Proteomic analysis of plasma to reveal the impact of short-term etanercept therapy in pediatric patients with enthesitis-related arthritis: a case report.
In a variety of countries, juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in childhood, yet its etiology is still unknown. In recent years, etanercept, an effective inhibitor of tumor necrosis factor alpha (TNF-alpha), was used as an alternative in certain oligoarticular JIA patients resistant to conventional nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and corticosteroid therapies, and it resulted in sustained improvement in JIA symptoms. This pilot study explores the alterations of specific panels of cytokines and protein profiles in plasma for two Taiwanese pediatric cases with diagnosed enthesitis-related arthritis (ERA), a type of JIA. The patients were studied before and after taking etanercept alone, using a high-content screening approach employing membrane-based human cytokine antibody microarray and the conventional two-dimensional gel electrophoresis (2-DE) proteomic technique. Specifically, 2-DE in combination with mass spectrometry (MALDI-MS) revealed the functional roles of plasma proteins associated with the regulation of immune responses during short-term etanercept treatment of children with ERA. Our study shows that this biotherapy improved clinical ERA manifestations through the regulation of inflammatory mediators, including several cytotoxic cellular cytokines (IL-2/IFN-g), chemokines (MCP-1), and growth factors (GRO) that affect the expression of specific acute phase proteins such as haptoglobins, immunoglobulin A, and fibrinogen-gamma chain. Meanwhile, an up-regulation of antithrombin chain I, vitamin-D binding protein (VDBP), and the various apolipoproteins was also observed after the administration of etanercept in both studied children. These results may be interpreted as the relevant predictive biomarkers of therapeutic responses to etanercept. They suggest that etanercept, which is still rarely used in Taiwan, is a viable treatment for JIA patients, without adverse health effects and increased risk of secondary infections.
Chen
Ying-Chou
YC
Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital-Kaohsiung, Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Wang
Pei-Wen
PW
Pan
Tai-Long
TL
Bazylak
Grzegorz
G
Shen
Jiann-Jong
JJ
D001171:Arthritis, Juvenile / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis* / Q000276:immunology; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D000068800:Etanercept; D057166:High-Throughput Screening Assays; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010865:Pilot Projects; D011237:Predictive Value of Tests; D040901:Proteomics; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D001798:Blood Proteins; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept