Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis

Chan Wang; Zhuye Qin; Mingming Zhang; Yaping Dai; Luyao Zhang; Wenyan Tian; Yuhua Gong; Sufang Chen; Can Yang; Ping Xu; Xingjuan Shi; Weifeng Zhao; Suraj Timilsina; M Eric Gershwin; Weichang Chen; Fang Qiu; Xiangdong Liu

doi:10.1016/j.jtauto.2024.100239

Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis

J Transl Autoimmun. 2024 Mar 20:8:100239. doi: 10.1016/j.jtauto.2024.100239. eCollection 2024 Jun.

Authors

Chan Wang^{1

2}, Zhuye Qin³, Mingming Zhang¹, Yaping Dai⁴, Luyao Zhang¹, Wenyan Tian⁵, Yuhua Gong⁶, Sufang Chen⁷, Can Yang⁸, Ping Xu⁴, Xingjuan Shi¹, Weifeng Zhao⁹, Suraj Timilsina¹⁰, M Eric Gershwin¹⁰, Weichang Chen⁵, Fang Qiu⁸, Xiangdong Liu¹

Affiliations

¹ Key Laboratory of Developmental Genes and Human Diseases, School of Life Sciences and Technology, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu, 210096, China.
² Institute of Translational Medicine, Medical College, Yangzhou University, 136 Yangjiang Middle Road, Yangzhou, Jiangsu, 225001, China.
³ Department of Laboratory Medicine, Southeast University Hospital, 82 Chengxian Street, Nanjing, Jiangsu, 210018, China.
⁴ Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, 1215 Guangrui Road, Wuxi, Jiangsu, 214000, China.
⁵ Department of Gastroenterology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, China.
⁶ Department of Laboratory Medicine, The Third People's Hospital of Zhenjiang, 300 Daijiamen, Zhenjiang, Jiangsu, 212021, China.
⁷ Department of Laboratory Medicine, The Fifth People's Hospital of Suzhou, Soochow University, 10 Guangqian Road, Suzhou, Jiangsu, 215131, China.
⁸ Department of Laboratory Medicine, The Fourth Affiliated Hospital of Nanjing Medical University, 298 Nanpu Road, Nanjing, Jiangsu, 210031, China.
⁹ Department of Hepatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
¹⁰ Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Genome and Biomedical Sciences Facility Building, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA.

Abstract

Objectives: Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear.

Materials and methods: Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296-386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients.

Results: In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.β = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.β = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease.

Conclusions: Our study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.

Keywords: Primary biliary cholangitis; Quantitation; UDCA; gp210; sp100.