Predicting by means of in vitro tests the treatment response in patients with MG

Myasthenia gravis (MG) with the presence of antibodies against the
acetylcholine receptor (AChR) is a well-characterized neurological autoimmune
disease. Overall, treatment strategy is established, however, treatment
responses vary widely between patients. While some improve rapidly, many
require long-lasting treatment with several immunosuppressive drugs to achieve
(partial) remission, and many MG patients will remain treatment refractory.
Muscle weakness, treatment side effects and treatment efficacy variability all
contribute to a reduced quality of life, especially in severe and
treatment-refractory MG patients.
Currently, there is no method available to predict the effect of
immunosuppressive drugs in individual patients.
Therefore, isolation of lymphocytes and plasma cells, including long-lived
plasma cells (LLPCs), that are present in the thymus, blood and bone marrow
could be helpful to study the efficacy of different therapies targeting these
specific cell types. This could provide an overview of lymphocyte population
and potential resistance by assessing in vitro response to various
immunosuppressive drugs.

The first aim of this study is to use an in vitro approach using patient*s
derived material to accurately and rapidly predict the optimal therapeutic
approach that will predict a good clinical response in individual patients. The
second aim of this study is to establish a new imaging modality that can
accurately identify TLH from normal thymic tissue to prevent unnecessary
surgery.

This is an observational study with no pharmacological intervention performed
in the Maastricht University Medical Centre+ (MUMC+). Combining imaging,
pathology and molecular biology, patient material will be analyzed and the in
vitro results correlated to clinical outcome of the patient.
Fresh thymus, BM and blood will be collected from patients undergoing
thymectomy, processed and subsequently cultured for the purpose of testing
immunosuppressive and novel therapeutics in vitro. 20 AChR-MG patients will
undergo 3-T imaging to observe presence or absence of TLH. The in vitro and
imaging results of these patients will be correlated with the clinical
information available on disease severity and treatment response before and
after thymectomy, during follow-up visits at the MUMC+ and/or other medical
centers. The 3-T imaging is only additional and will not interfere with any
surgery/treatment decisions.

Blood withdrawl: 80 mL blood is taken during outpatient clinic and then at 3
further follow-up time points. It involves minimal risk and discomfort.
Thymectomy: robotic assisted thorascopic thymectomy is part of standard
treatment in AChR-MG patients and it is considered low-risk. In non-MG thymoma
patients, resection is usually performed as a regular treatment as well. Rest
material retrieved post-thymectomy does not change the burden on patients.
Bone marrow biopsy: 10-20 mL of BM aspirate will be obtained under general
anesthesia from the posterior superior iliac crest. Additionally a bone marrow
biopsy cylinder will be removed from the solid bone marrow in the same bone. BM
aspirate and biopsies are considered low risk. Patients will not experience
discomfort during the procedure as they will be under anaesthesia, however,
some pain can be experienced post-biopsy. Main risks include: fever, infection
and/or prolonged bleeding at biopsy site.
Patients will be asked if they agree that their material will be stored in the
biobank for the purposes described in this study and/or other related studies.
Patients will be informed that their stored samples will be disposed of, upon
the patient*s request, and according to laws and regulations.
The results could provide the basis to predict an efficient therapeutic
strategy for every individual patient, resulting in personalized
immunosuppressive treatment strategies.
The patients will not directly benefit from participating in this study but the
research could help to understand the disease mechanisms and whether the
therapeutic response observed in vitro mimics the clinical improvement of the
patient. In the future this approach can be used as a predictive assay for
therapeutic efficacy of different compounds.