Developing antigen specific immunotherapy for myasthenia gravis
Research type
Research Study
Full title
Identification of antigen processing independent epitopes for developing antigen specific immunotherapy in myasthenia gravis
IRAS ID
305139
Contact name
Saiju Jacob
Contact email
Sponsor organisation
University of Birmingham
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Myasthenia gravis (MG) is a T-cell dependant B-cell mediated autoimmune disease which targets nerve and muscle junction, resulting in weakness of eye muscles. It progresses to cause generalised muscle weakness in limbs or more worryingly, bulbar muscles (leading to swallowing, speech or breathing difficulties). With incidence of 0.3 to 2.8 per 100,000 per year, it is not an uncommon disease.
In 85% of patients with generalised MG, the specific and the commonest antigenic target is acetylcholine receptor (AChR).
Current treatment for MG targets various aspects of T and B cells in a generic fashion. Even though many of these treatments are effective to some extent, they come with significant side effects due to reduced immunity and also complications from chemotherapeutic agents. There is an urgent need to target specific immunotherapy.
Antigen specific immune tolerance have been tested on animals or in vitro human immune cells with use of AChR or its peptides but with limited responsiveness likely due to dissemblance to naturally processed epitopes or even worsening of MG from further stimulation of AChR specific CD4+Tcells.
Our project aims to identify antigen processing independent epitopes that can effectively induce tolerance of immune system to AChR. Our work will involve testing of immune cells of patients and healthy volunteers in vitro and HLA DR3 transgenic mice with preliminary AChR peptides to come up with ‘Designer peptides’.
We will collect blood sample from patients and healthy volunteers with a written consent and we will also obtain peripheral blood from NHS Blood and Transplant.
This project will last for 3 years and is funded by Myaware charity. Laboratory research will be carried out at Institute of Immunology and Immunotherapy, University of Birmingham. We will recruit patients from 15 NHS England Trusts and 1 NHS Scotland Trust.REC name
West Midlands - Black Country Research Ethics Committee
REC reference
22/WM/0030
Date of REC Opinion
11 Feb 2022
REC opinion
Further Information Favourable Opinion