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

IF 4.7 Q2 IMMUNOLOGY
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
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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.

GP210 自身抗体是衡量原发性胆汁性胆管炎 UDCA 反应的一个指标
目的gp210和sp100抗体是与原发性胆汁性胆管炎(PBC)相关的特异性和独特的抗核自身抗体(ANA)。重要的是,出现抗 gp210 和抗 sp100 反应表明临床疗效不佳。材料和方法我们使用内部纯化的 gp210(HSA108-C18)和 sp100(氨基酸位置 296-386),在 390 例 PBC 患者(包括 259 例之前未接受熊去氧胆酸(UDCA)治疗的患者和 131 例接受过 UDCA 治疗的患者)中使用化学发光免疫分析法(CLIA)定量测定了血清中的 gp210 和 sp100 自身抗体。结果在横断面分析中,我们分别在 390 例 PBC 患者中的 129 例(33.1%)和 80 例(20.5%)中检测到了抗 gp210 免疫球蛋白 G (IgG) 和抗 sp100 IgG 自身抗体。多变量分析显示,基线时的血清 IgG(st.β = 0.35,P = 0.003)和γ-谷氨酰转移酶(GGT)(st.β = 0.23,P = 0.042)水平与抗 gp210 浓度独立相关。在连续测试中,我们观察到抗 gp210 抗体水平有明显波动。这些波动反映了对 UDCA 治疗的反应性,尤其是在抗 gp210 阳性患者中,在疾病的不同阶段,抗 gp210 抗体的浓度最初较低。我们建议对这些独特的 ANA 进行更详细、更长期的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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