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Clinical Rejection-Risk Assessment with Allospecific CD154+T-Cytotoxic Memory Cells (CD154+TcM) After Pediatric Liver or Intestine Transplantation (LTx, ITx).

K. Soltys, G. Bond, G. Mazariegos, L. O'Toole, C. Trautz, L. Remaley, A. Zeevi, C. Ashokkumar, R. Sindhi.

Surgery, Children's Hosp of Pgh of UPMC & Univ of Pittsburgh, Pittsburgh, PA.

Meeting: 2016 American Transplant Congress

Abstract number: 140

Keywords: Intestinal transplantation, Liver transplantation, Pediatric, T cell reactivity

Session Information

Date: Sunday, June 12, 2016

Session Name: Concurrent Session: Liver: Immunosuppression and Rejection

Session Time: 4:30pm-6:00pm

 Presentation Time: 4:42pm-4:54pm

Location: Room 312

Related Abstracts
  • Clinical Utility of Allospecific CD154+T-Cells in Children With Liver Or Intestine Transplantation (LTx, ITx)
  • CMV-Specific CD154+T-Cells and CMV Disease Status After Liver Or Intestine Transplantation (LTx, ITx)

Background: In preclinical evaluation, CD154+TcM predict acute cellular rejection after LTx or ITx with sensitivity/specificity of 80%. Purpose/Methods: To summarize test indications and performance during clinical use in the first 180 children with LTx or ITx. Rejection-risk is increased in this cell-culture-based assay leading to a positive test, if donor-specific CD154+TcM are increased 1.1-fold or more over non-specific alloreactive CD154+TcM. Results: Of 180 children sampled at least once, 10 were excluded because steroids were escalated for presumed rejection before sampling. For the remaining 170 children, median age was 12 years (0.6-21), gender M: F was 92: 78, transplant type LTx: ITx: combined LTx-ITx was 129: 14: 27. Testing occurred at median 2298 days (range 8-7568) after transplantation and coincided with allograft dysfunction or surveillance. Fifty children demonstrated rejection on biopsy (n=44) or clinically (n=6) and 130 children did not in the 60 day post-sampling period. Test sensitivity, specificity, positive and negative predictive values and respective 95% confidence intervals for predicting rejection were 78% (64-88), 85% (77-91), 68% (55-80) and 90% (83-95), respectively. False positive tests were associated with blood sampling significantly later after transplantation (3141+/-1923 vs 1534+/-1529 days, p=0.002) and lower Tacrolimus whole blood concentrations (4.1+/-3.2 vs 8.3+/-6.3, p=0.01) compared with true positive tests. In logistic regression analysis relating CD154+TcM to rejection, the timing of sample after transplantation emerged as a significant covariate. Test predictions concurred with rejection/non-rejection outcomes in a) children with and without EBV viremia (41/50 or 82% vs 37/53 or 70%, p=0.173, NS), b) all five LTx recipients with allograft cholangitis and all three ITx recipients with allograft enteritis, c) a child with CMV viremia 9800 copies/ml. Conclusions: Clinical rejection-risk assessment of pediatric LTx and ITx with allospecific CD154+TcM confirms clinically acceptable test performance observed during preclinical evaluation and is unaffected by common transplant viruses and allograft cholangitis or enteritis. Enhanced rejection risk in stable long-term allograft recipients on low immunosuppression merits follow-up to establish clinical relevance.

CITATION INFORMATION: Soltys K, Bond G, Mazariegos G, O'Toole L, Trautz C, Remaley L, Zeevi A, Ashokkumar C, Sindhi R. Clinical Rejection-Risk Assessment with Allospecific CD154+T-Cytotoxic Memory Cells (CD154+TcM) After Pediatric Liver or Intestine Transplantation (LTx, ITx). Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Soltys K, Bond G, Mazariegos G, O'Toole L, Trautz C, Remaley L, Zeevi A, Ashokkumar C, Sindhi R. Clinical Rejection-Risk Assessment with Allospecific CD154+T-Cytotoxic Memory Cells (CD154+TcM) After Pediatric Liver or Intestine Transplantation (LTx, ITx). [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/clinical-rejection-risk-assessment-with-allospecific-cd154t-cytotoxic-memory-cells-cd154tcm-after-pediatric-liver-or-intestine-transplantation-ltx-itx/. Accessed March 6, 2021.

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