EXPRESS: Experimental Evaluation of the Immunogenicity of Feline Erythrocyte Antigen 6 (FEA 6) in Transfusion-Naive FEA 6-Negative Cats

Objectives Feline Erythrocyte Antigen 6 (FEA 6) is a newly identified red blood cell (RBC) antigen in cats discovered following an unintentional sensitization event, suggesting it can be immunogenic. Its ability to consistently induce alloimmunization remains unknown. This prospective study evaluated FEA 6 immunogenicity in transfusion-naive, FEA 6-negative cats by assessing anti-FEA 6 alloantibody production and plasma levels. A secondary objective was to bank polyclonal anti-FEA 6 antibodies. Methods Fifty-three cats underwent AB and extensive blood typing for FEAs 1–6, naturally occurring alloantibody (NOAb) screening, and compatibility testing to select donor-recipient pairs. FEA 6 prevalence was assessed in 82 type A cats. Two transfusion-naive, FEA 6-negative cats received FEA 6-positive, otherwise compatible RBC transfusions and were monitored for anti-FEA 6 alloantibody production by gel column agglutination. Repeat transfusions were performed if alloantibodies became undetectable. Agreement between recipient-derived and reference anti-FEA 6 alloantibodies was evaluated in 51 type A cats using kappa statistics. Results FEA 6 prevalence among type A cats was 75.6% (62/82); NOAb were detected in 10.3% of screened type A cats, but none were directed against FEA 6. Both recipients developed anti-FEA 6 alloantibodies. Recipient 1 responded after two sensitizations, whereas recipient 2 responded after a single transfusion. Both reached peak titers of 1:8, with alloantibodies detectable through days 372 and 200, respectively. Recipient-derived anti-FEA 6 alloantibodies showed substantial agreement with the reference anti-FEA 6 antibody (κ = 0.64–0.78, P < .001) and almost perfect agreement with each other (κ = 0.87, P < .001). Conclusions and relevance Transfusion of FEA 6-positive RBCs induced anti-FEA 6 alloantibodies in all transfusion-naive, FEA 6-negative recipients, supporting FEA 6 immunogenicity and its likely contribution to unexplained post-transfusion alloantibodies in cats. The resulting polyclonal antibodies may support FEA 6 typing and transfusion research, although more durable reagents remain needed.