Dataset Information

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.

SUBMITTER: Liu J

PROVIDER: S-EPMC6567531 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Liu Jing J Zhu Qi Q Han Jing J Zhang Hui H Li Yuan Y Ma Yanyun Y He Dongyi D Gu Jianxin J Zhou Xiaodong X Reveille John D JD Jin Li L Zou Hejian H Ren Shifang S Wang Jiucun J

Molecular medicine (Cambridge, Mass.) 20190613 1

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31195969

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Project description:Methotrexate (MTX) is the standard first-line therapy in rheumatoid arthritis (RA) with variable clinical efficacy that is difficult to predict. The glycosylation status of immunoglobulin G (IgG) is altered in RA and influenced by MTX treatment. We aimed to further investigate if IgG glycosylation in untreated early RA can predict therapeutic response to MTX.We used a shotgun proteomic approach to screen for the Fc glycopeptides in the serum of 12 control subjects and 59 untreated patients with early RA prior to and following MTX initiation. MTX treatment response was defined according to the European League Against Rheumatism at a median of 14 weeks (range 13-15) after treatment initiation. Seropositive patients were defined as those testing positive for anticitrullinated protein antibodies and/or rheumatoid factor at baseline (n = 44). Data analysis was performed using uni- and multivariate statistics.We could confirm a low abundance of galactosylated glycans in untreated patients with early RA compared with control subjects that was partially restored by MTX treatment. This was more evident among future nonresponders than among responders to MTX treatment. Results were further validated and confirmed by multivariate statistical analysis of the baseline Fc glycan, proteomic, and clinical data. We found that the ratio between the main agalactosylated (FA2) and main mono- and di-galactosylated Fc glycans (FA2G1 and FA2G2) of IgG1 ranked as the most prominent factor distinguishing responders from nonresponders. A low baseline ratio of FA2/[FA2G1 + FA2G2]-IgG1 was associated with nonresponse (OR 5.3 [1.6-17.0]) and was able to discriminate future nonresponders from responders to MTX therapy with a sensitivity of 70% (95% CI 46-88%) and a specificity of 69% (95% CI 52-83%). For seropositive patients (n = 44), this trend was improved with a sensitivity of 73% (95% CI 45-92%) for nonresponse and a specificity of 79% (95% CI 60-92%).We show that the FA2/[FA2G1 + FA2G2] of IgG1 is a biomarker candidate that is significantly associated with nonresponding patients and has potential value for prediction of MTX clinical response.

Project description:BackgroundThis study aimed to identify the relationship between gait parameters and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS).MethodsThe study group comprised 134 patients with AS and 124 patients were enrolled as controls. All study participants underwent instrumented gait analysis and completed clinical questionnaires. The kinematic parameters of gait were walking speed, step length, cadence, stance phase, single support, double support, phase coordination index (PCI), and gait asymmetry (GA). For each patient, a visual analog scale (VAS; 0-10) score was used to assess back pain, 36-item short form survey (SF-36) questionnaire was administered to evaluate the HRQOL, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was calculated. Using kinematic parameters and questionnaires, statistical analyses were done to investigate significant differences between the groups. Relationship of gait kinematic data and questionnaires of clinical outcome was also evaluated.ResultsAmong the 134 patients with AS, 34 were women and 100 were men. In the control group, 26 were women and 98 were men. The patients with AS and control group patients had significant differences in terms of walking speed, step length, single support, PCI, and GA. However, such differences were not observed in cadence, stance phase, and double support (p > 0.05). In correlation analyses, gait kinematic parameters and clinical outcomes were significantly related with each other. In multiple regression analysis performed to identify predictive factors for clinical outcome, walking speed was found to predict VAS, and walking speed and step length were found to predict the BASDAI and SF-36 scores.ConclusionsPatients with and without AS had significant differences in the gait parameters. Correlation analysis showed significant correlation between the gait kinematic data and clinical outcomes. In particular, walking speed and step length successfully predicted clinical outcomes in patients with AS.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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