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.
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.
Study Type
OBSERVATIONAL
Enrollment
163
Primary outcome work stream 1
Difference in CD19 count between cohorts
Time frame: Baseline
Primary outcome work stream 2
● CD27 frequency (% of peripheral blood mononuclear cells) at clinical exacerbation of MG compared to when that patient was clinically stable.
Time frame: Relapse within 18 months of recrutiment
Primary outcome work stream 3
● CD27+ frequency (% of peripheral blood mononuclear cells) in MG patients who are symptomatic compared to those who are asymptomatic 12 months following B cell depletion.
Time frame: 12 months after B cell depletion
MG Composite Score
Time frame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups,
MGFA - Post Intervention status
Time frame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
MG QOL-15r
Time frame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
Acetylcholine receptor antibody titre
Time frame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
Lymphocyte Count
Time frame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
Number of relapses requiring hospital admission or rescue therapy
Time frame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
Average daily dose of prednisolone over the three months prior to review
Time frame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
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