Title: Cervical lymph node aspirations: cellular and molecular phenotyping at an emerging neuro-immune nexus
Funder: The Academy of Medical Sciences

Abstract: The understanding of connections between the brain and immune system has expanded with relevance of this system in homeostasis, such as sleep, and perturbation in neuropsychiatric disorders like dementia. 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 neuro-immune processes. We recently used ultrasound-guided fine needle aspiration (FNA) of CLN to retrieve lymphocytes and surrounding material in patients with autoimmune encephalitis. The technique was safe and acceptable to this clinical group. The material was distinct from blood and amenable to flow cytometry and cell culture. Here, I aim to validate and further extend analyses from this tool, a key resource for future disease monitoring and experimental applications far more broadly. Participants will undergo paired CLN FNA and blood sampling. To initially explore the effects of age, cognitive impairment, and brain autoimmunity on sample quality, characteristics, and acceptability I will recruit patients ≥65 years with mild cognitive impairment, LGI1-antibody encephalitis, and functional headache with a further group <​45 years (n=5/group). The first objective is sample optimisation for downstream applications. Second, is to determine if neural (phospho-tau, amyloid, and neurofilament light) and immune proteins (cytokine panels) can be detected in the fluid phase using high sensitivity single molecular and multiplex assays, respectively. Third, is to extend cellular phenotyping using spectral flow cytometry. The final aim is qualitative feedback of acceptability and tolerability, focussing on this predominantly older adult cohort ahead of future expansion.

Lay abstract: Brain conditions like dementia are common and disabling. Advances in understanding connections between the brain and immune system could provide new approaches to diagnosis, and identify and monitor responses to new treatments. For example, it is now thought that brain waste and associated immune cells drain from protective layers around the brain into specialised immune centres in the neck. Recently, in patients with autoimmune encephalitis, a brain disease caused by their immune system, we sampled these lymph nodes using ultrasound-guided fine needle aspiration. This safe technique, comparable to a blood test, retrieved distinctive immune cells that we then studied, helping us to understand the disease better. This tool potentially has far broader value in understanding how the brain works normally, like during sleep, and when it goes wrong, like in dementia. In this study, twenty participants will have a blood test and lymph node sample. I aim to improve sample processing to give the best chance of detecting key brain and immune molecules. I will also look for cells that carry brain molecules to the immune system. I will recruit participants with varying age and brain conditions with and without an immune component to explore how sample quality and makeup varies and seek feedback on the experience. This will form a crucial resource for future larger studies. I have chosen to study this because of exciting innovative methods, the science of brain-body communication, and the real world value to patients in improving diagnosis and treatments in complex brain conditions.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL;INFLAMMATORY AND IMMUNE SYSTEM