Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: At ATC 2014, we demonstrated that detection of single nucleotide polymorphisms (SNP) of FcγRIIIa helps predict the susceptibility of liver transplant (LT) recipients to bloodstream infection (BSI) and in determining outcome following LT. Because NK cells induce ADCC via FcγRIIIa, adoptive immunotherapy with activated NK cells might ameliorate FcγRIIIa SNP-associated susceptibility to post transplant BSI.
Methods: We analyzed BSI incidence and its causative microorganism in 93 consecutive recipients within 30 days of and prognosis after primary living-donor LT. We also enrolled 39 adoptive-immunotherapy cases, which involves intravenously injecting LT recipients with activated NK cells isolated from perfusate effluents of liver allografts, to investigate BSI occurrence. FcγRIIIa [158F/V] SNP in the recipients and donors were determined using PCR-RFLP.
Results: The significantly higher incidence of BSI and the lower survival were observed in the patients with FcγRIIIa [158F/F or F/V] (n =48) when compared to those with FcγRIIIa [158V/V] (n=45) (BSI ratio: 29.2%vs8.9%; p=0.018, log-rank p=0.046). The predominant BSI pathogen in FcγRIIIa [158F/V or F/F] was gram-positive cocci (GPC) (68.8%), of which one third was methicillin-resistant Staphylococcus aureus, while that in FcγRIIIa [158V/V] was gram-negative rod (GNR) (66.7%). In a separate phase I trial on 39 liver cirrhosis patients with HCC or HCV, we successfully performed immunotherapy using activated liver allograft-derived NK cells to prevent HCC or HCV recurrence. Among them, BSI incidence was lower in the 24 FcγRIIIa [158F/V or F/F] patients than in the 48 FcγRIIIa [158F/V or F/F] patients from the cohort described earlier who received no immunotherapy (BSI ratio: 8.3% vs. 29.2%; p = 0.07, 1-year survival: 91.7% vs. 79.2%). Immunotherapy reduced GPC-associated BSI incidence (2 cases infected with GNR/2 patients with BSI). The FcgRIIIa SNP was also analyzed in 30 of the 39 eligible donors; however, the FcγRIIIa SNP in the donor didn't influence the effects of immunotherapy on the BSI incidence.
Conclusions: FcγRIIIa [158 F/F or F/V] was associated with the occurrence of the BSI caused by GPC following LT. Moreover, adoptive immunotherapy with activated NK cells, which highly express FcγRIIIa, can ameliorate the FcγRIIIa SNP-associated susceptibility of recipients to post transplant BSI due to GPC.
To cite this abstract in AMA style:Shimizu S, Tanaka Y, Tazawa H, Verma S, Ohdan H. Adoptive Immunotherapy Using Activated NK Cells Ameliorates the FcγRIIIa Gene Polymorphism-Associated Susceptibility to Post Transplant Bloodstream Infection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/adoptive-immunotherapy-using-activated-nk-cells-ameliorates-the-fcriiia-gene-polymorphism-associated-susceptibility-to-post-transplant-bloodstream-infection/. Accessed June 15, 2021.
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