# Unveiling biomarkers of telitacicept’s efficacy in SLE treatment through proteomics and metabolomics

**Authors:** Huiyu Nie, Siyuan Chang, Hanhan Chen, Jiahui Shi, Shu Li, Xiaofei Peng, Wei Cheng, Jia Wang, Qi Tang, Yan Ge, Xi Xie, Fen Li

PMC · DOI: 10.3389/fimmu.2026.1779880 · Frontiers in Immunology · 2026-03-04

## TL;DR

This study identifies biomarkers linked to how well Telitacicept treats lupus, using proteomics and metabolomics to better understand treatment responses.

## Contribution

The study introduces novel protein and metabolite biomarkers associated with Telitacicept's efficacy in SLE patients.

## Key findings

- XPNPEP3, SRSF5, SRSF6, WARS1, IDH1, and ITLN1 are protein biomarkers correlated with Telitacicept efficacy in SLE patients.
- Pyruvate is a potential metabolic biomarker for responders, while GABA is a potential biomarker for non-responders.
- Pyruvate and IDH1 are involved in the citric acid cycle, and GABA negatively correlates with XPNPEP3.

## Abstract

The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with abnormal activation of B lymphocytes. Telitacicept simultaneously blocks B-cell stimulating factors and proliferation-inducing ligands, thereby inhibiting B-cell proliferation and differentiation, demonstrating favorable therapeutic efficacy in the majority of SLE patients. However, there is a lack of reliable biomarkers of efficacy and systematic elucidation of its mechanism of action.

The study employed proteomics and metabolomics analysis to explore biomarkers and mechanisms underlying therapeutic response variability to Telitacicept in SLE patients. Twenty-five SLE patients were enrolled and divided into the responder group and non-responder group based on the SLE Response Index 4 to identify key proteins, metabolites, and mechanisms associated with treatment response.

Proteomics results revealed XPNPEP3, SRSF5, SRSF6, WARS1, IDH1, and ITLN1 as protein biomarkers correlated with Telitacicept efficacy in SLE patients. Metabolomics results indicated that pyruvate was a potential metabolic biomarker for responder group, while gamma-aminobutyric acid (GABA) was a potential biomarker for non-responder group. The combined analysis revealed that both pyruvate and IDH1 participate in the citric acid cycle. GABA showed a negative correlation with XPNPEP3.

The above results reveal biomarkers related to the differential efficacy of Telitacicept in treating SLE patients and potential mechanisms underlying these differences, which may provide a reference for personalized treatment and mechanistic research in SLE.

## Linked entities

- **Genes:** XPNPEP3 (X-prolyl aminopeptidase 3) [NCBI Gene 63929], SRSF5 (serine and arginine rich splicing factor 5) [NCBI Gene 6430], SRSF6 (serine and arginine rich splicing factor 6) [NCBI Gene 6431], WARS1 (tryptophanyl-tRNA synthetase 1) [NCBI Gene 7453], IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417], ITLN1 (intelectin 1) [NCBI Gene 55600]
- **Chemicals:** pyruvate (PubChem CID 107735), gamma-aminobutyric acid (PubChem CID 119), GABA (PubChem CID 119)
- **Diseases:** systemic lupus erythematosus (MONDO:0007915), SLE (MONDO:0007915)

## Full-text entities

- **Genes:** IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, ITLN1 (intelectin 1) [NCBI Gene 55600] {aka HL-1, HL1, INTL, ITLN, LFR, hIntL}, XPNPEP3 (X-prolyl aminopeptidase 3) [NCBI Gene 63929] {aka APP3, ICP55, NPHPL1}, SRSF6 (serine and arginine rich splicing factor 6) [NCBI Gene 6431] {aka B52, HEL-S-91, SFRS6, SRP55}, SRSF5 (serine and arginine rich splicing factor 5) [NCBI Gene 6430] {aka HRS, SFRS5, SRP40}
- **Diseases:** SLE (MESH:D008180)
- **Chemicals:** pyruvate (MESH:D019289), GABA (MESH:D005680), citric acid (MESH:D019343)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12996235/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12996235/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12996235/full.md

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Source: https://tomesphere.com/paper/PMC12996235