IgG Galactosylation status combined with MYOM2-rs2294066 precisely predicts anti-TNF response in ankylosing spondylitis.

Abstract

BACKGROUND:

Tumor necrosis factor (TNF) blockers have a high efficacy in treating Ankylosing Spondylitis (AS), yet up to 40% of AS patients show poor or even no response to this treatment. In this paper, we aim to build an approach to predict the response prior to clinical treatment.

METHODS:

AS patients during the active progression were included and treated with TNF blocker for 3 months. Patients who do not fulfill ASASAS40 were considered as poor responders. The Immunoglobulin G galactosylation (IgG-Gal) ratio representing the quantity of IgG galactosylation was calculated and candidate single nucleotide polymorphisms (SNPs) in patients treated with etanercept was obtained. Machine-learning models and cross-validation were conducted to predict responsiveness.

RESULTS:

Both IgG-Gal ratio at each time point and differential IgG-Gal ratios between week 0 and weeks 2, 4, 8, 12 showed significant difference between responders and poor-responders. Area under curve (AUC) of the IgG-Gal ratio prediction model was 0.8 after cross-validation, significantly higher than current clinical indexes (C-reactive protein (CRP) = 0.65, erythrocyte sedimentation rate (ESR) = 0.59). The SNP MYOM2-rs2294066 was found to be significantly associated with responsiveness of etanercept treatment. A three-stage approach consisting of baseline IgG-Gal ratio, differential IgG-Gal ratio in 2 weeks, and rs2294066 genotype demonstrated the ability to precisely predict the response of anti-TNF therapy (100% for poor-responders, 98% for responders).

CONCLUSIONS:

Combination of different omics can more precisely to predict the response of TNF blocker and it is potential to be applied clinically in the future.

• Authors: Jing Liu, Qi Zhu, Jing Han, Hui Zhang, Yuan Li, Yanyun Ma, Dongyi He, Jianxin Gu, Xiaodong Zhou, John D Reveille, Li Jin, Hejian Zou, Shifang Ren, Jiucun Wang
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) Vol. 25 Issue 1 Pg. 25 (06 13 2019) ISSN: 1528-3658 [Electronic] England
• PMID: 31195969 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Connectin
• Immunoglobulin G
• MYOM2 protein, human
• Tumor Necrosis Factor-alpha
• glycosylated IgG
• Etanercept

Topics

• Adult
• Antirheumatic Agents (therapeutic use)
• Blood Sedimentation (drug effects)
• Connectin (genetics)
• Etanercept (therapeutic use)
• Female
• Genotype
• Glycosylation
• Humans
• Immunoglobulin G (metabolism)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Spondylitis, Ankylosing (drug therapy, genetics)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)