1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-specific Cell-mediated Immunity in SOT and HSCT Immunocompromised Patients
Session: Poster Abstract Session: Viruses and Bacteria in Immunocompromised Patients
Friday, October 5, 2018
Room: S Poster Hall
Background: Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of uncontrolled CMV reactivation and associated complications in both solid-organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy. We demonstrate here the suitability of a novel IFN-γ ELISpot assay (T-Track® CMV), based on the stimulation of PBMC with pp65 and IE-1 CMV proteins, to monitor CMV-CMI in SOT and HSCT patients.

Methods: Two independent prospective, longitudinal, observational, multicenter studies were conducted: in 86 intermediate-risk (D-/R+, D+/R+) renal transplant recipients (completed), and in 175 intermediate- or high-risk (D+/R+, D+/R-, D-/R+) HSCT recipients (ongoing). In both studies, patients underwent pre-emptive antiviral therapy. CMV-CMI, CMV load and clinical complications were monitored over ~six months post-transplantation.

Results: In the kidney transplantation setting, 95% and 88-92% of IFN-γ ELISpot test results were positive pre- and post-transplantation, respectively. CMV-specific response was reduced following immunosuppressive therapy and increased in patients with graft rejection, indicating the ability of the assay to monitor the patients’ immunosuppressive state. Interestingly, median pp65-specific response was 9-fold higher in patients with self-clearing viral load compared to antivirally-treated patients prior to first detection of CMV (MWU; p<0.001), suggesting that reactivity to pp65 is a potential immunocompetence marker. In HSCT patients, interim data analysis indicates that pp65-specific CMI measured after resolution of a primary CMV reactivation (requiring antiviral treatment) is a fair predictor of occurrence of recurrent CMV reactivation. Out of 71 patients (25 D+/R+, 3 D+/R-, 43 D-/R+) who experienced a primary CMV reactivation, 27 encountered a recurrent CMV reactivation. Interestingly, 39/44 (89%) patients free of recurrent reactivation had a positive pp65-specific test result following primary CMV reactivation.

Conclusion: Altogether, this novel IFN-γ ELISpot assay is a highly sensitive immune-monitoring tool with a potential use for the risk assessment of CMV-related clinical complications after SOT and HSCT.

Bernhard Banas, MD1, Dominik Steubl, MD2, Lutz Renders, MD2, Dominik Chittka, MD1, Miriam Banas, MD1, Thomas Wekerle, MD3, Martina Koch, MD4, Oliver Witzke, MD5, Monika Lindemann, MD5, Anja Muehlfeld, MD6, Claudia Sommerer, MD7, Antja Habicht, MD8, Christian Hugo, MD9, Thomas Huenig, MD10, Stephan Mielke, MD10, Martin Schreder, MD10, Eva Wagner, MD11, Daniel Teschner, MD11, Stefan Klein, MD12, Daniela Heidenreich, MD12, Sebastian Kreil, MD12, Kerstin Schaefer-Eckart, MD13, Johannes Gaertner, MD13, Mareike Verbeek, MD2, Sandra Grass, MD2, Christine Wolschke, MD4, Dietlinde Janson, MD4, Guido Kobbe, MD14, Mustafa Kondakci, MD14, Markus Ditschkowski, MD5, Tanja Gromke, MD5, Inken Hilgendorf, MD15, Marie Von Lilienfeld-Toal, MD15, Traudel Schmidt, PhD16, Anne Rascle, PhD16, Sascha Barabas, PhD16, Ludwig Deml, PhD16, Ralf Wagner, PhD1,16, Bernhard Kraemer, MD12, Bernd Krueger, MD12 and Daniel Wolff, MD1, (1)University Medical Center Regensburg, Regensburg, Germany, (2)Klinikum rechts der Isar TU Munich, Munich, Germany, (3)Medical University of Vienna, Vienna, Austria, (4)UKE University Medical Center Hamburg-Eppendorf, Hamburg, Germany, (5)University Hospital Essen, Essen, Germany, (6)Uniklinik RWTH Aachen, Aachen, Germany, (7)University Hospital Heidelberg, Heidelberg, Germany, (8)LMU Medical Center Munich, Munich, Germany, (9)University Medical Center Dresden, Dresden, Germany, (10)University Medical Center Wuerzburg, Wuerzburg, Germany, (11)University Medical Center of the JGU Mainz, Mainz, Germany, (12)UMM University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany, (13)Klinikum Nord, Nuernberg, Germany, (14)University Medical Center Duesseldorf, Duesseldorf, Germany, (15)University Hospital Jena, Jena, Germany, (16)Lophius Biosciences, Regensburg, Germany

Disclosures:

B. Banas, Lophius Biosciences: Investigator , Research support .

D. Steubl, Lophius Biosciences: Investigator , Research support .

L. Renders, Lophius Biosciences: Investigator , Research support .

D. Chittka, Lophius Biosciences: Investigator , Research support .

M. Banas, Lophius Biosciences: Investigator , Research support .

T. Wekerle, Lophius Biosciences: Investigator , Research support .

M. Koch, Lophius Biosciences: Investigator , Research support .

O. Witzke, Lophius Biosciences: Investigator , Research support .

M. Lindemann, Lophius Biosciences: Investigator , Research support .

A. Muehlfeld, Lophius Biosciences: Investigator , Research support .

C. Sommerer, Lophius Biosciences: Investigator , Research support .

A. Habicht, Lophius Biosciences: Investigator , Research support .

C. Hugo, Lophius Biosciences: Investigator , Research support .

T. Huenig, Lophius Biosciences: Investigator , Research support .

S. Mielke, Lophius Biosciences: Investigator , Research support .

M. Schreder, Lophius Biosciences: Investigator , Research support .

E. Wagner, Lophius Biosciences: Investigator , Research support .

D. Teschner, Lophius Biosciences: Investigator , Research support .

S. Klein, Lophius Biosciences: Investigator , Research support .

D. Heidenreich, Lophius Biosciences: Investigator , Research support .

S. Kreil, l: Investigator , Research support .

K. Schaefer-Eckart, Lophius Biosciences: Investigator , Research support .

J. Gaertner, Lophius Biosciences: Investigator , Research support .

M. Verbeek, Lophius Biosciences: Investigator , Research support .

S. Grass, Lophius Biosciences: Investigator , Research support .

C. Wolschke, Lophius Biosciences: Investigator , Research support .

D. Janson, Lophius Biosciences: Investigator , Research support .

G. Kobbe, Lophius Biosciences: Investigator , Research support .

M. Kondakci, Lophius Biosciences: Investigator , Research support .

M. Ditschkowski, Lophius Biosciences: Investigator , Research support .

T. Gromke, Lophius Biosciences: Investigator , Research support .

I. Hilgendorf, Lophius Biosciences: Investigator , Research support .

M. Von Lilienfeld-Toal, Lophius Biosciences: Investigator , Research support .

T. Schmidt, Lophius Biosciences: Employee , Salary .

A. Rascle, Lophius Biosciences: Employee , Salary .

S. Barabas, Lophius Biosciences: Employee and Shareholder , Salary .

L. Deml, Lophius Biosciences: Employee and Shareholder , Salary .

R. Wagner, Lophius Biosciences: Board Member and Shareholder , Consulting fee .

B. Kraemer, Lophius Biosciences: Investigator , Research support .

B. Krueger, Lophius Biosciences: Investigator , Research support .

D. Wolff, Lophius Biosciences: Investigator , Research support .

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.