B-cells Differ in Pediatric- and Adult-onset MS, Study Shows

The immune system B-cells responsible for producing antibodies are different in those who develop multiple sclerosis (MS) as children, than in those who develop it as adults, a study shows.

The research, “B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis,” was published in the journal Neurology: Neuroimmunology & NeuroInflammation.

Because only 3 to 4 percent of patients develop MS before they’re 18, the major expansion in treatment options over the past few decades has focused on adults. But attention also needs to be focused on developing therapies for youth, researchers said.

MS is an inflammatory disease of the central nervous system. Differences between the immune systems of children and adults lead to different disease patterns in the two.

Those under 18 have more inflammation, more frequent relapses, and an increased risk of irreversible disability early in the disease.

As a result, “it is important to identify immunologic similarities and differences between pedMS [pediatric-onset MS] and adult-onset multiple sclerosis (adMS) so as to better appraise treatment effects when novel drugs are applied in patients with pedMS,” the researchers wrote.

They compared B-cells in the blood and cerebrospinal fluid (CSF) of pediatric-onset and adult-onset MS patients. CSF is the fluid that surrounds the brain and spinal cord.

The team analyzed blood and CSF samples from 25 patients with pediatric-onset MS, ranging from 8 to 18 years old; 40 patients with adult-onset MS, ranging from 23 to 65 years old; and blood specimens from 66 controls, ranging from 1 to 55 years old.

They used a technique called flow cytometry to analyze B-cells’ presence and composition.

The team discovered significant change in the B-cells of healthy controls as they aged. They noted a significant decrease, in particular in naive B-cells, which constitute 90 percent of the B-cells in the blood of newborns. Naive B-cells have yet to be exposed to an antigen, a foreign substance that triggers an immune response in the body.

The finding agreed with previous studies showing that a decline in naive B-cells is accompanied by an increase in B-cells with antigen-experienced memory. The immune system can remember a previous pathogen attack or injury and generate an enhanced response that depends on the memory-cell populations.

Researchers discovered that the age-dependent naive-to-memory B-cell ratio is almost lost in patients between 12 and 55, however.

They also noticed changes in B-cell patterns in CSF when they compared pediatric-onset and adult-onset MS patients who had experienced an acute relapse. This suggested that some B-cell changes in MS patients occur independent of age.

But the team did notice B-cell changes in pediatric-onset patients that they didn’t find in adult-onset patients. They found more unswitched memory B-cells and ordinary plasma B-cells in pediatric-onset patients, and more class-switched memory B cells and terminally differentiated plasma B cells in adult-onset patients.

B-cells produce several classes of antibodies, also referred to as immunoglobulins (Ig). Class switching involves B-cells producing different kinds of antibodies. Naive mature B-cells produce the classes IgM and IgD. After activation and through interaction with specific signaling molecules, they begin producing IgG, IgA or IgE antibodies. Each of the classes has different effector properties.

Overall, the team concluded that there are specific alterations in “B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults,” and emphasized that the results “support the role of B cells and humoral immunity as an important component of MS pathology in young patients with early-stage MS.”