Effect of Telitacicept on Circulating Gd-IgA1 and IgA-Containing Immune Complexes in IgA Nephropathy

Jincan Zan; Lijun Liu; Guisen Li; Hongguang Zheng; Nan Chen; Caili Wang; Deqiong Xie; Li Zuo; Rongshan Li; Pengfei Zhang; Yue Wang; Wenxiang Wang; Lin Li; Jianmin Fang; Jicheng Lv; Hong Zhang

doi:10.1016/j.ekir.2024.01.003

Effect of Telitacicept on Circulating Gd-IgA1 and IgA-Containing Immune Complexes in IgA Nephropathy

Kidney Int Rep. 2024 Jan 10;9(4):1067-1071. doi: 10.1016/j.ekir.2024.01.003. eCollection 2024 Apr.

Authors

Jincan Zan¹, Lijun Liu¹, Guisen Li², Hongguang Zheng³, Nan Chen⁴, Caili Wang⁵, Deqiong Xie⁶, Li Zuo⁷, Rongshan Li⁸, Pengfei Zhang⁹, Yue Wang¹⁰, Wenxiang Wang¹¹, Lin Li¹¹, Jianmin Fang¹², Jicheng Lv¹, Hong Zhang¹

Affiliations

¹ Renal Division, Peking University First Hospital Peking University Institute of Nephrology Key Laboratory of Renal Disease, Ministry of Health of China Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education. Research Units of Diagnosis and Treatment of Immune-mediate Kidney Disease, Chinese Academy of Medical Sciences, Beijing, China.
² Renal Division and Institute of Nephrology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan, China.
³ Department of Nephrology, General Hospital of Northern Theater Command, Shenyang, China.
⁴ Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ The First Afﬁliated Hospitals of Baotou Medical College, Inner Mongolia University of Science and Technology, China.
⁶ Division of Nephrology, The Second People's Hospital of Yibin, Yibin, China.
⁷ Department of Nephrology, Peking University People's Hospital, Beijing, China.
⁸ Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan, China.
⁹ Department of Nephrology, Heping Hospital Afﬁliated to Changzhi Medical College, Shanxi, China.
¹⁰ Department of Nephrology, Peking University Third Hospital, Beijing, China.
¹¹ RemeGen Co., Ltd., Yantai Shandong, China.
¹² School of Life Science and Technology, Tongji University, Shanghai, China.

Abstract

Introduction: Telitacicept, a transmembrane activator and cyclophilin ligand interactor (TACI) fusion protein targeting B cell activating factor and a proliferation-inducing ligand (APRIL), has proven efficacy in treating Immunoglobulin A (IgA) nephropathy (IgAN). However, serum biomarkers that could predict the clinical response during the treatment remain unclear.

Methods: Plasma samples from 24 participants in the phase 2 clinical trial were collected at baseline and after 4, 12, and 24 weeks; with 8 participants in the placebo group, 9 in the 160 mg group, and 7 in the 240 mg group. We measured the levels of galactose-deficient-IgA1 (Gd-IgA1), IgA-containing immune complexes, C3a, C5a, and sC5b-9. The association between the changes in these markers and proteinuria reduction was analyzed.

Results: After 24 weeks of treatment, Gd-IgA1 decreased by 43.9% (95% confidence interval: 29.8%, 55.1%), IgG-IgA immune complex by 31.7% (14.4%, 45.5%), and poly-IgA immune complex by 41.3% (6.5%, 63.1%) in the 160 mg group; Gd-IgA1 decreased by 50.4% (38.6%, 59.9%), IgG-IgA immune complex decreased by 42.7% (29.5%, 53.4%), and poly-IgA immune complex decreased by 67.2% (48.5%,79.1%) in the 240 mg group. There were no significant changes in the circulatory C3a, C5a, or sC5b-9 levels during telitacicept treatment. Decreases in both plasma Gd-IgA1 and IgG-IgA or poly-IgA immune complexes were associated with proteinuria reduction. In turn, IgG-IgA or poly-IgA immune complexes showed a dose-dependent effect, consistent with proteinuria reduction during telitacicept treatment.

Conclusion: Telitacicept lowered both circulating Gd-IgA1 and IgA-containing immune complexes, whereas IgA immune complex levels were more consistent with decreased proteinuria.

Keywords: Gd-IgA1; IgA immune complexes; IgA nephropathy; TACI; biomarker; telitacicept.