Center for Molecular Medicine Cologne

Cornely, Oliver A - assoc. RG 28

Antigen reactive CD69+/CD154+/CD4+ T Cells for Cell mediated Immunity in Infectious Diseases - TCI – ID

Abstract

In patients, a variety of risk factors predispose for different invasive fungal infections. Common invasive fungal infections are invasive candidiasis, invasive aspergillosis, and mucormycosis. Patients with well-defined profound immunosuppression are at high risk for invasive aspergillosis and mucormycosis, whereas invasive candidiasis occurs in immunocompetent patients, too.
Current standard diagnostics for invasive fungal infections such as blood culture, bronchoalveolar lavage, tissue biopsies and serological assays are sensitive to errors, sometimes unspecific, invasive and often contraindicated. The lack of reliable diagnostics along with high mortality lead to complex treatment strategies by means of prophylaxis, fever-driven, diagnosis-driven, and targeted treatment approaches.
With the development of the antigen-reactive T cell assay a non-invasive diagnostic allows fast and valid identification of pathogens to genus and species level when standard tests remain negative or patients’ comorbidities forbid invasive diagnostics.
We use peripheral blood mononuclear cells (PBMCs) from patients’ full blood and challenge them with fungal lysates. If the PBMCs encounter a repetitive fungal challenge, we identify fungus-reactive CD4+ T cells in the patient’s blood via flow cytometry.
The current project is advanced to further bacterial and fungal pathogens for clinical diagnostics and to investigate the cellular immune response in cooperation with the AG Klinische Mikrobiomforschung (PD Dr. M. Vehreschild) and AG Immunologie der HIV-Infektion (PD Dr. C. Lehmann).

Clinical/medical relevance and sustainability in disease understanding

Invasive fungal infections are associated with high morbidity and mortality in immunosuppressed and immunocompetent patients. With the development of new diagnostic tools, we want to overcome the problem of false negative standard diagnostics to facilitate targeted treatment and thus improve patient outcome.We receive patient samples from multiple sites in Germany through our FungiResearch network (http://fungiresearch.uni-koeln.de) and act as the lab of the European Excellence Center of Medical Mycology (https://www.ecmm.info).

  • Aguilar RC, Salmanton-Garcia J, Carney J, Boll B, Kochanek M, Jazmati N, Cornely OA, and Vehreschild M (2020). Clostridioides difficile infections in the intensive care unit: a monocentric cohort study. Infection 48, 421-7.
     
  • Augustin M, Schommers P, Suarez I, Koehler P, Gruell H, Klein F, Maurer C, Langerbeins P, Priesner V, Schmidt-Hellerau K, Malin JJ, Stecher M, Jung N, Wiesmuller G, Meissner A, Zweigner J, Langebartels G, Kolibay F, Suarez V, Burst V, Valentin P, Schedler D, Cornely OA, Hallek M, Fatkenheuer G, Rybniker J, and Lehmann C (2020). Rapid response infrastructure for pandemic preparedness in a tertiary care hospital: lessons learned from the COVID-19 outbreak in Cologne, Germany, February to March 2020. Euro Surveill 25.
     
  • Bacher P, Rosati E, Esser D, Martini GR, Saggau C, Schiminsky E, Dargvainiene J, Schroder I, Wieters I, Khodamoradi Y, Eberhardt F, Vehreschild M, Neb H, Sonntagbauer M, Conrad C, Tran F, Rosenstiel P, Markewitz R, Wandinger KP, Augustin M, Rybniker J, Kochanek M, Leypoldt F, Cornely OA, Koehler P, Franke A, and Scheffold A (2020). Low-Avidity CD4(+) T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19. Immunity 53, 1258-71 e5.
     
  • Cornely FB, Cornely OA, Salmanton-Garcia J, Koehler FC, Koehler P, Seifert H, Wingen-Heimann S, and Mellinghoff SC (2020). Attributable mortality of candidemia after introduction of echinocandins. Mycoses 63, 1373-81.
     
  • Salmanton-Garcia J, Koehler P, Kindo A, Falces-Romero I, Garcia-Rodriguez J, Racil Z, Chen SC, Klimko N, Desoubeaux G, Thompson Gr, III, Benitez-Penuela MA, Rodriguez JY, Sheppard DC, Hoenigl M, Le Govic Y, Badali H, Baddley JW, Chander J, Ingram PR, Pakstis DL, Mellinghoff SC, Atici S, Cesaro S, Chakrabarti A, Dupont D, Gonzalez GM, Hatvani L, Herbrecht R, Klyasova G, Lass-Florl C, Mares M, Mullane K, Vinh DC, Wisplinghoff H, Lackner M, Cornely OA, Seidel D, and group EIw (2020). Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScope()-Global Registry for Emerging Fungal Infections. The Journal of infection 81, 802-15.
     
  • Schommers P, Gruell H, Abernathy ME, Tran MK, Dingens AS, Gristick HB, Barnes CO, Schoofs T, Schlotz M, Vanshylla K, Kreer C, Weiland D, Holtick U, Scheid C, Valter MM, van Gils MJ, Sanders RW, Vehreschild JJ, Cornely OA, Lehmann C, Fatkenheuer G, Seaman MS, Bloom JD, Bjorkman PJ, and Klein F (2020). Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell 180, 471-89 e22.
     
  • Schumacher S, Salmanton-Garcia J, Cornely OA, and Mellinghoff SC (2020). Increasing influenza vaccination coverage in healthcare workers: a review on campaign strategies and their effect. Infection 10.1007/s15010-020-01555-9.
     
  • Sprute R, Salmanton-Garcia J, Sal E, Malaj X, Falces-Romero I, Hatvani L, Heinemann M, Klimko N, Lopez-Soria L, Meletiadis J, Shruti M, Steinmann J, Seidel D, Cornely OA, and Stemler J (2020b). Characterization and outcome of invasive infections due to Paecilomyces variotii: analysis of patients from the FungiScope(R) registry and literature reports. J Antimicrob Chemother 10.1093/jac/dkaa481.
Prof. Dr. Oliver A Cornely CMMC Cologne
Prof. Dr. Oliver A Cornely

CECAD / Clinical Trials Center Cologne

+49 221 478 6494

+49 221 478 86465

CECAD / Clinical Trials Center Cologne

Gleueler Str. 269

50935 Cologne

http://www.cecad.uni-koeln.de/translational-research/clinical-trials/

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Publications - Oliver A Cornely

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