Application of a Novel Protein Biochip Technology for Detection and Identification of Rheumatoid Arthritis Biomarkers in Synovial Fluid

Uchida, Takafumi; Fukawa, Ai; Uchida, Mai; Fujita, Katsushi; Saito, Kenji

doi:10.1021/pr025531w

Cited by 98 publications

(67 citation statements)

References 19 publications

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“…The properties particular to these molecules, namely their small size, high stability, and low pI, make them especially amenable to SELDI-TOF MS analyses. Indeed, these proteins have been detected by this approach in a range of other clinical samples in which inflammation and/or infection were present (23,24 ).…”

Section: Discussionmentioning

confidence: 95%

Novel Neutrophil-Derived Proteins in Bronchoalveolar Lavage Fluid Indicate an Exaggerated Inflammatory Response in Pediatric Cystic Fibrosis Patients

et al. 2007

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Background: Airway inflammation in cystic fibrosis (CF) is exaggerated and characterized by neutrophil-mediated tissue destruction, but its genesis and mechanisms remain poorly understood. To further define the pulmonary inflammatory response, we conducted a proteome-based screen of bronchoalveolar lavage fluid (BALF) collected from young children with and without CF experiencing endobronchial infection. Methods: We collected BALF samples from 45 children younger than 5 years and grouped them according to the presence of respiratory pathogens: ≥1 × 105 colony-forming units (CFU)/mL BALF (18 and 12 samples with and without CF, respectively) and <1 × 105 CFU/mL (23 and 15 samples). BALF proteins were analyzed with SELDI-TOF mass spectrometry (MS) and H4 ProteinChips®. Proteins were identified and characterized using trypsin digestion, tandem MS, Fourier transform ion cyclotron resonance MS, immunoblotting, and ELISA. Results: The SELDI-TOF MS BALF profiles contained 53 unique, reliably detected proteins. Peak intensities of 24 proteins differed significantly between the CF and non-CF samples. They included the neutrophil proteins, α-defensin 1 and 2, S100A8, S100A9, and S100A12, as well as novel forms of S100A8 and S100A12 with equivalent C-terminal deletions. Peak intensities of these neutrophil proteins and immunoreactive concentrations of selected examples were significantly higher in CF than non-CF samples. Conclusions: Small neutrophil-derived BALF proteins, including novel C-terminal truncated forms of S100A proteins, are easily detected with SELDI-TOF MS. Concentrations of these molecules are abnormally high in early CF lung disease. The data provide new insights into CF lung disease and identify novel proteins strongly associated with CF airway inflammation.

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Section: Discussionmentioning

confidence: 95%

Novel Neutrophil-Derived Proteins in Bronchoalveolar Lavage Fluid Indicate an Exaggerated Inflammatory Response in Pediatric Cystic Fibrosis Patients

et al. 2007

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“…Putative SF markers discovered for RA include calgranulin B, calgranulin C, SAA, and myeloid-related protein 8 [428][429][430]. To confirm the finding about calgranulin B and to examine its applicability as a diagnostic marker, levels of the calgranulin A/B heterocomplex in plasma and in SF were further validated by immunoassays on patients of RA, OA, and other inflammatory joint diseases.…”

Section: Synovial Fluid (Sf)mentioning

confidence: 98%

Human body fluid proteome analysis

2006

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The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.

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“…High levels of CLP are observed in RA synovial fluid, even >5 mg/ml, and might differentiate RA from OA and other inflammatory arthritides. 47,[63][64][65][66] Notably, proteomic analysis has revealed the presence of S100A9 in synovial fluid from RA patients, but not in other disease controls. 67 CLP serum levels correlate with disease activity and are associated with markers of more severe RA in many studies.…”

Section: Clp In Rheumatic Diseasesmentioning

confidence: 99%

Calprotectin in rheumatic diseases

Ometto

Friso

Astorri

et al. 2016

Exp Biol Med (Maywood)

136

105

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Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment. AbstractCalprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-a inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker.

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Application of a Novel Protein Biochip Technology for Detection and Identification of Rheumatoid Arthritis Biomarkers in Synovial Fluid

Cited by 98 publications

References 19 publications

Novel Neutrophil-Derived Proteins in Bronchoalveolar Lavage Fluid Indicate an Exaggerated Inflammatory Response in Pediatric Cystic Fibrosis Patients

Novel Neutrophil-Derived Proteins in Bronchoalveolar Lavage Fluid Indicate an Exaggerated Inflammatory Response in Pediatric Cystic Fibrosis Patients

Human body fluid proteome analysis

Calprotectin in rheumatic diseases

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