Background: The nature of the immune response to seasonal Influenza A Virus infection has not been well characterized in transplant patients. Antibodies may be directed against conserved or variable regions of the virus. The objective of our study was to perform a detailed characterization of influenza-specific antibody responses using a high-throughput based array platform.

Methods: Serum was collected at onset of Influenza A infection (day 0) and convalescence (day 28) from transplant patients with microbiologically confirmed influenza infection. Our antigen library included a diverse collection of 92 influenza antigens, including hemagglutinin (HA), neuraminidase (NA) and conserved influenza antigens of various influenza subtypes, host origins and geographical locations. Antigens were printed onto nitrocellulose-coated slides to construct an influenza protein array. These arrays were probed using patient sera and fluorescently conjugated IgG and IgM secondary antibodies. Antibody responses to each antigen were determined by measurement of median fluorescent intensity (MFI).

Results: A total of 100 transplant patients with influenza A infection were assessed (80 SOT; 20 HSCT). Severe disease was defined as pneumonia at presentation (N=24) or need for mechanical ventilation (N=9). Significant heterogeneity in baseline and convalescent antibody diversity was observed between patients. However, SOT patients consistently produced significantly more anti-influenza IgM and IgG antibodies relative to HSCT patients and these responses were primarily directed toward HA and NA antigens. For a subset of antigens, evidence of differential antibody responses was observed in patients who had more severe disease manifestations. For example, in patients with pneumonia, antibodies against a small subset of H3N2 and H1N1 antigens were significantly greater at presentation, while a subset of antibodies, primarily targeting HA, were lower than the group without pneumonia. By day 28, significant increases in antibodies directed against a number of antigens were observed for many patients. However, patients who required mechanical ventilation had higher IgG antibody levels that targeted HA (especially H1N1 HA) than those without mechanical ventilation.

Conclusions: Transplant patients form diverse antibody responses to influenza infection including those to conserved flu antigens. Significant heterogeneity and differences in antigen specificity are evident and may have clinical correlates.

CITATION INFORMATION: Ferreira V, Chruscinski A, Han S, Humar A, Kumar D. Diversity of Influenza Antibody Repertoire in Transplant Recipients with Natural Influenza Infection. Am J Transplant. 2016;16 (suppl 3).

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