Immune B-cell Subsets Correlate with MS Progression, Study Finds

Australian scientists have discovered subsets of immune cells that differ between people who have multiple sclerosis (MS) and those who don’t. Because the prevalence of these cells correlates with autoimmune attacks, they represent potential targets for MS therapies.

The study, “IgG3 + B cells are associated with the development of multiple sclerosis,” was published in the journal Clinical and Translational Immunology.

Therapies that target a class of immune cells called B-cells have shown promise in halting both relapsing-remitting multiple sclerosis (RRMS) and more progressive forms of the disease.

Using a cutting-edge technology called mass cytometry, which can measure features of single cells, researchers at The University of Sydney discovered nine different subsets of B-cells, according to a press release from MS Research Australia, which supported the study.

Each subset was identified by its unique composition of cell surface proteins — like CD21, CD24, CD27, and CD38 — and all produce a type of antibody called IgG3.

When serum (blood) levels of IgG3 rose, so did the prevalence of these B-cell subsets.

High levels of IgG3 have long been associated with autoimmunity, particularly in MS. The team discovered a strong association between two particular subsets of IgG-positive B-cells — called CD21+CD24+CD27-CD38- and CD27+CD38-CD71- memory B‐cells — and the conversion between clinically isolated syndrome (CIS), which is a single occurrence (often the first) of neurological symptoms, and full MS.

Serum IgG3 levels and those of the IgG3-producing B-cells rose in CIS patients close to converting to MS.

“These data suggest that there may be an inherent defect in the IgG3 B-cell compartment that is affected by the course of MS disease,” the researchers wrote.

One of these subsets — the CD21+CD24+CD27-CD38- B-cells — was subsequently observed in high levels in a separate, independent group of patients. Interestingly, that B-cell subset increased significantly during active versus inactive MS.

Another subset, the CD21+CD24+CD27+CD38- subset, also was present in high levels in patients with active MS.

Narrow-band UV radiation therapy, also called phototherapy, appeared to reduce the amount of circulating IgG3-bearing B-cells. In a phototherapy clinical trial called PhoCIS, 100% of CIS patients who did not receive phototherapy developed MS within 12 months, compared to only 70% of those who received phototherapy three times per week for eight weeks.

Notably, certain subsets of the IgG3-producing B-cells responded more to phototherapy — including the CD21+CD24+CD27+CD38- subset — compared to others, indicating that such therapy may work better for some patients.

Although it remains unclear exactly how IgG3 affects MS progression, the study suggests that IgG3-producing B-cells may serve as biomarkers for the progression of MS and that targeting them therapeutically can protect CIS patients from transitioning into MS.

“In conclusion, mass cytometry has provided us with unprecedented insight into the changes that occur in IgG3 B-cells as CIS patients convert to MS, and when MS patients develop active forms of the disease. Our results highlight that interventions (e.g. phototherapy) that reduce these populations of IgG3 B-cells protect CIS patients from transitioning to MS,” the researchers wrote.

“These findings justify consideration for subsets of IgG3 B-cells as biomarkers and/or mediators of disease progression in MS, as well as future targets of novel immunotherapies,” the team concluded.