grant GHCA-2017-18 to LB, from the Commonwealth Scholarship Commission, UK and from Sanquin Blood Supply, The Netherlands.
References
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2. Haer-Wigman L, Veldhuisen B, Jonkers R, et al. RHD and RHCE vari- ant and zygosity genotyping via multiplex ligation–dependent probe amplification. Transfusion. 2013;53(7):1559-1574.
3. von Zabern I, Wagner FF, Moulds JM, Moulds JJ, Flegel WA. D cate- gory IV: a group of clinically relevant and phylogenetically diverse partial D. Transfusion. 2013;53(11pt2):2960-2973.
4. Wagner FF, Frohmajer A, Ladewig B, et al. Weak D alleles express dis- tinct phenotypes. Blood. 2000;95(8):2699-2708.
5. Rosse WF, Gallagher D, Kinney TR, et al. Transfusion and alloimmu- nization in sickle cell disease. Blood. 1990;76(7):1431-1437.
6. Telen MJ, Afenyi-Annan A, Garrett ME, Combs MR, Orringer EP, Ashley-Koch AE. Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival. Transfusion. 2015;55(6 Pt 2):1378-1387.
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