Oliver A Cornely - assoc. RG

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).


Prof. Dr. Oliver A Cornely

Clinical Trials Center Cologne (CTCC)

Prof. Dr. Oliver Cornely

assoc. CMMC Research Group

oliver.cornely@uk-koeln.de

Publications - Oliver A Cornely

Link to PubMed

FIGURE 1 Imaging studies of Candida spondylodiscitis and paravertebral abscess. (A) Positron emission tomography computer tomography with [18F] 2-fluoro-desoxy-d-glucose (FDG-PET/CT) shows pathological FDG uptake in the l3-l4 vertebrae including the left psoas muscle (white arrows), as well as bone destruction (grey arrow). (B) From left to right: sagittal, coronal and axial magnetic resonance imaging (MRI) of the lumbar spine revealed abnormal signal/enhancement of the L3-4 vertebral marrow (black arrow) including intervertebral space and paraspinal soft tissues (white arrow) indicative for spondylodiscitis and adjacent psoas abscess. From Koehler FC et al. Mycoses 2017
FIGURE 2 Detection of Candida albicans reactive T cells. Cell frequencies (%) and absolute cell (n) count are given. Candida albicans reactive T cells at baseline, at 4 and 12 months. CD69-CD154 double-expression of Candida albicans reactive CD4+ T cells after antigen stimulation with Candida albicans lysate. From Koehler FC et al. Mycoses 2017