LO-043 Single-cell RNA sequencing reveals the dynamics of circulating immune cells in SLE patients treated with belimumab

Background Systemic lupus erythematosus (SLE) has been well known to be associated with B cell hyperactivation with overexpression of B cell-activating factor of the TNF family (BAFF). Belimumab (anti-BAFF therapy) was approved as the first targeted biological drug for SLE. We investigated dynamic feature of immune cells over the Belimumab treatment using longitudinal single-cell transcriptome data.

Methods We conducted single-cell RNA sequencing (scRNA-seq) along with T cell receptor (TCR) and B cell receptor (BCR) repertoire from serial longitudinal PBMC samples (0, 2 weeks, 1, 3, 6 and 12 months after Belimumab) from four Korean patients with SLE.

Results We profiled more than 130,000 PBMC from the four patients at six distinct time points during Belimumab treatment. The mean SELENA-SLEDAI score from the patients decreased from 12.5 at baseline to 3.5 at 12 months. We observed the dynamic changes of several B cell components during Belimumab treatment; decrease of naïve B cells at one month followed by progressive decline in plasmablasts at six months (figure 1). However, although ‘age-associated B’ cell population was clearly identified at the single-cell level in SLE patients, its proportion did not change much over the course of treatment. Intriguingly, there was a notable upregulation of cytotoxic-associated genes (LTB, FCGR3A, KLRC4) in effector memory CD8 T cells (Tem) followed by a significant increase in the frequency of Tem. Peripheral T helper cells (Tph) exhibit higher IFN-G related gene expression compared to other T cell subtypes, which is drastically reduced shortly after Belimumab treatment.

Conclusions We identified dynamic changes of immune cell components along with transcriptomic signatures during Belimumab treatment, suggesting that therapeutic effects of Belimumab occurs through its effect on T cell lineage as well as its effect on B cell lineage.

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