Translating neuroimmunology for innovation in clinical research and services
Project leader: Dr Adam Al-Diwani, NIHR Clinical Lecturer
Advances in understanding connections between the brain and immune system could provide new approaches to diagnosis and monitoring, and new treatments across cognitive and mental health (see Al-Diwani et al 2021).
A key example is the re-discovery of meningeal lymphatics. Drainage from this brain barrier into neck cervical lymph nodes (CLN) renders them a promising candidate site for sampling neuroimmune processes.
Working with radiology, Adam developed a ‘bedside to bench’ pipeline sampling CLNs using ultrasound-guide fine needle aspiration (FNA). The technique was safe and acceptable, and the sample distinct from blood and amenable to downstream modern tools, including flow cytometry and cell culture. Adam and his colleagues showed that patients with active, compared to resolved, autoimmune encephalitis had evidence of ongoing antigen-specific reactions in CLNs (Al-Diwani et al 2022 in Brain; video abstract available on Youtube).
However, several technical aspects of the samples remained unexplored as did the acceptability of the approach in broader clinical groups and healthy volunteers. Therefore, Adam is:
- together with vaccine immunologists, more deeply exploring cell populations with spectral flow cytometry and single-cell RNA sequencing to build a detailed map;
- via collaboration both locally and externally, exploring the proteomic landscape in the fluid phase of the sample;
- via the NIHR Oxford Health Biomedical Research Centre (BRC) and surveys of previous participants, exploring the acceptability and optimal delivery of the technique.
Finally, this is now extending to a larger bio-sampling project in the BRC molecular targets theme. Within this theme, we aim to collaborate with patients in real-world cognitive and mental health clinical settings to correlate neuroimmune signals with detailed symptom mapping.