B-cells damage axons during MS
New information in emerging area of MS research could aid therapy
development
Researchers have identified how the body’s own immune system
contributes to the nerve fiber damage caused by multiple sclerosis, a
finding that can potentially aid earlier diagnosis and improved
treatment for this chronic disease.
The study reveals how immune system B-cells damage axons during MS
attacks by inhibiting energy production in these nerve fiber cells,
ultimately causing them to degenerate and die. Study results appear
in the Oct. 15 issue of the Journal of Immunology.
B-cell-axon activity is an emerging area of MS research, one that is
changing how scientists and clinicians can look at this disease. In
this study, Dr. Yufen Qin and fellow researchers from UC Irvine’s
School of Medicine analyzed spinal fluid and tissue samples from MS
patients to identify substances that stimulate a B-cell immune
response. They noted an increased level of B-cell antibodies on
lesions and in spinal fluid bound to two specific enzymes – GAPDH and
TPI.
These two enzymes are essential for efficient energy production. The
researchers believe that the binding of these antibodies to these
enzymes – GAPDH, in particular – may lower the amounts of ATP – the
chemical fuel for cells – available in cells, which eventually can
lead to axon cell degeneration and death. In addition to the energy-
production function, GAPDH is involved with a number of genetic
activities, such as RNA translocation, DNA replication and DNA repair.
Other recent studies have shown that binding of inhibitors to GAPDH
and TPI causes decreased ATP production in neurons, followed by
progressive neuronal degeneration and death. Moreover, patients with
TPI deficiency can develop progressive neurological disorders.
“This research is exciting and potentially important for future
treatments because it identifies new antibodies associated with MS
that can be targeted with emerging therapies,” said Qin, an assistant
professor of neurology. “Significantly, these are the first
antibodies to be identified with axon activity, which is a new area
researchers are exploring in the pathology of MS.”
MS is a chronic central nervous system disease that can cause blurred
vision, poor coordination, slurred speech, numbness, acute fatigue
and, in its most extreme form, blindness and paralysis. Some 400,000
Americans have this disease. Its causes are unknown, and symptoms are
unpredictable and vary greatly in severity.
Much MS research is focused on an autoimmune process in which T-cells
attack and damage myelin, the fatty insulating tissue of axons. These
T-cells do not attack axons themselves; the process of demyelination
interrupts electrical impulses that run through these nerve fibers,
thus causing MS symptoms. Demyelination has been considered the
central feature of MS.
Recently, however, Qin has been among a group of researchers who have
discovered that B-cells too are involved with the autoimmune response
to MS. Instead of targeting myelin, these B-cells attack axons
directly. Axons are the long, slender fibers of a neuron that serve
as the primary transmission lines of the nervous system, and as
bundles they help make up nerves.
Research at UCI and elsewhere has shown that myelin grows back if the
T-cell autoimmune response is turned off, and drugs exist or are in
development to block demyelination. Axons, in turn, repair very
slowly, which implies that B-cell attacks on axons may have a
significant impact on the chronic central nervous system damage
caused by MS.
“Since this area of research is in its early stage, it’s important to
understand the process by which these B-cell responses happen,” Qin
said. “Hopefully, by identifying these two crucial enzymes, it will
lead to a greater understanding of MS and lead to more effective
treatments for people who live with this disease.”
Johanna Kolln, Hui-Min Ren, Reng-Rong Da, Yiping Zhang, Dr. Michael
Olek, Dr. Neal Hermanowicz, Lutz G. Hilgenberg, Martin A. Smith and
Dr. Stanley van den Noort of UCI and Edzard Spillner of the
University of Hamburg also worked on the study. The National Multiple
Sclerosis Society and the National Institutes of Health provided
funding support.
