A clinical and immunological study on late onset Myasthenia Gravis

Sadalage, Girija (2021) A clinical and immunological study on late onset Myasthenia Gravis. PhD thesis, University of Nottingham.

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Abstract

Myasthenia gravis is an autoimmune disorder of neuromuscular transmission caused by antibodies to the acetylcholine receptor and related components on the post synaptic membrane of the neuromuscular junction. Recent evidence has shown that the incidence of late-onset myasthenia gravis, defined as onset at more than 50 years of age, has been increasing. We sought to prospectively recruit patients newly diagnosed with myasthenia gravis and look at their clinical and immunological profile to see if there are any differences between early onset and late-onset myasthenia gravis.

Methods: This was a multicentre study across Nottingham, Birmingham and Oxford. We recruited 150 patients with myasthenia gravis across the three sites, newly diagnosed within the preceding 12 months. We did clinical examinations, completed MG composite scores (MGC), MG Quality of life scores (MG QOL), and blood tests including serum for antibodies, and whole blood for PBMC isolation and T-cell studies. These were repeated at annual follow up. The antibody studies were performed at Oxford by radioimmunoassay (RIA) and cell based assays (CBA) for acetylcholine receptor antibodies (AChR), muscle specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies.

Results: We recruited 150 patients with myasthenia gravis, 76% of whom had LOMG, with a female to male ratio of 1:1.6. EOMG patients more frequently had ocular myasthenia compared to LOMG patients, 94.7% of patients were seropositive for either AChR, MuSK or LRP4 antibodies. T-cell studies showed that the pro-inflammatory and anti-inflammatory cytokine balance is disrupted in all MG patients with decreased Treg percentages and increased production of IL10, IL17 and TNF alpha, which is more pronounced in patients with AChR antibodies. The clinical presentation did not show any difference between the different antibody subgroups, but there was a milder, more indolent course in seronegative patients, and AChR + MuSK double positive patients were more likely to need steroids on generalisation. The majority of the patients responded well to treatment with improvement in MGC, MG QOL and AChR RIA titres with time.

Conclusions: To our knowledge, this is the largest prospective study on the clinical and immunological aspects of late-onset myasthenia gravis to date. Further studies on B cells in MG along with micro-RNAs as biomarkers in MG are being done.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Maddison, Paul
Constantinescu, Cris
Keywords: Myasthenia Gravis, Ocular myasthenia, Late onset myasthenia, Acetylcholine receptor antibodies, MuSK antibodies, LRP4 antibodies, Treg cells
Subjects: W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Health Sciences
Item ID: 65267
Depositing User: Sadalage, Girija
Date Deposited: 04 Aug 2021 04:41
Last Modified: 04 Aug 2021 04:41
URI: http://eprints.nottingham.ac.uk/id/eprint/65267

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