Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis

Rosenkranz, Margalit; Wilson, David C.; Marinov, Anthony; Decewicz, Alisha; Grof‐Tisza, Patrick; Kirchner, David; Giles, Brendan M.; Reynolds, Paul; Liebman, Michael; Kolli, V. S. Kumar; Thompson, Susan D.; Hirsch, Raphael

doi:10.1002/art.27447

Cited by 38 publications

(35 citation statements)

References 46 publications

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“…[24][25][26] Unlike synovial fluid, AH protein expression profiles did not seem to correlate with JIA subtype, however, the number of patients is too low for a reliable analysis. TTR was not identified in synovial fluid by other studies or in our SELDI-ToF MS experiments employing synovial fluids from patients with JIA (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

Ayuso

Boer

Byers

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the presence of biomarkers in aqueous humor (AH) from patients with uveitis associated with juvenile idiopathic arthritis (JIA).METHODS. AH (n ¼ 73) and serum (n ¼ 105) samples from 116 children were analyzed using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-ToF MS). The samples were divided into the following groups: JIA, silent chronic anterior uveitis (AU), other uveitis entities, and noninflammatory controls. Statistical biomarker identification was performed using the SELDI-ToF Biomarker Analysis Cluster Wizard followed by multivariate statistical analysis. Biochemical identification of biomarkers was performed by polyacrylamide gel protein separation, followed by liquid chromatography tandem mass spectrometry. ELISA was performed in a number of AH samples representing all four study groups.RESULTS. In the JIA group, one AH protein peak at mass/charge (m/z) 13,762 had qualitative and quantitative differences in expression compared with the other uveitis entities and the controls, but not to the group of silent chronic AU. Its quantitative expression in AH of patients with JIA and other silent chronic AU was positively associated with uveitis activity. The protein at m/z 13,762 in AH was identified as transthyretin (TTR). The TTR concentration in AH differed significantly between the study groups (P ¼ 0.006) with considerably higher TTR concentrations in JIA and silent chronic AU samples positive for m/z 13,762 than those of the other uveitis and control groups.CONCLUSIONS. TTR is a potential intraocular biomarker of JIA-associated uveitis. Its role in the pathogenesis of silent chronic AU with and without arthritis needs further investigation.

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Section: Discussionmentioning

confidence: 99%

Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

Ayuso

Boer

Byers

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…20 Haptoglobin has been found in arthritic synovial fluid (SF) and its local expression in inflamed joints was reported. 21,22 However, the function and structural modifications of Hp in arthritic SF are unclear. We hypothesized that a specifically modified Hp is formed in inflammatory environments such as RA and is involved in the induction of inflammation.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Identification of a specific haptoglobin C‐terminal fragment in arthritic synovial fluid and its effect on interleukin‐6 expression

Park

Kim

et al. 2013

Immunology

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SummaryHaptoglobin (Hp), a major acute-phase plasma protein, has been found in arthritic synovial fluid (SF). However, the function and structural modifications of Hp in arthritic SF are unknown. To investigate in vivo generation of modified Hp associated with inflammatory disease, we examined a new Hp isoform in SF from patients with rheumatoid arthritis (RA). Specific Hp fragments of 28 000 and 15 000 molecular weight were identified in SF of patients with RA, and the two polypeptides were presumed to be fragments of the Hp b-chain (43 000 MW) produced by cleavage with plasmin. The 15 000 MW fragment, which is a C-terminal region of Hp, was observed at higher frequency and levels in RA than in osteoarthritis. Plasmin activity was also higher in SF of RA patients. A recombinant 15 000 MW Hp fragment up-regulated interlukin-6 expression in monocytic cells. These findings indicate that the C-terminal Hp fragment is generated by plasmin in local inflammatory environments and acts as an inflammatory mediator. They further suggest that a specific Hp fragment might be applied as a novel biomarker for the diagnosis and prognosis of inflammatory diseases such as RA.

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“…Due to its close association with the synovial membrane on the one hand and the articular cartilage ECM on the other, SF composition is likely to most accurately reflect the nature and activity of physiological or pathological processes taking place in each (Rosenkranz et al 2010;Settle et al 2010). In addition, its continuous production and rapid clearance mean that SF composition is highly dynamic and thus sensitive to change, providing a real-time measure of ongoing disease activity.…”

Section: Biomarkersmentioning

confidence: 99%

Molecular monitoring of equine joint homeostasis

Grauw

2011

Veterinary Quarterly

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Diseases affecting synovial joints are a major cause of chronic disability both in humans and in companion animal species, most notably dogs and horses. As progressive deterioration of the articular cartilage is the hallmark of degenerative joint disease or osteoarthritis, research efforts traditionally tended to focus primarily on cartilage pathology. However, in recent years it has become clear that synovial joints should be considered intricate organs in their own right, with each of the constituent tissues (cartilage, bone, and synovial membrane) interacting with each other both in health and disease. Moreover, with the advent of modern molecular biology techniques, the importance of synovial inflammation in disease development and progression has become increasingly recognized. These realizations have spurred the need for tools that allow a more comprehensive, integral study of synovial joint homeostasis. This review provides a brief overview of synovial joint biology and the concept of joint homeostasis, followed by a discussion of methods that may be used to study joint homeostasis (varying from in vitro tissue culture to in vivo imaging) including specific advantages and limitations of each approach. It then zooms in on one such approach, synovial fluid biomarker analysis, as a promising avenue in synovial joint research, highlighting some results from equine studies performed in the author's own laboratory that illustrate how such studies may help shed light on in vivo joint homeostasis and therapeutic modulation thereof. The review concludes with some future perspectives and promising developments in the field.

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Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis

Cited by 38 publications

References 46 publications

Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

Identification of a specific haptoglobin C‐terminal fragment in arthritic synovial fluid and its effect on interleukin‐6 expression

Molecular monitoring of equine joint homeostasis

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