Immunohematology and Genetic Testing (red cells, leukocytes and platelets)
Opal Reddy, MD
Department of Pathology, Keck Hospital of USC and USC Norris Cancer Hospital, Los Angeles, California, USA.
Los angeles, California, United States
Variant JK alleles encoding changes associated with altered antigen expression producing weak or partial JK antigens were characterized mostly in donors. Only rare cases have been reported in patients. Anti-JK auto- or allo-antibodies associated with hemolysis have been reported. The clinical significance of anti-JK in patients with variant JK alleles is unclear and systematic review is needed to inform clinical management.
Study
Design/Methods:
A retrospective review is performed to examine prevalence of variant JK alleles and the clinical significance of anti-JK among patients who developed potential auto- vs allo- anti-Kidd antibodies at two urban academic medical centers.
Results/Findings:
Between 2018-2023 (center 1) and 2020-2023 (center 2), 12 patients with suspected allo- vs auto-anti-JK antibodies were identified (9 anti-Jka , 3 anti-Jkb). Nine (75%) were sent for molecular variant analysis. Variant alleles were detected in 7 of 9 patients (78%). All cases were heterozygous for variant allele JK*01W.01, exon 3 c.130G/A (p.44Glu/Lys). All were heterozygous for exon 8 c.838G(p.280Asp) and c.838A(p.280Asn) encoding for JK*A and JK*B, respectively, except for one homozygous for JK*A. The variant alleles are presumed to be applicable to JK*A in all cases except for one case where JK*B is also a possibility. Variant alleles were detected in all three patients of Asian race/ethnicity and 4 of 6 patients of Hispanic/Latin race/ethnicity. Majority of anti-JK antibodies (at least 5 of 7) were best detected or only detected by the solid phase red cell adherence assay and majority showed evanescence. Chart review of 5 cases with variant alleles and no conventional copies showed no definitive cases of clinically significant hemolysis. At least four of seven cases with variant alleles had evidence of concurrent, historical, or subsequent warm autoantibodies of broad specificity identified, as compared with 2 of 2 cases without variant alleles.
Conclusions:
Among Hispanic and Asian patients with suspected auto- vs allo- anti-JK antibodies, variant allele (JK*01W.01) occur frequently, is often associated with warm autoantibodies of broad specificity, and no definitive cases of clinically significant hemolysis in this series. Given rarity of clinically significant hemolysis and high rates of variants in Asian and Hispanic patients, a conservative practice in providing antigen negative RBCs, if time and supply allow, may be a reasonable alternative to clinically triaged variant testing approaches in these patient populations.
Importance of research: Variant JK alleles have been characterized extensively in donors but only rarely described in patients, usually as case reports. It is unclear whether anti-JK in patients harboring variant JK alleles is clinically significant. A systematic study is needed to inform clinical management. To our knowledge, this is the first larger study examining clinical significance of anti-JK in patients with variant JK alleles.