Intracellular IFNgamma production in CD3 negative cells exposed to allo-antigens is an indicator of prior sensitization

Transplant Immunology
Mieko ToyodaS C Jordan

Abstract

Sensitization to HLA antigens (Ags) is a significant obstacle to kidney transplantation and risk factor for antibody-mediated rejection (AMR). Current screening methods to assess HLA Ag exposure include various antibody assays. However, tools to accurately measure cell-mediated immunity to allo-Ags in a clinical setting are lacking. Here we report on an intracellular cytokine flow cytometry (CFC) assay that detects intracellular gamma-interferon (IFNgamma) production in non-T cell populations (CD3-) that appears to assess sensitization from previous allo-Ag exposure. Blood from 106 highly-HLA sensitized (HS) patients (pre-, post-IVIG-treatment [Rx] and/or post-transplant) and 14 3(rd) party normal controls (3(rd)N) were incubated with donor or 3(rd)N peripheral blood mononuclear cells (PBMCs), and IFNgamma+/CD3- cells were enumerated. The percentage of IFNgamma+ cells in CD3- cells without stimulation in pre-IVIG-Rx HS patients was similar to normals, but significantly increased with incubation with donor and/or 3(rd)N PBMCs. Reactivity in normals was minimal. Reactivity was higher in HS females than HS males. Normal females with previous pregnancy (PG) showed significantly higher response than females without PG or non-sensiti...Continue Reading

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Citations

Mar 29, 2011·Clinical Journal of the American Society of Nephrology : CJASN·Kwaku MarfoEnver Akalin
Jan 18, 2012·Pediatric Transplantation·Stanley C Jordan
Oct 20, 2012·Expert Review of Clinical Immunology·Stanley C Jordan
May 29, 2015·Transplantation·Thomas ReschKatja Kotsch

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