Antibodies against human neutrophil antigens in non-transfused women with red blood cell alloimmunisation induced by pregnancy

Alloantibodies against human neutrophil antigens (HNA) resulting from allogeneic exposure may be associated with transfusion-related acute lung injury and immune neutropenia. Understanding the risk factors for the formation of such antibodies could have a great impact on the adoption of measures to prevent potentially fatal transfusion reactions. The aim of the study was to determine the prevalence of anti-HNA alloantibodies in non-transfused pregnant women with and without red blood cell (RBC) alloantibodies. HNA alloantibodies were investigated in blood samples from 147 pregnant women with RBC alloimmunisation induced by pregnancy as the only allogeneic stimulus (group 1). The control group (group 2) consisted of 563 women with at least one pregnancy without RBC alloimmunisation. Both groups were investigated for the presence and identity of HNA alloantibodies using granulocyte agglutination tests, white blood cell immunofluorescence testing, and the bead-based LABScreen Multi Kit. Genotyping was performed to confirm the specificity of the HNA alloantibodies. Group 1 women had a statistically higher number of HNA alloantibodies compared to group 2 women (9/147 [6.1%] vs 9/563 [1.6%]; p=0.005, OR=4.01; 95% CI 1.5-10.3). Considering only multiparous women, there was a higher statistical significance for the difference in the presence of HNA alloantibodies between the two groups (7/82 [8.5%] vs 9/493 [1.8%]; p=0.002, OR=5.02; 95% CI 1.8-13.9). Our data show that RBC alloimmunisation is significantly associated with the development of anti-HNA alloantibodies, corroborating the hypothesis that some individuals are better immune responders and react strongly to allogeneic exposure. The presence of RBC alloantibodies can, therefore, facilitate the identification of individuals with a higher risk of alloimmunisation to antigens from other cells, also acting as a tool to avoid potentially fatal transfusion reactions.