Identifying Infliximab- (IFX-) Responsive Blood Signatures for the Treatment of Rheumatoid Arthritis

Ding, Shi‐Jian; Li, ZhanDong; Zeng, Tao; Zhang, Yuhang; Huang, Tao; Cai, Yu-Dong

doi:10.1155/2021/5556784

Cited by 1 publication

(2 citation statements)

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“…We boldly speculated that the USP16 and UHMK1 may influence LEF response in RA patients via the metabolic network. DISC1 , which encodes a scaffold protein, promotes hemoglobin synthesis in the peripheral blood ( 59 ). Several studies assessed the DISC1 contents in PBMCs of BD patients.…”

Section: Discussionmentioning

confidence: 99%

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The prognostic value of whole-genome DNA methylation in response to Leflunomide in patients with Rheumatoid Arthritis

Chen,

Wang,

Liu

et al. 2023

Front. Immunol.

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ObjectiveAlthough Leflunomide (LEF) is effective in treating rheumatoid arthritis (RA), there are still a considerable number of patients who respond poorly to LEF treatment. Till date, few LEF efficacy-predicting biomarkers have been identified. Herein, we explored and developed a DNA methylation-based predictive model for LEF-treated RA patient prognosis.MethodsTwo hundred forty-five RA patients were prospectively enrolled from four participating study centers. A whole-genome DNA methylation profiling was conducted to identify LEF-related response signatures via comparison of 40 samples using Illumina 850k methylation arrays. Furthermore, differentially methylated positions (DMPs) were validated in the 245 RA patients using a targeted bisulfite sequencing assay. Lastly, prognostic models were developed, which included clinical characteristics and DMPs scores, for the prediction of LEF treatment response using machine learning algorithms.ResultsWe recognized a seven-DMP signature consisting of cg17330251, cg19814518, cg20124410, cg21109666, cg22572476, cg23403192, and cg24432675, which was effective in predicting RA patient’s LEF response status. In the five machine learning algorithms, the support vector machine (SVM) algorithm provided the best predictive model, with the largest discriminative ability, accuracy, and stability. Lastly, the AUC of the complex model(the 7-DMP scores with the lymphocyte and the diagnostic age) was higher than the simple model (the seven-DMP signature, AUC:0.74 vs 0.73 in the test set).ConclusionIn conclusion, we constructed a prognostic model integrating a 7-DMP scores with the clinical patient profile to predict responses to LEF treatment. Our model will be able to effectively guide clinicians in determining whether a patient is LEF treatment sensitive or not.

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Section: Discussionmentioning

confidence: 99%

“…(A) simple model (B) complex model. encodes a scaffold protein, promotes hemoglobin synthesis in the peripheral blood (59). Several studies assessed the DISC1 contents in PBMCs of BD patients.…”

Section: B Amentioning

confidence: 99%