The investigators aim to better describe the immune profile in myasthenia gravis (MG), including lymphocyte subset, cytokine and complement profiles; how they differ between patients of different severity, at times of disease exacerbation, and with different immunosuppressive treatments. The investigators hope to build a clearer picture of how different immune measures vary in MG, contributing to the understanding of the patho[physiology of the disease, and working towards a biomarker that might help clinicians optimise an individual's treatment.

the investigators aim to take into account the heterogeneity of MG by taking into account age of onset of MG (early vs late onset) and focussing on acetylcholine receptor antibody (AChR) positive, non-thymomatous MG aged 18-80.](streamdown:incomplete-link)

This study is designed to confirm and refine the knowledge around these changes in the immune profile, including lymphocyte subsets, and complement analysis, between different subgroups of patients with MG of different severity, different levels of immunosuppressive treatment, and at different time points in the disease course, ensuring these are put into the context of the patient's disease subtype (late-onset (LOMG) vs early-onset (EOMG)). This should enable us to understand more about the underlying immune changes in MG, how they relate to disease activity or severity, how this is impacted upon by immunosuppression, and guide us towards a markers for disease severity and effective immunosuppression that could be used in clinical practice, and help guide treatment decisions. One of the challenges in studying patients with MG with the relatively low prevalence of the condition, meaning it can be difficult to recruit large enough numbers of patients; the investigators will work with other tertiary neurology centres throughout England in order to meet recruitment targets.

The research project will consist of three work streams:

1. A one-off observational comparison of the immune profile of patients with different MG severity and in comparison to healthy controls.
2. A prospective observational study examining changes in lymphocyte subset, cytokine and complement profiles associated with clinical exacerbation of myasthenia gravis.
3. A prospective cohort study comparing lymphocyte subset, cytokine and complement profile with disease activity following B cell depletion for refractory myasthenia gravis.

Inclusion Criteria:

• All participants:
• Are able to give valid written consent
• are aged between the ages of 18 and 80

Stable Immunosuppressed

• Have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
• MGFA Post-intervention Status MM or better with no clinical relapse for 2 years
• On either azathioprine or MMF along with ≤5mg/day of prednisolone
• No prednisolone dose increase or decrease in past 12 months
• No increase in azathioprine or MMF dose for 2 years (allowing for cessation for up to 1 month)

Stable Non-Immunosuppressed

• have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
• MGFA Post-intervention Status MM or better on only low-dose cholinesterase inhibitors (≤<120 mg pyridostigmine/day) for over two years and ≤5mg/day of prednisolone for over two years.
• No prednisolone dose increase or decrease in past 12 months

Refractory

• have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
• have been deemed eligible to be refractory to standard treatment and eligible for rituximab as per the NHS England criteria.

Exclusion Criteria for all participants:

• Are unable to give valid consent
• Co-existing autoimmune condition for which azathioprine or mycophenolate mofetil are treatments (e.g. inflammatory bowel disease, rheumatoid arthritis, neuromyotonia)
• Currently undergoing treatment for solid organ or haematological malignancy, or previous thymoma
• Clinical frailty scale ≥6

Acetylcholine receptor antibody positive myasthenia gravis