Characterization of CD177-reactive iso- and auto-antibodies.

Annalena Traum, Christine Hofmann, Sabine Haas, Silke Schmidt, Gregor Bein, Ulrich J Sachs, Behnaz Bayat

Transfusion 2021 Jun

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CD177 is a surface protein on neutrophils and a main mediator for the surface expression of proteinase 3 (PR3). Its functions are largely unknown. At least three types of antibodies have been described to target CD177: isoantibodies, which are formed in CD177-null individuals as a result of an immune reaction following transfusion or pregnancy; autoantibodies present in sera from patients with autoimmune neutropenia; and antineutrophil cytoplasmic antibodies in sera from patients with glomerulonephritis with polyangiitis. In this study, we aimed to compare the binding characteristics of auto- and iso-antibodies to optimize their detectability in the neutrophil serology laboratory. The reactivity of iso- and auto-antibodies against CD177 was studied using granulocytes, "native" CD177/PR3 complex, and recombinant CD177 or PR3. All iso- and auto-antibodies were reactive with CD177/PR3 when immobilized with monoclonal antibody (moab) 7D8. Seventy-five percent of autoantibodies, but none of the isoantibodies, did not react with CD177/PR3 immobilized with moab MEM166. The majority of autoantibodies did not react with recombinant CD177, whereas most isoantibodies tested positive. Our results suggest that iso- and auto-antibodies against CD177 target different epitopes. Isoantibodies mainly target CD177 alone, while the majority of autoantibodies target a native epitope present on the neutrophil surface, but absent from recombinant CD177 which lacks PR3. Moab MEM166 binds to the native epitope and hinders the binding of CD177 autoantibodies. The results may help to design diagnostic strategies, especially for the identification of autoantibodies. © 2021 The Authors. Transfusion published by Wiley Periodicals LLC. on behalf of AABB.

Citation

Annalena Traum, Christine Hofmann, Sabine Haas, Silke Schmidt, Gregor Bein, Ulrich J Sachs, Behnaz Bayat. Characterization of CD177-reactive iso- and auto-antibodies. Transfusion. 2021 Jun;61(6):1916-1922