Protein Biomarkers Predicting the Response to IFX+MTX+LEF Treatment in Patients with Rheumatoid Arthritis

Jian Chen ¹, Meng-shi Tang ², Li-chang Xu ³, Shu Li ², Yan Ge ², Jing Tian ², Xi Xie ², Jin-wei Chen ², Jin-feng Du ² and Fen Li¹, ¹Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China, Changsha, ²Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, ³International Department of YALI High School, Changsha

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Biomarkers, infliximab and drug therapy, proteomics, Rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 12, 2019

Title: RA – Treatments Poster III: Safety and Outcomes

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Patients with rheumatoid arthritis (RA) usually receive triple therapy with methotrexate (MTX), leflunomide (LEF) and infliximab (IFX), but nearly one-third of them do not respond to triple therapy. This study aimed to identify biomarkers for predicting the efficacy of triple therapy to optimize personalized treatment of RA.

Methods: All 20 enrolled patients met 2010 ACR/EULAR criteria for RA and were classified into good, moderate and non-responders (GR, MR, NR) for triple therapy. The Responders (R) were defined as the sum of GR and MR. Protein profiles of 4 responders and 4 non-responders were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and differentially expressed proteins (DEPs) with high-confidence peptides were validated in 15 responders and 5 non-responders by parallel response monitoring (PRM).

Results: iTRAQ identified 51 DEPs between responders and non-responders (p < 0.05, fold change > ± 1.2).The top five up-regulated DEPs were B7Z7M2, A0A087WZR4, Q53FL1, P08254 and G3V2V8, while the top five down-regulated proteins were Q6MZX9, B3KP77, P0DJI9, P0DJI8 and P02787. Targeted mass spectrometry by PRM identified 10 candidate biomarkers, and 3 DEPs including fibrinogen beta chain, epididymal secretory protein Li 282 and testicular tissue protein Li 70 were confirmed as predictive biomarkers.

Conclusion: This study demonstrated the feasibility of exploring biomarkers by applying iTRAQ and PRM mass spectrometry techniques, and a panel of biomarkers were identified to predict clinical response of IFX+MTX+LEF treatment in active RA patients.
This project was supported by the National Natural Science Foundation of China (No.81571599).

The workflow of proteomic analysis in this study. The study included candidate biomarkers discovering by iTRAQ and biomarkers confirmation by PRM. R, responders; NR, non-responders; iTRAQ, isobaric tags for relative and absolute quantification; PRM, parallel reaction monitoring

Hierarchical cluster of DEPs between R group and NR group, with folds > ±1.2 and P value <0.05. Rows represent the proteins and columns represent the group of patient. The relative expression level is indicated by the intensity of the color. Red, high expression; Blue, low expression. R, responder; NR, non-responder.

A- Comparison of 3 targeted DEPs. Fibrinogen beta chain, epididymal secretory protein Li 282 and testicular tissue protein Li 70 were up-regulated in R group as compared to NR group with P < 0.05. B- ROC curve of 3 targeted DEPs. AUC of the three predictive proteins was 0.720, 0.853 and 0.787, respectively. DEPs, Differentially expressed proteins; R, responder; NR, non-responder; ROC, relative operating characteristic. AUC, Area under the curve. C- Heatmap of 3 targeted DEPs in 15 responders -R- and 5 non-responders -NR-. The color indicated the relative expression level. Green: 0.5; white: 1, and red: 2.

Disclosure: J. Chen, None; M. Tang, None; L. Xu, None; S. Li, None; Y. Ge, None; J. Tian, None; X. Xie, None; J. Chen, None; J. Du, None; F. Li, None.

To cite this abstract in AMA style:

Chen J, Tang M, Xu L, Li S, Ge Y, Tian J, Xie X, Chen J, Du J, Li F. Protein Biomarkers Predicting the Response to IFX+MTX+LEF Treatment in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/protein-biomarkers-predicting-the-response-to-ifxmtxlef-treatment-in-patients-with-rheumatoid-arthritis/. Accessed .

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