Research Highlights

New risk gene that triggers multiple sclerosis 

Published online 16 June 2015

New research identifies a pivotal gene in multiple sclerosis, linking it to the most important genetic factor that drives the disease. 

Biplab Das

When they escape to the brain, defective immune cells can cause multiple sclerosis
When they escape to the brain, defective immune cells can cause multiple sclerosis
© Cultura RM / Alamy
The human leukocyte antigen class II proteins (HLA-II) is the strongest genetic factor that influences multiple sclerosis. It helps the immune system distinguish the body’s own proteins from foreign proteins, and disturbing this system increases the chances of auto-immune disease. Researchers from The Netherlands and Qatar have discovered how mutation of a single base in the CLEC16A gene interferes with the normal function of HLA-II. 

The mutation in CLEC16A results in a faulty HLA-II system, generating blind immune cells that are unable to differentiate pathogen-derived proteins (also known as antigens) from the body’s own proteins. When such blind immune cells escape to the brain, they destroy nerve-insulating myelin, resulting in multiple sclerosis. 

The scientists found that silencing the activity of the CLEC16A gene in specific antigen-presenting cells disrupted the ability of HLA-II to display antigens on the cell membrane. Next, they identified that the levels of inactive CLEC16A protein in peripheral blood mononuclear cells of multiple sclerosis patients were two times higher than those of healthy individuals, indicating that CLEC16A has a role in the disease.  

“In the future, immunology will continue to unravel what all the risk genes such as CLEC16A really do in the complex adaptive immune system, hopefully aiding the development of new drugs that could interfere with relevant disease-causing pathways,” says lead author Rogier Hintzen from the University Medical Centre, Rotterdam. 


  1. Lujin, M. M. et al. Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis. Brain (2015).