IVS5‐38del4 deletion in the RHD gene does not cause a DEL phenotype: relevance for RHD alleles including DFR‐3

We read with interest the report by Lee and colleagues regarding the molecular basis of KEL29 (KALT) and KEL30 (KTIM), two novel high-prevalence antigens in the Kell blood group system. KEL29 antigen was identified in a Mexican woman with a homozygous 1988G>A polymorphism in exon 17, which is predicted to encode lysine instead of arginine at amino acid position 623. Interestingly, her serum sample contained an alloantibody identified as anti-KEL29 (anti-KALT) that did not agglutinate trypsin-treated RBCs. KEL30 antigen was identified in an American woman with history of transfusion and pregnancies with a homozygous 1033G>A polymorphism in exon 8, which is predicted to encode asparagine instead of aspartic acid at amino acid position 305. Her serum sample contained anti-KEL30 (anti-KTIM), which agglutinated against papain, trypsin, or a-chymotrypsin–treated RBCs. Because there are no data about the frequency of the KEL*29 and KEL*30 alleles in different populations, we performed a study to determine the frequency of the wildtype and variant KEL*29 and KEL*30 alleles in Brazilian persons. Employing the PCR-TfiI-RFLP and PCR-TaqIRFLP techniques described by Lee and coworkers, we studied 300 random blood donors representing a Brazilian population with a high rate of racial admixture and 68 Brazilian patients of African descent with hemoglobinopathies (45 HbSS, 4 HbS-thal, 15 HbSC, and 4 HbCC). All 300 donors (100%) and 68 patients (100%) were homozygous for wild-type consensus nucleotides at the KEL*29 and KEL*30 positions. No variant 1988G>A KEL*29 or 1033G>A KEL*30 alleles were identified among the 736 alleles that were analyzed. The Kell system is distinguished by its complexity and at present includes 27 known antigens, which may be classified into five antithetical sets of highand low-incidence antigens: KEL1 (K) and KEL2 (k); KEL3 (Kp), KEL4 (Kp), and KEL21 (Kp); KEL6 (Js) and KEL7 (Js); KEL11 and KEL17; and KEL14 and KEL24. In addition, there are 16 independently expressed antigens, 4 low-incidence (KEL10 [Ul], KEL23, KEL25 [VLAN], KEL28 [VONG]), and 12 high-incidence (KEL5 [Ku], KEL12, KEL13, KEL16, KEL18, KEL19, KEL20 [Km], KEL22, KEL26 [TOU], KEL27 [RAZ], KEL29 [KALT], KEL30 [KTIM]). The low-incidence antigens reflect single-nucleotide polymorphisms in the KEL exons and some of them show ethnic or racial specificity. Kell antigens are important in transfusion medicine owing to their strong immunogenicity. Alloantibodies to Kell antigens can cause either hemolytic transfusion reactions or hemolytic disease of the newborn. Most of these alloantibodies are directed against KEL1 and other low-incidence Kell antigens. Alloantibodies to high-incidence Kell antigens have been reported, however. Our data suggest that the KEL29 and KEL30 antigens have little clinical impact, because the alloimmunization by these antigens is probably a very rare event, restricted to a few cases involving subjects with KEL: -29 or KEL: -30 phenotype. Edmir Boturão-Neto, MD José O. Bordin, MD, PhD Discipline of Hematology and Hemotherapy Federal University of Sao Paulo Escola Paulista de Medicina São Paulo, SP, Brazil e-mail: jobordin@hemato.epm.br