Objective: To characterise T- and B-lymphocyte senescence in early stage Parkinson’s disease (PD).

Background: Evidence suggests that the immune system may contribute to PD aetiopathogenesis, and this represents a tractable target for disease-modifying therapy. Given that ageing is a risk factor for PD, we sought to characterise age-related immune changes (immunosenescence) in PD. Recent work has shown that PD patients have a more activated and less senescent T-cell profile than age-matched controls [1]. In a new patient cohort, we aimed to replicate findings with respect to T-cell senescence, and, for the first time, characterise B-cell senescence in PD.

Method: Blood samples were collected from 20 patients with early PD (mean disease duration 0.8 (0.5) years) and 20 controls. T- and B-cell senescence subsets were identified using flow cytometric immunophenotyping. CMV and EBV serostatus was ascertained, given the well-documented effect of viral infection on immunosenescence.

Results: CD4+ ‘TEMRA’ cells, markers of T-cell senescence, were numerically reduced in PD cases versus controls (p=0.046). This was not driven by differences in age or CMV/EBV serostatus across groups. CMV positivity was associated with a rise in CD4+ TEMRA cells as expected in controls, but not in PD cases. In addition, switched memory B-cell counts were lower in patients versus controls (p=0.040). No changes were observed in the CD8+ T-cell pool.

Conclusion: These findings suggest that the senescent ‘shift’ induced by viral infection and ageing is abnormal in early PD. The functional relevance of this has yet to be elucidated, but a reduction in ‘long-lived’ lymphocyte pools may favour the passage of more activated, clonally less restricted lymphocytes across the blood brain barrier, promoting central inflammation and dopaminergic cell loss. Pragmatically, this study shows that peripheral immune abnormalities may be present even in early stage disease, adding urgency to the search for immune-modulating therapies in PD. Presented at the British Society for Immunology Conference (27/9/18).

References: (1) Williams-Gray CH, Wijeyekoon RS, Scott KM, Hayat S, Barker RA, Jones JL. Abnormalities of age-related T cell senescence in Parkinson’s Disease. Journal of Neuroinflammation. 2018;15(1):166.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lymphocyte-senescence-in-parkinsons-disease/