Session Type: Poster Session
Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
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 cellular mechanisms that lead to the development of DSA are not entirely understood. Here we analyzed the phenotypic polarization and activation status of CXCR5+CD45RO+CD4+ circulating (c)T follicular helper cell (TFH), which are known to be involved in antibody production by B cells. We have consented 30 Thymoglobulin-induced KTx patients participating in an ongoing observational cross-sectional study. Nineteen patients were identified as DSA (MFI>1000) carriers, including 8 patients undergoing an acute antibody-mediated rejection (ABMR) and 11 patients with asymptomatic DSA. In addition, 6 patients were considered stable and DSA-, and 5 patients presented with an acute cellular rejection (ACR) only. Whole blood were obtained from patients with asymptomatic DSA or at the time of for cause biopsy and analyzed by flow cytometry to identify cTFH subsets: Th1 (CXCR3+), Th17 (CCR6+), Th1/Th17 (CXCR3+CCR6+) and Th2 (CXCR3–CCR6–) as well as the co-expression of activation markers PD1 and ICOS (PD1+/ICOS+).
Our results showed that although patients who developed DSA had similar levels (%) cTFH cells as compared to DSA- patients (mean ± STDV 17%±7.4 and 22.5%±10), they presented significantly higher activation markers (PD1+/ICOS+) on their Th1, Th1/Th17, and Th17 cTFH subtypes (9%±10.6 and 19.8%±16.4 p=0.05; 3.7%±4 and 17.8%±11 p<0.001; 2.3%±2.3 and 7.3%±5.6 p=0.04). In addition, ABMR KTx patients unlike those with ACR presented higher % cTFH cells (22.3%±8.6 and 9.7%±5.3; p=0.01) with higher PD1+/ICOS+ expression (14.2%±10.3 and 4.6%±4.4; p=0.06) which was observed in all 4 cTFH subsets (Th1, Th2, Th1/17, and Th17).
In conclusion, patients who developed either asymptomatic DSA or ABMR, unlike stable DSA- or ACR patients displayed activated cTFH cells that may directly provide allo-Ag specific cognate help to B cells for shaping DSA generation after KTx. Monitoring cTFH cell subsets may uniquely allow the development of novel diagnostic and predictive biomarkers for graft outcomes and tailored therapy in patients with DSA.
CITATION INFORMATION: Macedo C, Fadakar P, Hadi K, Ellinof B, Zeevi A, Hariharan S, Metes D. Activated Th1 and Th17 cTFH Phenotype Correlates with DSA Production in Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Macedo C, Fadakar P, Hadi K, Ellinof B, Zeevi A, Hariharan S, Metes D. Activated Th1 and Th17 cTFH Phenotype Correlates with DSA Production in Kidney Transplant Recipients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/activated-th1-and-th17-ctfh-phenotype-correlates-with-dsa-production-in-kidney-transplant-recipients/. Accessed June 26, 2022.
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