Gabriele Rink (Mannheim/ DE), Anette Stürtzel (Baden-Baden/ DE), Prof. Dr. Erwin Andreas Scharberg (Baden-Baden/ DE), Dr. Elke Weinig (Freiburg i. Br./ DE), Dr. Christof Weinstock (Ulm/ DE), Prof. Dr. Harald Klüter (Mannheim/ DE), Prof. Dr. Peter Bugert (Mannheim/ DE)
Background
The antigens of the Knops blood group system (KN; ISBT 022) are located on the complement receptor 1 (CR1), a large glycoprotein composed of 4 Long-Homologous-Repeats (LHR-A, -B, -C, -D). Most KN antigens are located LHR-D, except for KN11/KN12 and KNMB located in LHR-C. Antibodies to KN antigens are not clinically relevant but they are common in patients. Here, we sequenced the CR1 gene in patients with suspected alloantibodies to KN antigens.
Methods
Serologic work-up identified 23 cases with suspected antibodies against a high prevalence antigen in the Knops blood group system. The ethnic background of the patients was European (15 cases) or African (8 cases). All cases were subjected to Massively Parallel Sequencing (MPS) of all 39 exons of the CR1 gene included in the targeted panel of all blood group genes. Allele frequencies of the identifed gene variants in different populations were taken from the gnomAD database.
Results
The CR1 sequence in 2 of the European cases showed homozygosity for the KN*01.–05 allele (c.4223C>T; p.T1408M) indicating absence of the Yk(a) antigen. Homozygosity for the KN*01.–08 allele (c.4828T>A; p.S1610T) indicating absence of the Sl3 antigen was identified in 2 European cases. In 8 cases we found heterozygosity for at least one known KN allele or rare CR1 variant. The other 3 European cases showed no CR1 variation. Two of the African cases were homozygous for CR1 c.3290T>C (p.L1097P) and further serologic investigation showed that the variant defines a new high prevalence antigen named KNMB. Each of the other 6 African cases revealed heterozygosity for at least 2 known KN alleles or rare CR1 variants.
Conclusion
MPS simplified the molecular analysis especially of blood group systems with large genes such as CR1 for the KN system. The systematic case work enabled the identification of the new KN antigen KNMB. The significantly different frequency in African and European populations of CR1 variants encoding KN antigens may result in an increased risk of alloimmunization evoked by blood transfusion.
Offenlegung Interessenkonflikt:
No conflicts of interest
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