Projects Biomarkers for Infectious Diseases

Projects Biomarkers for Infectious Diseases

Cerebrospinal biomarkers for early diagnosis and risk stratification of CNS infections

Infections of the CNS can often not be differentiated well from non-infectious inflammatory diseases, and pathogen detection is variably efficient, depending on the assay / pathogen and on the time of lumbar puncture with respect to the onset of infection. In collaboration with the Dept. of Neurology (M. Stangel) and the MHH RCU Metabolomics and Mass Spectrometry (V. Kaever), we are therefore searching for cerebrospinal fluid small molecule (metabolic) biomarkers for risk stratification of patients with suspected infections of the CNS. As a pilot project we selected varicella-zoster virus (VZV) reactivation, as this disease may span the spectrum from mild segmental zoster (shingles) to life-threatening encephalitis. We are currently expanding our work to other chronic herpes viruses, notably HSV-1 (CMV is also envisaged, pending availability of samples). One strategic advantage of focusing on chronic herpesvirus infections is that there are excellent local opportunities to test the functional importance of any biomarker candidates by collaborating with research groups at MHH, TWINCORE and HZI working on the biology of these pathogens.

Publications

Predictive biomarkers for a poor immune response to influenza vaccination in elderly individuals

In the general population the risk of severe influenza infection, but also that of a poor vaccine response, are highest among the elderly. In this project we have therefore been collaborating with the CRC Core Facility (C. Schindler), the CRC Biobank (T. Illig), and the HZI Dept. of Vaccinology (C. Guzman) to identify biomarkers for a poor immune response to influenza vaccination in individuals older than 65 years. We performed a pilot study (n=34) in 2014-15 and a main study (n=200) in 2015-16. The resulting dual data set now allows computational validation of biomarker candidates. Thus far, we have identified two cytokines whose plasma concentrations, in both studies, are lower in the vaccine-nonresponders than in the responders. These results also suggest that raising levels of these cytokines in individuals with low levels may improve the vaccine response. Patent protection is being filed for using these cytokines as biomarkers and as interventions to improve the vaccine response.

Publications

Cerebrospinal biomarkers for early diagnosis and risk stratification of CNS infections

Kuhn M, Sühs KW, Akmatov MK, Klawonn F, Wang J, Skripuletz T, Kaever V, Stangel M, Pessler F. (2017) Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite signatures and biomarkers for CNS involvement in varicella zoster virus reactivation. J Biol Chem (under review).

Predictive biomarkers for a poor immune response to influenza vaccination in elderly individuals

Akmatov MK, Jentsch L, Riese P, May M, Ahmed MW, Werner D, Rosel A, Prokein J, Bernemann I, Klopp N, Prochnow B, Illig T, Schindler C, Guzman CA, Pessler F (2017) Motivations for (non)participation in population-based health studies among the elderly - comparison of participants and nonparticipants of a prospective study on influenza vaccination. BMC Med Res Methodol 17(1): 18.

Akmatov MK, Riese P, May M, Jentsch L, Ahmed MW, Werner D, Rosel A, Tyler M, Pessler K, Prokein J, Bernemann I, Klopp N, Prochnow B, Trittel S, Tallam A, Illig T, Schindler C, Guzman CA, Pessler F (2017) Establishment of a cohort for deep phenotyping of the immune response to influenza vaccination among elderly individuals recruited from the general population. Hum Vaccin Immunother 13(7): 1630-1639.