ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2882

IgG Galactosylation Status Combined with MYOM2 SNP Precisely Predicts Anti-TNF Response in Ankylosing Spondylitis

Jing Liu1, Shifang Ren2, Zhenmin Niu1, Qi Zhu3, Wei Wan4, Jing Han2, Yanyun Ma5, Weilin Pu6, Yuan Li1, Xia Xu4, Yi Wang5, Dongbao Zhao4, Hui Zhang7, Feng Qian5, Xiaodong Zhou8, John D. Reveille9, Li Jin1,10, Dong-yi He3, Hejian Zou11,12, Jianxin Gu2 and Jiucun Wang10,12,13, 1State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China, 2Department of Biochemistry and Molecular Biology, Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, China, 3Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, Shanghai, China, 4Department of Rheumatology and Immunology, Changhai Hospital, Shanghai, China, 5Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China, 6State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences,, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China, Shanghai, China, 7School of Life Sciences, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China, 8Internal Medicine-Rheumatology, University of Texas McGovern Medical School, Houston, TX, 9University of Texas McGovern Medical School, Houston, TX, 10Fudan-Taizhou Institute of Health Sciences, Taizhou, China, 11Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China, 12Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China, 13State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, CN

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Tuesday, November 7, 2017

Title: Spondyloarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment IV

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder of spine and sacroiliac joints, which could lead to bony fusion of vertebral joints. TNF-blockers have a high efficacy in treating AS, yet up to 40% of AS patients show poor or even no response to this treatment. We aim to build an approach to predict the response prior to clinical treatment.

Methods: Ninety-two AS patients undergoing etanercept treatment were recruited and patients who did not fulfill BASDAI50 or ASAS40 at week 12 after starting treatment were considered poor-responders. The IgG galactosylation (IgG-Gal) ratio was calculated and candidate SNPs in patients treated with etanercept were examined. Machine-learning models and cross-validation were conducted to predict responsiveness.

Results: Both IgG-Gal ratio at each drug delivery and differential IgG-Gal ratios between week 0 and weeks 2, 4, 8, 12 showed significant differences between responders and poor-responders (Fig. 1A, B). AUC of the IgG-Gal ratio prediction model was 0.8 after cross-validation, significantly higher than current clinical indices, including CRP, ESR, BASDAI, BASFI and ASDAS. In addition, one MYOM2 SNP was found significantly associated with drug response (Table 1) (p=0.000576). Thus, a three-stage approach consisting of baseline IgG-Gal ratio, differential IgG-Gal ratio in 2 weeks, and the MYOM2 SNP genotype was conducted as follows (Fig. 2): Stage I: The IgG-Gal ratio of all AS patients were evaluated prior to etanercept treatment. Patients whose IgG-Gal ratio values were over 0.8 were predicted to be responders. Stage II: The others were examined after one dose of etanercept and repetitive IgG-Gal ratio evaluation was performed at week 2, among which patients whose ¦¤IgG-Gal ratio value were below -0.1 were predicted to be responders. Stage III: The remains were subjected to MYOM2 SNP genotyping, revealing patients with CT/TT genotype to be poor-responders and patients with CC genotype to be responders.

Conclusion: We propose a novel three-stage approach to combine genetic markers and post-translational modifications to predict precisely the response to the TNF blocker (Etanercept) in AS patients with an accuracy of 100% for poor-responders and 98% for responders.



Disclosure: J. Liu, None; S. Ren, None; Z. Niu, None; Q. Zhu, None; W. Wan, None; J. Han, None; Y. Ma, None; W. Pu, None; Y. Li, None; X. Xu, None; Y. Wang, None; D. Zhao, None; H. Zhang, None; F. Qian, None; X. Zhou, None; J. D. Reveille, Janssen, 5; L. Jin, None; D. Y. He, None; H. Zou, None; J. Gu, None; J. Wang, None.

To cite this abstract in AMA style:

Liu J, Ren S, Niu Z, Zhu Q, Wan W, Han J, Ma Y, Pu W, Li Y, Xu X, Wang Y, Zhao D, Zhang H, Qian F, Zhou X, Reveille JD, Jin L, He DY, Zou H, Gu J, Wang J. IgG Galactosylation Status Combined with MYOM2 SNP Precisely Predicts Anti-TNF Response in Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/igg-galactosylation-status-combined-with-myom2-snp-precisely-predicts-anti-tnf-response-in-ankylosing-spondylitis/. Accessed .

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