Investigating antibody-driven inflammation in MS

Dr Stephanie Trend

Telethon Kids Institute, WA

January 2020

specialisation: Immunology

focus area: Better treatments

funding type: Project

project type: ebv

Summary

MS is a condition where a person’s immune system mistakenly attacks the fatty, protective layer, called myelin, around nerves in the brain and spinal cord. The resulting damage can cause a range of symptoms and disability. 

Why the immune system mistakenly attacks the body is unknown. Dr Trend and her team investigated whether there are any intrinsic differences between immune cell functions in people with MS compared to people without MS. She did this by examining immune cells from the blood of people with MS and those without MS.  

The team examined whether cells from people with MS are primed to give a more inflammatory response when exposed to antibodies (small proteins produced by the immune system that bind foreign substances that invade the body and activate the immune system) compared to those who do not have MS.  

The team also investigated whether people at an early MS stage have the same responses to antibodies as those with more advanced disease. 

Progress

Dr Trend has made great progress with this project, resulting in the publication of her results in a prestigious scientific journal, Frontiers in Immunology. Her research demonstrates that women with MS exhibit unique alterations in a specific type of immune cell known as B cells. B cells are responsible for producing antibodies to fight infection. As a built-in feedback loop, some B cells have a sensor molecule that detects when antibodies have been produced and dampens down the B cell immune response so that it does not become excessive. However, Dr Trend has shown that the levels of this sensor molecule are reduced in B cells of women with MS. This could impair their ability to switch off autoimmune responses and influence their capacity to fight infections such as Epstein Barr Virus (EBV), which is associated with an increased risk of MS. More information about these findings is here. 

Dr Trend next examined some of the downstream pathways when the sensor molecule on the B cell is triggered by antibodies. To accomplish this, she established and optimised cutting-edge techniques, developed analysis pipelines and established collaborations. 

Dr Trend’s research indicates that B cells are likely to activate T cells, another type of immune cell, in people living with MS. This is important as both B and T cells are implicated in the development of MS. 

Moving forward, Dr Trend plans to conclude the analysis of this data and prepare a manuscript for publication in a peer-reviewed scientific journal. 

Outcome

In this project, Dr Trend and her team found that in people with MS, various subsets of B cells (a type of immune cell) are activated based on their expression of proteins on the cell surface. Early analyses show that these B cells may be more likely to activate T cells (another type of immune cell) in people with MS than in people without MS. It appears that some B cells are likely to be better at activating other immune cells or travelling to the brain to contribute to MS. Dr Trend and her team are now trying to find out what has activated these particular types of B cells. 

Dr Trend and her team are now preparing a scientific manuscript for publication in a peer-reviewed journal. 

publications

Trend S, Leffler J, Teige I, Frendéus B, Kermode AG, French MA, Hart PH. FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis. Front Immunol. 2021 Jan 11;11:614492. doi: 10.3389/fimmu.2020.614492. PMID: 33505402; PMCID: PMC7832177. 

Updated: 31 March 2024

lead investigator

total funding

$170,470

start year

2020

duration

4 years

STATUS

Past project

Stages of the research process

Fundamental laboratory Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline

10+ years

Translational Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline

5+ years

Clinical Studies and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline

3+ years

Read More

Newsletter subscription

  • Enter your details

Investigating antibody-driven inflammation in MS