Objective: To characterise the profile of innate immune cells in the nasal cavity in people with Parkinson’s disease (PD) versus controls.

Background: Neuroinflammation provides novel avenues for development of new therapeutic strategies for PD, with both peripheral and central inflammation implicated in disease onset and progression (1). Multiple studies have reported changes in the adaptive immune system, but innate immune changes are less well characterised. Furthermore, most studies have focused on blood, but the nasal cavity represents an early site of alpha-synuclein pathology and may be highly relevant for characterising early immune changes (2).

Method: Matched nasal swabs (x 4) and blood samples were collected from 25 people with early-stage PD, 10 people with late-stage PD and 15 healthy age and sex-matched controls without immune/inflammatory comorbidities or medications. Nasal immune cells were isolated through filtration and centrifugation and PBMCs were extracted using standard techniques. Cell samples were immunophenotyped using spectral flow cytometry with a panel of eighteen markers to characterise changes in the proportion and activation state of NK cells, monocytes and neutrophils.

Results: Immune cell numbers isolated from nasal swabs were sufficient to identify neutrophil, monocyte and NK cell subsets. CD45⁺ immune cells in the nose in PD were significantly more abundant in PD versus controls, and this correlated with more severe hyposmia (Odofin^TM Sniffin’ Sticks score). Nasal total neutrophils and mature neutrophils (as proportions of CD45⁺ cells) were higher in PD versus controls, along with a significant increase in neutrophil-to-lymphocyte ratio (NLR). These changes were specific to nasal samples and not mirrored in the blood. Further data analysis is ongoing.

Conclusion: Nasal swabs represent easily accessible biosamples from an area highly relevant to PD pathology. Characterisation of innate immune changes within these samples is feasible and our pilot data indicates elevated nasal neutrophils in PD. This warrants further exploration for biomarker discovery in PD.

References: 1. Roodveldt C, Bernardino L, Oztop-Cakmak O, Dragic M, Fladmark KE, Ertan S, Aktas B, Pita C, Ciglar L, Garraux G, Williams-Gray C, Pacheco R, Romero-Ramos M. The immune system in Parkinson’s disease: what we know so far. Brain 2024;147(10):3306-24.

2. Stefani A, Iranzo A, Holzknecht E, Perra D, Bongianni M, Gaig C, Heim B, Serradell M, Sacchetto L, Garrido A, Capaldi S, Sánchez-Gómez A, Cecchini MP, Mariotto S, Ferrari S, Fiorini M, Schmutzhard J, Cocchiara P, Vilaseca I, Brozzetti L, Monaco S, Jose Marti M, Seppi K, Tolosa E, Santamaria J, Högl B, Poewe W, Zanusso G. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain 2021;144(4):1118-26.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/characterising-immune-changes-in-the-nose-in-parkinsons-disease/