Secondary anti-D immunization by Del red blood cells

Background: Recent molecular studies of the RHD gene have revealed that D-el individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. No D-el phenotype has yet been shown to induce a primary or secondary alloanti-D immunization, however. Case Report: A 67-year-old D- Japanese woman with a history of allosensitization from transfusion of D+ red blood cells (RBCs) was negative for anti-D at admission. After she received RBCs from 19 apparently D-donors, she developed anti-D with an 8-fold titer. The titer of anti-D increased further to 128-fold after transfusions of cross-match-compatible D-negative RBCs from 40 donors over the next 2 years. Two of 59 donors were found to be RHD gene-positive and antigen D- with a D-el phenotype, that is, RHD(K409K). Conclusion: This is the first case in which RBCs having the D-el phenotype induced a secondary alloanti-D immunization. A D- donor with the RHD(K409K) allele was associated with the development of anti-D. Adverse episodes or evidence of hemolysis was not observed after the transfusion of RHD(K409K) RBCs. Further clinical evidence is needed to reveal whether the D-el phenotype has a clinically relevant potential for anti-D immunization.