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July 03, 2024
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Belimumab triggers ‘surge’ of memory B cells in patients with lupus

Fact checked byShenaz Bagha
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Key takeaways:

  • Memory B cells increased at week 2 after belimumab initiation and returned toward baseline by week 52.
  • Insights from the study “might allow for more efficient targeting of the B-cell compartment.”

Belimumab substantially increases circulating memory B-cells in patients with systemic lupus erythematosus, potentially enabling “a more efficient targeting of the B-cell compartment,” according to data published in Rheumatology.

“Data on [belimumab (BEL)’s] effect on [memory B-cell (MBC)] populations are important as circulating autoantibodies persist despite conventional immunosuppressive treatment, even when BEL is employed as an add-on therapy in SLE,” Eline J. Arends, MD, of the Leiden University Medical Center, in the Netherlands, and colleagues wrote. “This persistence can be explained by either the presence of long-lived autoreactive plasma cells resistant to immunosuppression and BEL, or by residual MBCs capable of mounting an autoimmune response.

A rash on the face of a patient with lupus.
Belimumab substantially increases circulating memory B-cells among patients with SLE, according to data. Image: Adobe Stock

“[B-cell activating factor] mediates sites of survival niches for these long-lived cells, and BEL could potentially interfere with this notorious mechanism of therapy resistance, making MBCs susceptible to therapeutic targeting,” they added.

To examine the hypothesis that starting belimumab (Benlysta, GlaxoSmithKline) increases circulating memory B cells in patients with SLE, as well as find “the underpinning mechanism,” Arends and colleagues conducted a meta-analysis of flow cytometric data from a cohort of 1,245 patients. These data were pooled from four randomized, double-blind, placebo-controlled studies of belimumab.

The researchers additionally analyzed the “longitudinal dynamics” of human memory B-cell response following belimumab initiation, using EuroFlow-based high-sensitivity flow cytometry and single-cell RNA sequencing.

By the second week after starting belimumab, patients across “a broad range” of memory B-cell subsets demonstrated a “surge” in circulating memory B cells, according to the researchers. This increase was sustained from weeks 4 through 8, while circulating memory B cells “gradually returned towards baseline levels” by week 52, the researchers wrote. Meanwhile, levels were stable over time in patients treated with placebo.

According to the researchers, patients demonstrated greater increases in memory B cells if they had higher SLE disease activity, were serologically active or were aged younger than 18 years.

In addition, the results of single-cell RNA sequencing suggested that, upon belimumab initiation, memory B cells demonstrated a non-proliferative phenotype with a decrease in activation status and downregulation of many migration genes.

“MBCs can contribute to autoimmune diseases through various mechanisms, including presentation of autoantigens, production of autoantibodies or cytokines, or formation of germinal centers,” Arends and colleagues wrote. “Here, a substantial increase in circulating MBCs, particularly in patients with severe, serologically active SLE/LN, was firmly established upon BEL initiation.

The increase suggests reduced MBC levels in the tissue leading to MBCs no longer interacting effectively with other immune cells, such as T cells, in lymphoid structures, possibly compromising the immune responses,” they added. “The surge of circulating MBCs associated with disrupted lymphocyte trafficking of MBCs, thus, expands the existing understanding of the therapeutic mechanism of BEL’s impact on MBCs in SLE that might allow for more efficient targeting of the B-cell compartment.”