There has been a significant increase in our understanding of how the COVID-19 pandemic has affected SLE patients, according to a new review article on the subject.
B cell abnormalities in SLE patients have been found in a wide range of studies, making it difficult to fully understand how these abnormalities affect the disease. Some of the most recent findings and implications are discussed in this new article. Current Opinion in Rheumatology published the review.
Flow cytometry and mass cytometry have helped to identify two key B-cell subsets that appear to be prominent in SLE, according to the authors.
Recent research in SLE found that antigen-experienced B cell subsets lacking CD27 and IgD defined by their lack of CXCR5 and CD19low expression are expanded in SLE and represent plasmablasts that are likely escaping proper selection,” the researchers reported.
The study of antibody-secreting cells (ASCs) has yielded promising new treatment targets, according to the authors. Investigators believe that the checkpoint molecule BTLA, which they say inhibits plasmablast induction in healthy patients, is among them.
Naive B cells from SLE patients had lower levels of BTLA expression and did not play an inhibitory role in the study, the authors write. “This could explain why ASCs are expanding or not being properly selected,” they conclude.
FOXM1 has been found to be expressed at a higher rate in CD38+ B cells compared to naive or memory B cells, particularly in plasmablast from SLE patients. An important therapeutic target could be found in this way. IL-17RA/RC, sFas ligand, and CD52 are also possible targets.
Scientists are also looking beyond biologics and small molecules, according to the researchers. Chimeric antigen receptor (CAR) T cells are being studied as a potential treatment option.
Anti-CD19 CAR T cells were shown in a study in mouse models to help deplete B cells and reduce autoantibodies as promising research.
According to the study’s authors, treatment with CD19 CAR T cells in an otherwise refractory SLE patient “led to rapid serological and clinical remission.”
According to them, “Further promising approaches to modulate the B cell compartment are currently under investigation,” such as CAR T cells that are bi-specific against CD19 and CD22, or BCMA and CD38.
They also examined how the COVID-19 pandemic influenced the scientific community’s view of immunosuppressive therapy. SLE patients do not appear to be at an increased risk of contracting SARS-CoV-2, according to the available data, but they do present more severe symptoms if they do become infected.
COVID-19 infection may cause SLE flare-ups or new onset, but this is still up for debate, they wrote. It’s also been reported that COVID-19 patients without prior autoimmune disease have elevated levels of anti-SSA/Ro antibodies and increased antiphospholipid antibodies.
The vaccine appears to be effective in this patient population, according to the authors, without increasing the risk of flare-ups, they added. Although some research suggests certain SLE therapies may affect vaccine response, they did add that.
SLE patients with low baseline IgG levels prior to vaccination were found to have an impaired humoral response to the BNT162b2 mRNA vaccine, as were those who had been treated with mycophenolate mofetil (MMF) and methotrexate. Patients taking rituximab (Rituxan) had a lower response to vaccination and a reduced humoral immune response during acute infection, according to another study.
It’s possible that public health officials may need to rethink their vaccination protocols for these patients, according to the researchers.
