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The Knops blood group system (ISBT 022) is located on the complement receptor 1 (CR1) which is encoded on chromosome 1q32.2. It consists of 13 antigens: Kna/b, McCa/b, SI1/Vil, KCAM/KDAS, Sl3 (encoded in exon 29), Yka (exon 26), DACY and YCAD (exon 22), and KNMB (exon 21).1 Antibodies to the Knops antigens are not clinically significant but are common and often difficult to identify because the antigen profile is not indicated on commercial antibody identification panels. Reactions with different panel test cells usually vary in strength and can mimic other specificities. Using recombinant Kna/DACY and YCAD blood group antigens, most Knops antibodies can be inhibited. However, they are often a challenge in pre-transfusion diagnostics. We describe a patient whose plasma contained anti-E and an antibody to a new high-prevalence Knops antigen. The antibody identification was performed in the gel technique using untreated and papain treated antibody identification panels (BioRad, Cressier, Switzerland) and an in-house identification panel. The in-house panel consisted of donor red cells, phenotyped for the common antigens and genotyped for 66 blood group alleles as previously described.2 Recombinant Kna/DACY blood group antigens (inno-train Diagnostik GmbH, Kronberg, Germany) were used according to the manufacturer's procedure. Sanger sequencing of exon 26–29 of patient's CR1 was performed. A total of 104 blood donors of blood group O, RhE negative, were serologically screened with the patient's serum in the gel technique (DG Gel Coombs, Grifols, Barcelona, Spain). Donors whose red cells were compatible were genotyped in an SSP-PCR for c.4619A>G (rs17259045, chr1:207609362, GRCh38.p14).3 For this typing variant, sequence-specific primers were designed (single nucleotide variant [SNV] specific KN-4619G-F3: 5′-GCAACAATAGAACATCTTTTCGCAG-3′; wild type KN-4619A-F3: 5′-GCAACAATAGAACATCTTTTCGCAA-3′; CR1 specific KN-i29-r1: 5′-TATACGTACCCTCACACCCAG-3′) and performed according to our in-house protocol.4 A 67-year-old Caucasian male patient with transfusion history presented a panreactive red cell antibody. The reactions varied in strength and were slightly enhanced with papain treated test cells. The antibody was inhibited with the recombinant Kna/DACY protein showing an additional anti-E. Screening 104 blood donors with the patient's plasma revealed one single donor whose red cells were negative. In our in-house panel 2 of 10 test cells were also negative (Figure 1). Sanger sequencing of exon 26–29 of the patient's CR1 showed homozygosity for the c.4619A>G mutation in exon 29 resulting in Asn1540Ser, which was described before in association with Alzheimer's disease but was not associated with a blood group antigen.5 The patient's genotype was: KN*01.-05 (Yk(a)-). Genotyping of the three unrelated donors whose red cells were negative with the patient's plasma revealed homozygosity for the c.4619A>G in all three individuals. Additional genotyping of 470 blood donors in our population showed 101 donors positive for c.4619G, resulting in a prevalence of 21.5%, indicating 20.2% (95) heterozygous and 1.3% (6) homozygous donors. We describe a new high prevalence antigen of the Knops blood group system named KNEH. The antigen number KN14 was assigned by the ISBT working party on Red Cell Immunogenetics and Blood Group Terminology at the ISBT meeting (Milan, Italy, June 2025). The name was derived from KN for Knops and the surname of the patient. The molecular background is defined by the SNV c.4619A>G of the reference allele. KNEH− is defined as c.4619G (rs17259045) in CR1, resulting in an amino change in the Knops protein from Asn (KNEH+) to Ser (KNEH−) at position 1540 (p. Asn1540Ser). The allele frequency reported in the dbSNP database for SNV rs17259045 is 9.4% (ALFA) for c.4619G (KNEH−) and 90.6% for the reference allele across most populations.3 Assuming Hardy–Weinberg allele distribution, 0.9% KNEH− homozygous individuals are expected, with lower numbers for Africans (0.06%). Open access funding provided by Paracelsus Medizinische Privatuniversitat/KEMÖ. The study received no financial support through grants, equipment, or drugs. The authors have disclosed no conflicts of interest.