June 24, 2020

If you or someone you know has lupus, you probably are aware that the main culprit behind the onset of disease and its symptoms are caused by the accumulation of destructive antibodies. Normally, antibodies recognize foreign invaders, pathogens like bacteria, viruses or parasites, and deem them a threat. This alerts other immune cells to get rid of these pathogens which are coated with antibodies. With lupus, these antibodies, referred to as autoreactive, instead attack healthy tissues and organs.

A recent Lupus Research Alliance-funded study published in the journal, Science Immunology, highlighted a potential therapy that could reduce autoreactive antibodies in lupus patients. Dr. Theresa Lu and her team of investigators led by Dr. Dragos C. Dasoveanu carried out this study to test this potential treatment method.

Antibodies, in general, are made by a type of immune cell called an antibody-forming cell or AFC. These AFCs are present throughout the body to stand guard against specific threats. Dr. Lu’s team looked at AFCs which gather in special regions called lymph nodes. These lymph nodes are where immune responses against foreign invaders are enhanced. This process allows for very efficient immune cells to be created and multiplied. These super-powered immune cells are then released into the bloodstream to reach their specific targets.

What Drs. Lu and Dasoveanu found during research with their mouse models was that a molecule called CCL2 was being released by certain other cells that live in the lymph nodes. CCL2 attracted another group of immune cells called monocytes to this region where AFCs were being made. These monocytes then released molecules of their own called reactive oxygen species (ROS) which limited the number of AFCs, and as a result, reduced the number of antibodies in the bloodstream.

Investigators pointed out that these results shed light on a mode of action that could possibly limit the number of antibody-forming cells and reduce their role in causing autoimmunity. However, they also noted that CCL2 plays an important role in general protective immunity. It can have different functions based on where it is found and which cell is producing it, so blocking the entire immune system may not be ideal. Dr. Lu’s group concluded that while their results show the potential for better treatment of inflammatory diseases and autoimmune diseases like lupus, understanding the source and context of CCL2 will better inform potential targeting in this disease.