Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Donor-specific anti-HLA antibodies (DSA) represent an important biomarker for acute rejection and are a major cause of long-term graft failure after kidney transplantation (KTx). The immunological mechanisms that lead to the development of DSA are not entirely understood. Our previous results obtained in a cohort of KTx recipients receiving Thymoglobulin induction showed an imbalance between circulating Th1-TFH and TREG, which correlated with the development of DSA. Here we measured the levels of IL-12p70, IL-6 and IL-21 pro-inflammatory cytokines that drive TFH cell responses and characterized the memory phenotype and function of circulating Th1-TFH cells from the same cohort of patients.
Twenty-nine Thymoglobulin-induced KTx patients participating in an ongoing prospective study were monitored for DSA occurrence in the first year after Tx. During this period, 8 patients were identified as DSA+, while 8 DSA- KTx recipients and 5 healthy subjects (HC) were included as controls. Whole blood and plasma were obtained at regular intervals and analyzed for cytokine production and phenotypes.
Our results showed that patients who developed DSA had higher pre-Tx levels of IL-12p70, IL-6 and IL-21 in plasma as compared to DSA- patients (mean±SD pg/ml: 64±31vs 27±25 p<0.03; 67±98 vs 25±34 p<0.05*; 183±211 vs 54±33 p<0.01). In addition, IL-17 and IFN-γ were also elevated in pre-Tx plasma samples from DSA+ patients (89±29 vs 40±33 p<0.01; 43±25 vs 22±21). Interestingly, at the time of DSA occurrence, circulating Th1-TFH cells from DSA+ patients displayed higher % of effector memory (EM) phenotypes and increased IFN-γ and IL-21 production (n=2), as compared to pre-Tx values, DSA- KTx recipients (n=2) and HC (n=2).
In conclusion, patients who developed DSA displayed pre-Tx increased levels of pro-inflammatory cytokines that may skew lymphopenia induced proliferation and T cell repopulation after Thymoglobulin induction towards TFH cells with EM phenotypes. This in turn may allow circulating TFH cells increased chances to become activated by allo-antigens, and provide cognate help to B cells for DSA generation after KTx.
To cite this abstract in AMA style:Macedo C, Hadi K, Elinoff B, Marrari M, Zeevi A, Ramaswami B, Chalasani G, Shields A, Alloway R, Woodle E, Lakkis F, Metes D. Pre-Transplant Levels of TFH cell-Inducing Pro-Inflammatory Cytokines Correlate With DSA Formation After Kidney Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/pre-transplant-levels-of-tfh-cell-inducing-pro-inflammatory-cytokines-correlate-with-dsa-formation-after-kidney-transplantation/. Accessed December 3, 2020.
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