Investigating the potential use of highly sensitive tear and saliva analysis to enable non-invasive diagnosis, monitoring, and prognostication in multiple sclerosis

Tanner, Chloe (2024). Investigating the potential use of highly sensitive tear and saliva analysis to enable non-invasive diagnosis, monitoring, and prognostication in multiple sclerosis. University of Birmingham. M.Sc.

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Abstract

Multiple sclerosis (MS) is a progressive neurodegenerative condition characterised by chronic immune-mediated demyelination and axon loss in the central nervous system, leading to progressive decline in motor function and disability. While advancements in treatments have significantly enhanced the longevity and quality of life of individuals living with the condition, timely and accurate diagnosis remains critical. Oligoclonal banding (OCB) and elevated Kappa and Lambda free light chains (FLCs) in cerebral spinal fluid (CSF) are hallmarks of MS. However, CSF sampling via a lumbar puncture is a highly invasive procedure, requires specialist training to perform and is often an unpleasant experience for patients. This study aimed to evaluate the feasibility of non-invasive tear and saliva analysis as alternative methods for the detection of OCB and FLCs.

A cohort of 40 healthy donors (HDs), 20 MS patients and 60 non-MS neurological condition controls (NCCs) undergoing lumbar puncture investigations were recruited to the study. Blood, saliva, tear fluid, and CSF (from lumbar puncture patients) were collected and analysed utilising highly sensitive immunoassays developed by the Clinical Immunology Service. Serum reference ranges for Kappa and Lambda FLCs were established by Optilite analysis, while saliva and tear FLCs were quantified by ELISA. IgG and total free and bound immunoglobulin OCB detection was performed on all sample types using isoelectric focussing (IEF).

Significantly reduced saliva and tear secretion was observed in both MS patients and NCCs compared with HDs. Notably, FLC quantitative parameters exhibited similar trends in MS patients and NCCs when compared to HDs. Kappa FLC secretion and Kappa: Lambda ratios were elevated in serum, decreased in saliva and unchanged in tear fluid when compared to healthy controls. OCB was absent in HDs and NCCs, but faint bands were present in 20% MS patients tears and 25% MS patient saliva.

The tear and saliva biomarkers examined in this study did not achieve sensitivity or specificity requirements to warrant an expansive follow-up study. However, the investigation provided useful insights into the collection and analysis of the sample types. Disparities in results between MS patients may mirror the heterogeneity of MS presentation and disease course, underlining the demand for further biomarker research. The ability to accurately stratify patients based on accurate biomarker profiles could transform clinical investigations for patients and clinicians, pave the way for personalised medicine and increase our understanding of the pathophysiology of the condition. Complementary studies could aim to explore the variability in results among MS patients, particularly regarding the presence of OCBs in tears and saliva. Also, the similarity of FLC parameters between MS patients and NCCs could be investigated through a more stringent cohort analysis of age, medication usage, sample collection times and co-morbidities

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):