MS May Develop in Lymph Nodes, Not Autoimmune System

Multiple sclerosis (MS) may initially develop in the lymph nodes, and not the autoimmune system as previously thought, according to researchers at Yale University.

The study, published in Science Translational Medicine, aimed to understand the origin of MS, as well as the disease’s contribution to tissue damage, which leads to numbness, loss of vision, and debilitating fatigue in patients.

“The brain of an MS patient contains a type of immune cell — called a B cell — that current research believes may be ​one of the cells responsible for attacking brain tissue, but we have been unable to ​determine where ​in the body these cells are taught to attack brain tissue,” Joel N. H. Stern, PhD, a contributor to the study, said in a statement. “Our objective was to determine the origin and map the course of these cell abnormalities in the hope of targeting them for further investigations in MS treatment.”

The researchers noted the central nervous systems (CNSs) of MS patients have expanded clones of antigen-experienced B cells, which can influence the meninges, cerebrospinal fluid (CSF), and parenchyma. The investigators believe the B cells in the CSF can interact with the peripheral blood, which would allow it access to lymphoid tissue. Cervical lymph nodes (CLNs) were observed after coming in contact with mature CNS cells. The data showed expanded B cells were present in both compartments, shown by antibody sequencing.

“This helps explain why treatments that work outside the central nervous system can ease MS symptoms and may give us clues how to develop even more effective treatments,” Kevin O’Connor, one of the paper’s senior authors, said in a statement.

Founding members of clone communities were found more frequently in the draining CLNs compared with the non-draining CLNs, including lesions.

The researchers believe this new information proves B cells travel freely across tissue barriers, including throughout the cerebrospinal fluid. They also believe the B cells mature outside the CNS in the secondary lymphoid tissue.

“Our study may aid in further defining the mechanisms of immunomodulatory therapies that either deplete circulating B cells or affect the intrathecal B cell compartment by inhibiting lymphocyte transmigration into the CNS,” the authors concluded.

A simultaneous investigation focused also on the CNS, on the movement of blood and the spinal cord.

“Together, these two studies allow us to understand the movement of these disease-causing B cells in greater detail than ever before,” Stern described the synthesized findings. “It is an approach that can non-invasively evaluate different treatments and their effect on autoimmunity in people with MS.”