New Research Elucidates Role of B Cells in SLE

New subsets of patients with systemic lupus erythematosus (SLE) and new therapeutic targets have been discovered in recent years.

Recent research into B-cell abnormalities in systemic lupus erythematosus (SLE) has led to a number of potential therapeutic targets and yielded a better understanding of how patients have been affected by the COVID-19 pandemic, according to a new review article.

Many studies have identified abnormalities of B cells in patients with SLE, but those abnormalities have varied widely, making it difficult to fully understand the roles such abnormalities play. In the new article, investigators explained some of the recent findings and where they leave the field. The review was published in the journal Current Opinion in Rheumatology.

The authors said that better technology, including multicolor flow cytometry and mass cytometry, has helped to identify 2 key B-cell subsets that appear to be prominent in SLE.

“A recent study in SLE found that antigen-experienced B cell subsets lacking expression of CD27 and IgD defined by their lack of CXCR5 and CD19low expression are expanded in SLE and represent plasmablasts likely escaping proper selection,” the investigators reported.

The authors said research looking at the role of antibody secreting cells (ASCs) has led to potentially fruitful new treatment targets. Among them are the checkpoint molecule BTLA, which the investigators said is believed to inhibit plasmablast induction in healthy patients.

“In a recent study, naive B cells of SLE patients showed reduced BTLA expression and lack this inhibitory role, which could explain expansion of or lack of appropriate selection of ASCs,” the authors said.

They also wrote that the transcription factor FOXM1 has been found to be expressed at higher rates in CD38+ and CD43+ B cells compared with naive or memory B cells, particularly in plasmablast from patients with SLE. This could render it a useful therapeutic target. Other potential targets include IL-17RA/RC, sFas ligand, and CD52.

However, the investigators said scientists are also looking beyond biologics and small molecule therapies. One area of research is chimeric antigen receptor (CAR) T cells.

Promising research includes a study in mouse models that showed anti-CD19 CAR T cells can help deplete B cells and reduce autoantibodies.

A study of CD19 CAR T cells in a patient with otherwise refractory SLE “led to rapid serological and clinical remission including signatures of lupus nephritis,” the authors reported.

“Further promising approaches to modulate the B cell compartment, anti-CD19 and anti-CD38, bi-specific anti-CD19/CD22 or BCMA/CD38 CAR T cells are currently under investigation,” they said.

Finally, the authors looked at how the COVID-19 pandemic informed the scientific community’s understanding of immunosuppressive therapy. They said existing data suggest that people with SLE do not have a higher risk of SARS-CoV-2 infection, but they tend to have more severe cases when they are infected.

“Whether COVID-19 infection might trigger flares or new onset of SLE remains a matter of debate,” they wrote. “Nevertheless, elevated levels of anti-SSA/Ro antibodies and increased antiphospholipid antibodies and other specificities have been reported in COVID-19 patients without prior autoimmune disease.”

The authors noted that vaccination appears to be effective in this patient group, without increasing the risk of flares. However, they added that some research suggests that certain SLE therapies might affect vaccine response.

“A study just focusing on mRNA vaccine BNT162b2 screened 126 SLE patients and found impaired humoral response in patients with reduced naive B cells and low baseline IgG levels prior to vaccination and patients treated with mycophenolate mofetil (MMF) and methotrexate,” they wrote. Meanwhile, another study found that patients taking rituximab (Rituxan) had a reduced humoral immune response in acute infection and a lower vaccination response.

The authors said these findings suggest that public health officials may need to reconsider immunization protocols in these patients.

Reference

Szelinski F, Lino AC, Dörner T. B cells in systemic lupus erythematosus. Curr Opin Rheumatol. 2022;34(2):125-132. doi:10.1097/BOR.0000000000000865