By studying the single nucleotide polymorphisms (SNPs) of FCGR2A and FCGR3A, genes encoding FcγR, we previously demonstrated the significantly higher incidence of blood stream infections (BSI) in the FCGR3A [158F/V or F/F] (distinguished by its low IgG3 affinity) than the FCGR3A [158V/V] individuals of living-donor liver transplant (LT) recipients. Since NK cells and macrophages are both capable of inducing ADCC via FcγRIIIa, adoptive immunotherapy with activation of those immunocytes may compensate for the genetic susceptibility to post-transplant BSI. The present study investigated the preventing effect of adoptive immunotherapy with activated liver allograft-derived lymphocytes on BSI after LT. Liver lymphocytes isolated from the effluent perfusates of liver allografts were cultured with IL-2 for 3 days, and anti-CD3 mAb was added 12 hours before the infusion in order to opsonize the CD3⁺ fraction. 3 days after LT, the activated liver NK cell/macrophage-enriched lymphocytes were administered through venous circulation to 24 LT patients with the FCGR3A [158F/F or F/V] SNP. Forty-eight patients with the FCGR3A [158F/F or F/V] SNP that underwent LT but did not receive adoptive immunotherapy served as a control. A tendency towards lower BSI incidence and significantly improved survival were observed in the patients with adoptive immunotherapy compared to those who did not receive the therapy (BSI ratio: 8.3% vs. 29.2%; p = 0.07, 1-year survival: 91.7% vs. 79.2%; p = 0.031). The predominant causative pathogen of BSI in the patients without immunotherapy was gram-positive cocci (GPC), of which one third was MRSA, whereas that in the patients with immunotherapy was gram-negative rods (GNR). Unlike GNR, the components in the GPC cell wall can be directly targeted by IgG in the human sera, resulting in ADCC-mediated recognition through FcγRs. This may explain the association between the causative pathogen of BSI and FCGR3A SNP. The FCGR3A SNP in donors didn't influence the effects of immunotherapy on the BSI incidence, probably because of ex vivo forcible activation of donor-lymphocytes prior to inoculation. In conclusion, adoptive immunotherapy with activated liver allograft-derived lymphocytes ameliorated the susceptibility to post-transplant BSI associated with the FCGR3A SNP.

CITATION INFORMATION: Ohdan H, Ohira M, Shimizu S, Tanaka Y, Tahara H, Ide K, Ishiyama K, Kobayashi T. Adoptive Immunotherapy with Liver Allograft-Derived Lymphocytes Compensate for the Susceptibility to Post-Liver Transplant Blood Stream Infection Associated with FCGR3A SNP. Am J Transplant. 2017;17 (suppl 3).

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