Humanized monoclonal antibodies to Human Neutrophil Antigens

Dr. Kikuyo Taniguchi, a pioneering researcher in granulocyte immunobiology in Japan, successfully developed mouse monoclonal antibodies targeting HNA-1a, HNA-1b, HNA-2, and FcγRIIIb (the molecule carrying HNA-1a and HNA-1b) in the late 1990s (1,2). These monoclonals were named TAG-1 (anti-HNA-1a), TAG-2 (anti-HNA-1b), TAG-3 (anti-FcγRIIIb), and TAG-4 (anti-HNA-2). Dr. Taniguchi was also an active participant in the Granulocyte Workshop of the Japan Society of Blood Transfusion and Cell Therapy and contributed significantly to the ISBT Granulocyte Immunobiology Working Party, particularly in her role as a trainer and lecturer for training courses in Asian countries. More recently, using recombinant technology, we developed humanized versions of the TAG antibodies, which were named TAGH-1 to TAGH-4. These humanized monoclonals were confirmed to specifically react with HNA-1a (TAGH-1), HNA-2 (TAGH-4), and FcγRIIIa (TAG-3). However, TAGH-2 exhibited non-specific reactivity with HNA-1a, but this reactivity was limited to flow cytometry (granulocyte immunofluorescence test, GIFT) and was not observed in the MAIGA assay.

Despite the expectation that leukocyte reduction by filtration effectively prevents HLA and HNA immunization as well as negative transfusion effects in recipients, filtration is known to induce the release of neutrophil granules in the supernatant4,5. Accordingly, our analysis suggests that despite the effective elimination of leukocytes from the erythrocytes by filtration, the trapped leukocytes on the filter tend to be activated and therefore release soluble CD177/PR3. In addition, a significantly increased CD177/PR3 concentration was documented in the stored red cells after filtration compared to fresh red cell concentrate; this indicates an additional effect of storage on the release of CD177/PR3 from leukocytes and thus an increased concentration of this antigen in the filtered red cell concentrate6.