The Influence of Inflammation on Mental Health

How a new clinical trial using CyTOF could change treatment options for depression

Mass cytometry assists research on role of immune system in disorders

A novel approach to finding effective treatments for psychiatric and neurodegenerative disorders is underway. Lori Turner, PhD, works as a postdoc in the NIHR Cambridge BRC Cell Phenotyping Hub and Department of Psychiatry at the University of Cambridge. As an immunologist with a background in host-pathogen interactions, she explores immune system function and dysregulation in various psychiatric disorders.

Currently, Lori is coordinating the biomarker studies in a clinical trial as part of the Wellcome Trust Consortium for the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA). Rather than target the nervous system, as do many current medicines for depression and neurodegeneration, the NIMA consortium is focused on the immune system. Several studies have already linked the immune system to psychiatric and neurodegenerative disorders, revealing increased levels of inflammation in patients with depression1,2 and Alzheimer’s disease3. By bringing together academia and pharmaceutical companies, NIMA investigates whether targeting the immune system could become an effective alternative treatment.

Immune cell biomarkers in depression

Certain immune cell subsets are increased in depression while others are decreased, and these changes relate to the level of severity of specific symptoms. Turner is investigating whether new treatments could influence these changes and subsequently affect symptoms. “With depression, some people feel anxiety or fatigue for example, and some people don’t—we see a spectrum of symptoms. We believe that different symptoms correlate with numbers of certain immune cells and changes occurring in these cells. This is what we’ve set out to identify,” explains Turner.

In the phase 2 clinical trial, the research team is testing an anti-inflammatory that crosses the blood- brain barrier to block activity of the P2X7 receptor, present on various immune cells and linked to stress- related depression. The group will perform immune profiling by mass cytometry to monitor the immune system before, during and after treatment. With any observed response, further study could identify immune biomarkers related to that response. Patients will also complete additional blood tests, questionnaires and magnetic resonance imaging brain scans throughout the trial to more comprehensively understand anti-inflammatory effects on the immune system and the brain.

Neuro-immunophenotyping with CyTOF

Turner came into mass cytometry through her work with the flow cytometry core facility at Cambridge. While her early research used flow cytometry, her more recent work at the Cambridge Biomedical Research Centre (BRC), part of the National Institute for Health Research (NIHR), requires larger panels that can only be analyzed by CyTOF® mass cytometry technology. In the first phases of the study, Turner directed preclinical work to assess depressed participants and healthy controls by mass cytometry, using the Fluidigm customizable human immune monitoring kit. Initial data focused on the P2X7 receptor and potential associated biomarkers.

For the clinical trial, the team moved to the Maxpar® Direct™ Immune Profiling Assay™. “Since standardization is extremely important for a multi-site clinical trial, we needed a pre-validated, as-is kit that included the markers we were focused on and that could be used across multiple sites since the trial will be carried out across five centers in the UK,” says Turner. “The idea of being able to add a whole blood sample directly to a pre-prepared assay tube, reducing site-to-site variation, was a huge factor for us. And the inclusion of Maxpar Pathsetter™ software allows us to quickly generate a report that goes into our online database, which is then shared with the clinical team for complete quality control.”

As the trial moves forward, the group is optimistic about the opportunity to identify related biomarkers that indicate response to the treatment. Good results could then initiate an expanded trial with more and different types of participants. Turner notes that the Maxpar Direct Immune Profiling Assay and Maxpar Pathsetter software can evolve with the study, allowing addition of new markers to investigate other aspects of immune cell subsets. For a list of this and other clinical trials employing mass cytometry, go to clinicaltrials.gov.

Learn more about the award-winning Maxpar Direct Immune Profiling Assay and Maxpar Pathsetter software.

Read a multi-site study publication: Multi‐site reproducibility of a human immunophenotyping assay in whole blood and peripheral blood mononuclear cells preparations using CyTOF technology coupled with Maxpar Pathsetter, an automated data analysis system

View results and download white paper: Deep Immune Profiling with the Maxpar Direct Immune Profiling System

Download poster: The Maxpar Direct Immune Profiling Assay and Maxpar Pathsetter Analysis



References:

  1. Chamberlain, S. et al. “Treatment-resistant depression and peripheral C-reactive protein.” British Journal of Psychiatry 214 (2019): 11–19. doi:10.1192/bjp.2018.66
  2. Lynall, M. et al. “Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression.” bioRxiv (2019): doi: 10.1101/706309
  3. Hakobyan, S. et al. “Complement biomarkers as predictors of disease progression in Alzheimer’s disease.” Journal of Alzheimer's Disease 54 (2016): 707–716

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