Selected artcles December 2015
New ways of targeting antigen to dendritic cells
Enhanced Humoral Responses Induced by Targeting of Antigen to Murine Dendritic Cells
L. H. Pugholm, L. R. Petersen, E. K. L. Søndergaard, K. Varming and R. Agger
The December issue of Scandinavian Journal of Immunology contains two papers from a Danish group at Aalborg University, covering different aspects of the same topic – namely targeting of antigens to dendritic cells. The first paper comprise an in vivo targeting study investigating a panel of different targets. The second paper describes an in vitro targeting assay that confirmed the results obtained in the in vivo targeting study, which enable this assay to be chosen as at first-line evaluation of potential targets.
Lotte Hatting Pugholm was a PhD student at Laboratory of Immunology, Aalborg University and at Department of Clinical Immunology, Aalborg University Hospital at the time these studies were undertaken. Now she is a post doc in a research group at the Department of Clinical Immunology at the Aalborg University Hospital.
– The work was done during my PhD, thus I was responsible for planning and performing all or the majority of the work related to the data, she says.
In addition, Lotte Hatting Pugholm drafted the manuscripts but the study design was a joint decision.
The main findings in the in vivo study was that targeting of antigen to dendritic cells can induce strong humoral responses against an otherwise weak antigen, even without addition of adjuvant and that inherent properties of the targeting antibodies are of great importance for the outcome. The in vitro study demonstrated that it is possible to obtain comparable results by the presented in vitro screening assay.
Lotte Hatting Pugholm like the work that led to these publication
– I especially enjoyed working with laboratory mice. In addition, setting up the ELISA test for investigation of the humoral response was interesting. The fact that we looked for mouse IgG antibodies directed against rat IgG made the ELISA setup more complicated than usual and needed several steps of optimization, she concludes.
Investigations on the role of FURIN in plasma
The Plasma Level of Proprotein Convertase FURIN in Patients with Suspected Infection in the Emergency Room: A Prospective Cohort Study
N. Ranta, H. Turpeinen, A. Oksanen, S. Hämäläinen, R. Huttunen, R. Uusitalo-Seppälä, E. Rintala, J. Aittoniemi and M. Pesu
In a prospective cohort study, performed by researchers from University of Tampere, FURIN levels in plasma from 537 patients was determined using ELISA. The patients were admitted to the emergency room with suspected infection.
FURIN belongs to the family of proprotein convertases, is widely expressed and regulates the maturation of numerous precursor protein such as growth factors, enzymes, hormones, cytokines and much more. In addition, it is also involved in the pathogenesis of several diseases.
The group in Finland have previously shown that FURIN is upregulated upon the activation of both T lymphocytes and innate immune cells, and others have demonstrated many pathogens are activated through FURIN/PCSK dependent proteolysis. However, whether the FURIN levels in plasma are also upregulated upon immune activation had not previously been studied.
– We hypothesized that patients with infections might have unregulated plasma FURIN levels, but we found that, at least with the method we used, elevated plasma FURIN does not associate with infections or predict patient survival, says Marko Pesu, principal investigator and Associate Professor at the University of Tampere.
In contrast, patients that had rheumatic disease had significantly more often elevated plasma levels of FURIN. Thus, it might be that plasma FURIN is not a good marker for infections, but it could be beneficial in the diagnostics of autoimmune diseases.
– Of course more work is needed, because the patient cohort we used was not collected to study autoimmunity, says Marko Pesu who was also not very happy about the sensitivity of the FURIN measurement.
Nevertheless, Marko Pesu was glad to see that observations from basic research, i.e. FURIN up-regulation inside immune cells might be beneficial for future diagnostics in rheumatoid diseases.
– It was also fruitful to collaborate with doctors who work with infectious patients.
In the future, Marko Pesu and his group would like to continue evaluation plasma FURIN levels in different patient cohorts, especially those with autoimmunity, given a more sensitive method for FURIN detection is available.
