Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis

Abstract Background This study aimed to investigate the expression profile of immune response-related proteins of Behcet’s disease (BD) patients and identify potential biomarkers for this disease. Methods Plasma was collected from BD patients and healthy controls (HC). Immune response-related protei...

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Main Authors: Huan Liu, Panpan Zhang, Fuzhen Li, Xiao Xiao, Yinan Zhang, Na Li, Liping Du, Peizeng Yang
Format: Article
Language:English
Published: BMC 2023-06-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13075-023-03074-y
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author Huan Liu
Panpan Zhang
Fuzhen Li
Xiao Xiao
Yinan Zhang
Na Li
Liping Du
Peizeng Yang
author_facet Huan Liu
Panpan Zhang
Fuzhen Li
Xiao Xiao
Yinan Zhang
Na Li
Liping Du
Peizeng Yang
author_sort Huan Liu
collection DOAJ
description Abstract Background This study aimed to investigate the expression profile of immune response-related proteins of Behcet’s disease (BD) patients and identify potential biomarkers for this disease. Methods Plasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method. Results Proteomics results showed 43 DEPs between BD patients and HC (P < 0.05). These DEPs were mainly involved in the Toll-like receptor 9 and NF-κB signaling pathways. Five models were constructed using DEPs [interleukin 10 (IL10), Fc receptor like 3 (FCRL3), Mannan-binding lectin serine peptidase 1 (MASP1), NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2), FAM3 metabolism regulating signaling molecule B (FAM3B), and O-6-methylguanine-DNA methyltransferase (MGMT)]. Among these models, the neural network model showed the best performance (AUC = 0.856, recall: 0.692, specificity: 0.857, precision: 0.900, accuracy: 0.750, F1 score: 0.783). BD patients were divided into two subtypes according to the consensus clustering method: one with high disease activity in association with higher expression of tripartite motif-containing 5 (TRIM5), SH2 domain-containing 1A (SH2D1A), phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), hematopoietic cell-specific Lyn substrate 1 (HCLS1), and DNA fragmentation factor subunit alpha (DFFA) and the other with low disease activity in association with higher expression of C–C motif chemokine ligand 11 (CCL11). Conclusions Our study not only revealed a distinctive immune response-related protein profile for BD but also showed that IL10, FCRL3, MASP1, NF2, FAM3B, and MGMT could serve as potential immune biomarkers for this disease. Additionally, a novel molecular disease classification model was constructed to identify subsets of BD.
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spelling doaj.art-647fb5ab03af4c10a2a22db59927c2fe2023-06-04T11:35:20ZengBMCArthritis Research & Therapy1478-63622023-06-0125111310.1186/s13075-023-03074-yIdentification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysisHuan Liu0Panpan Zhang1Fuzhen Li2Xiao Xiao3Yinan Zhang4Na Li5Liping Du6Peizeng Yang7Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury RepairDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury RepairDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury RepairDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury RepairDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury RepairDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury RepairDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury RepairAbstract Background This study aimed to investigate the expression profile of immune response-related proteins of Behcet’s disease (BD) patients and identify potential biomarkers for this disease. Methods Plasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method. Results Proteomics results showed 43 DEPs between BD patients and HC (P < 0.05). These DEPs were mainly involved in the Toll-like receptor 9 and NF-κB signaling pathways. Five models were constructed using DEPs [interleukin 10 (IL10), Fc receptor like 3 (FCRL3), Mannan-binding lectin serine peptidase 1 (MASP1), NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2), FAM3 metabolism regulating signaling molecule B (FAM3B), and O-6-methylguanine-DNA methyltransferase (MGMT)]. Among these models, the neural network model showed the best performance (AUC = 0.856, recall: 0.692, specificity: 0.857, precision: 0.900, accuracy: 0.750, F1 score: 0.783). BD patients were divided into two subtypes according to the consensus clustering method: one with high disease activity in association with higher expression of tripartite motif-containing 5 (TRIM5), SH2 domain-containing 1A (SH2D1A), phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), hematopoietic cell-specific Lyn substrate 1 (HCLS1), and DNA fragmentation factor subunit alpha (DFFA) and the other with low disease activity in association with higher expression of C–C motif chemokine ligand 11 (CCL11). Conclusions Our study not only revealed a distinctive immune response-related protein profile for BD but also showed that IL10, FCRL3, MASP1, NF2, FAM3B, and MGMT could serve as potential immune biomarkers for this disease. Additionally, a novel molecular disease classification model was constructed to identify subsets of BD.https://doi.org/10.1186/s13075-023-03074-yBehcet’s diseaseUveitisImmuneProteomicsBiomarker
spellingShingle Huan Liu
Panpan Zhang
Fuzhen Li
Xiao Xiao
Yinan Zhang
Na Li
Liping Du
Peizeng Yang
Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis
Arthritis Research & Therapy
Behcet’s disease
Uveitis
Immune
Proteomics
Biomarker
title Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis
title_full Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis
title_fullStr Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis
title_full_unstemmed Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis
title_short Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis
title_sort identification of the immune related biomarkers in behcet s disease by plasma proteomic analysis
topic Behcet’s disease
Uveitis
Immune
Proteomics
Biomarker
url https://doi.org/10.1186/s13075-023-03074-y
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