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Open Access Highly Accessed Research article

Serum protein profile in systemic-onset juvenile idiopathic arthritis differentiates response versus nonresponse to therapy

Takako Miyamae1, David E Malehorn2, Bonnie Lemster1, Masaaki Mori3, Tomoyuki Imagawa3, Shumpei Yokota3, William L Bigbee2, Manda Welsh2, Klaus Klarskov4, Norihiro Nishomoto5, Abbe N Vallejo1 and Raphael Hirsch1*

Author Affiliations

1 Division of Rheumatology, Children's Hospital of Pittsburgh, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213

2 University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213

3 Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Japan

4 Départment de Phamacologie, Faculté de Medicine, Université de Sherbrooke, Québec, Canada

5 Osaka University, Osaka, Japan

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Arthritis Research & Therapy 2005, 7:R746-R755  doi:10.1186/ar1723

Published: 4 April 2005

Abstract

Systemic-onset juvenile idiopathic arthritis (SJIA) is a disease of unknown etiology with an unpredictable response to treatment. We examined two groups of patients to determine whether there are serum protein profiles reflective of active disease and predictive of response to therapy. The first group (n = 8) responded to conventional therapy. The second group (n = 15) responded to an experimental antibody to the IL-6 receptor (MRA). Paired sera from each patient were analyzed before and after treatment, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Despite the small number of patients, highly significant and consistent differences were observed before and after response to therapy in all patients. Of 282 spectral peaks identified, 23 had mean signal intensities significantly different (P < 0.001) before treatment and after response to treatment. The majority of these differences were observed regardless of whether patients responded to conventional therapy or to MRA. These peaks represent potential biomarkers of active disease. One such peak was identified as serum amyloid A, a known acute-phase reactant in SJIA, validating the SELDI-TOF MS platform as a useful technology in this context. Finally, profiles from serum samples obtained at the time of active disease were compared between the two patient groups. Nine peaks had mean signal intensities significantly different (P < 0.001) between active disease in patients who responded to conventional therapy and in patients who failed to respond, suggesting a possible profile predictive of response. Collectively, these data demonstrate the presence of serum proteomic profiles in SJIA that are reflective of active disease and suggest the feasibility of using the SELDI-TOF MS platform used as a tool for proteomic profiling and discovery of novel biomarkers in autoimmune diseases.