Scientists zero in on CD29 protein marker as key driver of MS in new study
Protein helps misguided immune cells reach the brain, triggers inflammation
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A close-up look at the adaptive immune system showcases different types of cells. (Photo from iStock)
- In multiple sclerosis, the CD29 protein on immune cells drives inflammation by helping these cells enter the brain, scientists found.
- Tysabri reduces CD29-positive immune cells, suggesting a mechanism for its effectiveness in MS.
- CD29 could serve as a biomarker to predict treatment response and as a target for new MS therapies.
In multiple sclerosis (MS), certain disease-driving immune cells carry a protein marker called CD29, which helps them move into the brain and trigger inflammation.
That is the key finding of a new study by researchers in the Netherlands, who zeroed in on the protein as a driver of MS.
“We identified CD29 as a characteristic and functional marker for [disease-driving immune cells] in MS,” the scientists wrote.
According to the team, the data indicate that this marker may help predict how MS patients will respond to certain disease-modifying treatments.
The study, “Integrin [beta]1 Demarks Precursors of Brain-Residing Antibody-Secreting Cells in Multiple Sclerosis,” was published in the journal Neurology Neuroimmunology and Neuroinflammation.
MS is a chronic neurological disorder in which misguided immune attacks cause damage to the brain and spinal cord. Several immune cell types are involved in this process, including B-cells, which normally produce antibodies to help fight infections.
In MS, some immature B-cells travel from the bloodstream into the brain, where they can mature into inflammatory antibody-secreting cells (ASCs). Although ASCs are thought to be key drivers of MS inflammation in the brain, scientists still don’t fully understand how the precursor B-cells gain access to the brain and develop into these disease-driving cells.
Previous studies have shown that ASCs in the brain and spinal cord often produce high levels of the protein CXCR3, which helps guide immune cell migration. Building on these findings, scientists now analyzed B-cells from people with and without MS to identify additional proteins associated with CXCR3-positive cells.
“Uncovering features of long-lived ASCs in the [brain and spinal cord], and especially their precursors in the circulation, could yield new targets to improve treatment for [people with] MS,” the researchers wrote.
CD29 may help determine treatment response to Mavenclad
The team zeroed in on CD29, also called integrin beta 1, which is another protein that helps control B-cell movement. Through a series of cellular experiments, the scientists showed that B-cells producing both CD29 and CXCR3 had a greater ability to cross from blood into brain tissue, and were more likely to differentiate into ASCs.
“We highlight CD29 as an important marker on CXCR3[-positive] B cells, as coexpression of these markers resulted in enhanced migration capacity and differentiation to ASCs,” the researchers wrote.
The team also examined how these cells change with MS treatments. In blood samples from patients treated with Tysabri (natalizumab), the scientists observed reduced numbers of CXCR3-positive B-cells that were also positive for CD29. Tysabri is an approved MS treatment that works by blocking a molecule on immune cells that pairs with CD29, forming a protein complex involved in cell migration.
“These data demonstrate that treatment of active MS with [Tysabri] effectively reduces CD29 expression on B cells,” the researchers wrote. The team speculated that this effect might be a previously unrecognized mechanism by which Tysabri stops inflammatory immune cells from getting into the brain to drive MS.
In contrast, treatment with Mavenclad (cladribine), another approved MS medication, did not significantly change overall levels of CXCR3-positive B-cells in the blood. Mavenclad works by killing most immune cells, helping a new immune system to form after the short-course therapy.
These data suggest CD29 may help determine response to Mavenclad treatment, though the researchers cautioned that these analyses were limited to a small number of patients, so further work is needed to verify the results.
Overall, the findings suggest that CD29 may help identify circulating B-cells capable of developing into inflammatory ASCs in the brain, offering new insight into the immune mechanisms driving MS and potentially pointing to new ways to monitor or target the disease.
