B-Cell Biomarkers Emerging in SLE, but With Important Caveats

Markers of B-cell activation could prove to be “invaluable” prognostic tools for patients with systemic lupus erythematosus (SLE) and other rheumatic diseases if their efficacy is affirmed in prospective trials, according to new study findings.

Writing in Clinical Biochemistry, corresponding author Mohamed Osman, MD, MSc, of the University of Alberta, and colleagues said B-cell activation is a key component of the pathogenesis of several autoimmune diseases, including SLE.

“Activated B cells can efficiently act as antigen-presenting cells, produce inflammatory cyto- kines, and after differentiating into plasma cells, they are a source of pathogenic autoantibodies,” Osman and colleagues wrote. They added that the success of therapies such as belimumab (Benlysta) and rituximab (Rituxan), both of which target activated B cells, confirms this link.

Recently, the authors said, investigators have turned their attention toward the potential of such biomarkers to track disease progression. Among the biomarkers being investigated are immunoglobulins, free light chains (FLCs), and beta-2 microglobulin (β2M). In their report, Osman and colleagues reviewed the latest research into these and other biomarkers for SLE, Sjögren syndrome, and other diseases.

In the case of SLE, most currently available biomarkers lack the sensitivity or specificity needed to serve as effective tools, the authors said.

“Hence, biomarkers more specifically reflecting B-cell activation may potentially be important in assessing SLE disease progression,” they added.

Immunoglobulins A (IgA), G (IgG), and M (IgM) have been the subject of significant study, with indications suggesting that elevated serum levels of these immunoglobulins could be linked with SLE progression. IgA, specifically, has been associated with kidney disease resulting from SLE. The utility of IgG and IgM, however, is less clear.

“Since IgG has been found to be both high and low in patients with lupus-associated kidney complications, and the utility of IgM in tracking disease progression is inconclusive, clinicians must be cautious when assessing these 2 immunoglobulin indices in SLE patients,” Osman and colleagues wrote.

FLCs have been repeatedly found at higher levels in patients with SLE and disease activity scores, and they have the potential to be useful in monitoring the disease. Specifically, the investigators said κ-FLCs and λ-FLCs could be useful in tracking response to therapy, with the latter perhaps being a meaningful tool to track relapses.

Lastly, β2M concentration has been linked with SLE disease activity and appears to correlate with other inflammatory biomarkers. The literature suggests that elevated β2M could be a sign of more severe SLE, in particular an indicator of lupus nephritis.

In their summary, the authors said all 3 potential biomarker types appeared to be elevated in patients with SLE, but also fluctuated over time, suggesting a potential utility to track treatment response. However, they cautioned that these biomarkers can also be affected by comorbid conditions and nonautoimmune diseases, so clinicians should take a holistic approach to analyzing such results.

Thus, Osman and colleagues said although the evidence suggests immunoglobulins, FLCs, and β2M could become meaningful prognostic tools and treatment-response indicators, the potential for misinterpretation is significant.

“Additional prospective studies utilizing composite disease activity disease indices, these biomarkers, and specific targeted therapies are still needed,” they concluded.

Reference

Du AX, Gniadecki R, Osman M. Biomarkers of B cell activation in autoimmune connective tissue diseases: More than markers of disease activity. Clin Biochem. 2022;100:1-12. doi:10.1016/j.clinbiochem.2021.11.009