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Anti-HNA-2a antibodies implicated in TRALI and ANN demonstrate serological variability and different epitope preferences
Abstract   Peer reviewed

Anti-HNA-2a antibodies implicated in TRALI and ANN demonstrate serological variability and different epitope preferences

P J Hassell, R M Minchinton, D F Stroncek, R M Schuller and Yoke Lin Fung
Transfusion, Vol.49(Supplement 3), p.198A
American Association of Blood Banks (AABB) Annual Meeting and TXPO, 2009 (New Orleans, United States, 24-Oct-2009–27-Oct-2009)
2009
DOI: https://doi.org/10.1111/j.1537-2995.2009.02366.x
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https://doi.org/10.1111/j.1537-2995.2009.02366.xView
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Abstract

Clinical Sciences Cardiovascular Medicine and Haematology Immunology
Background Published case reports of transfusion-related acute lung injury (TRALI) indicate that antibodies (Abs) to HNA-3a have been associated with TRALI fatalities. In contrast there have been no reported fatalities in TRALI cases with Abs to HNA-1a and HNA-2a. Serological characteristics of each of these Abs may therefore be important in determining whether the reaction is mild or severe. The aim of this study was to investigate the serologicalcharacteristics of five anti-HNA-2a sera. Three sera were implicated in TRALI events and two were from alloimmune-neonatal neutropenia (ANN) cases. Method: An Ab titer was established against neutrophils (PMNs) with high HNA-2a expression (>70%) using both the granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT). Two clones of CD177 (7D8 and MEM-166) were applied in the monoclonal antibody immobilization of granulocyte antigens assay (MAIGA). These same monoclonal antibodies (Mab) were used in blocking studies for epitope mapping, against PMNs from two individuals determined to have high (>70%) and two individuals with moderate (30-70%) HNA-2a expression. Results: Only 2/3 of TRALI associated sera and 1/2 of ANN sera were MAIGA positive (i.e. captured by the CD177 clones). The MAIGA negative sera (TW and AB) had higher titers. PMNs pre-treated with both MAIGA negative sera reduced subsequent 7D8 binding but only partially reduced MEM-166 binding. This suggests that the Abs in these two sera were directed to a site closer to the 7D8 epitope. Although sera TQ, TS and AS were captured by both MAb, pre-treament with TS did not block subsequent MAb binding. And TQ and AS only demonstrated partial blocking. PMNs pre-treated with these MAbs did not reduce subsequent binding of Abs from all 5 sera (data not shown). These data indicate that the Abs in the sera bound to HNA-2a at more epitopes than the two tested. Conclusions: These data did not identify any characteristic that differentiated ANN from TRALI implicated Abs. They revealed differences in GIFT and GAT titers, and significant serological and epitope preference variability. These serological differences in characteristics may influence the severity of antibody mediated events such as TRALI. These observations justify further studies to characterize Abs implicated in TRALI events, such as Ab titers, isotype, subtypes and epitope reactivity.

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