(P-IG-31) JK*01 Allele with c.299C >T (p.Thr100Ile) Associated with Lack of Jk^a Expression

Background/Case Studies: The JK blood group system includes antithetical antigens Jk^a and Jk^b, encoded by alleles of the SLC14A1 gene that include c.838G or A, respectively. There are 10 JK*01 alleles that encode Jka+^w and 21 JK*01 null alleles as well as six JK*02 alleles that encode Jkb+^w and 20 null JK*02 alleles. Here we present a novel JK*01 null allele found in two African American blood donors.

Study

Design/Methods: The blood donors’ RBCs were typed using standard agglutination methods. Adsorption/elution studies were performed using a polyclonal source of anti-Jk^a. Molecular testing was performed using HemoID DQS (Agena Biosciences). Sanger sequencing of the coding exons of SLC14A1 was performed, and results were aligned to the reference sequence using Sequencher software (GeneCodes).

Results/Findings: Both donor RBCs typed Jk(a-b+). HemoID DQS testing predicted the donor to type Jk(a+b+). Sequencing of SLC14A1 confirmed that both donors were heterozygous for c.838G/A (Asp280Asn) and heterozygous for the common synonymous single nucleotide variant (SNV) c.588A >G. Additionally, both donors were heterozygous for c.299C/T (p.Thr100Ile). The c.299C >T SNV (rs1381249141) is extremely rare with a frequency in GnomAD of 0.0000029. Although the testing is unable to determine the phase of the variant in relation to the c.838G/A variant responsible for Jk^a/Jk^b, based on the serology, it is likely that the c.299T SNV is on the JK*01 allele with c.838G. This variant is not listed on the ISBT 009 JK blood group allele table (v8.3) posted on isbtweb.org/isbt-working-parties/rcibgt.html. The eluate from the adsorption/elution studies did not contain anti-Jk^a.

Conclusions: Investigation of antigen typing discrepancies involving discordant serologic and molecular test results is important to the resolution of the donor antigen type and, additionally, can identify novel alleles. In the case of this novel JK*01 allele found in two blood donors, serological testing for Jk^a, as well as performance of the more sensitive adsorption/elution technique, did not detect the expression of Jk^a on the surface of the donor RBCs, supporting this as the 27^th JK*01 null allele.