Proteome analysis reveals disease-associated marker proteins to differentiate RA patients from other inflammatory joint diseases with the potential to monitor anti-TNFα therapy

Drynda, Susanne; Ringel, Bruno; Kekow, Monika; Kühne, C; Drynda, Andreas; Glocker, Michael O.; Thiesen, Hans‐Jürgen; Kekow, Jörn

doi:10.1016/j.prp.2004.02.011

Cited by 82 publications

(59 citation statements)

References 21 publications

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“…Calprotectin serum levels correlate with disease activity, predict relapse, and are independently associated with radiographic progression in RA (12)(13)(14). Calprotectin serum levels decrease significantly after TNFi treatment (15), and therefore monitoring of the response to biologic therapy might be useful (16). Infliximab (IFX) significantly decreases calprotectin serum levels in RA patients, which is confirmed by immunohistochemical staining for MRP-8/MRP-14 on serial synovium sections, showing a progressive decrease in the number of infiltrating MRP-14-positive macrophages (17).…”

Section: Introductionmentioning

confidence: 99%

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

Inciarte-Mundo

Hernández

Ruíz-Esquide

et al. 2016

Arthritis Care & Research

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Objective. To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels. Methods. We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]). Results. Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ‡1 swollen joint (1.74 mg/ml versus 3.04 mg/ml; P 5 0.010). Using DAS28 ‡2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ‡2.47 mg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (r 5 20.671, P < 0.001) and IFX (r 5 20.729, P 5 0.017). Conclusion. Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acutephase reactants, even in patients with low inflammatory activity.

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Section: Introductionmentioning

confidence: 99%

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

Inciarte-Mundo

Hernández

Ruíz-Esquide

et al. 2016

Arthritis Care & Research

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“…In the case of 2D gel electrophoresis, S100A9, a small calcium-binding protein, was identified as a candidate diagnostic marker for rheumatoid arthritis by comparing the protein profiles of synovial fluid from rheumatoid arthritis and osteoarthritis patients 33 . In an analogous study using mass spectrometry, C-reactive protein and six members of the S100 protein family (including S100A9) were elevated in the synovial fluid of patients with erosive rheumatoid arthritis compared with that of patients with non-erosive rheumatoid arthritis 31 .…”

Section: Defining the Interactomementioning

confidence: 99%

“…Western blotting is a time-tested technique used in virtually all disciplines of biology. Straightforward protocols have been developed for studying nearly 800 different analytes simultaneously, taking advantage of the fact that proteins migrate at different molecular weights by gel electrophoresis 33 . Several examples of this technique have now been described for studying autoimmune disease, particularly rheumatoid arthritis 33 .…”

Section: Unbiased Proteomic Technologiesmentioning

confidence: 99%

“…Straightforward protocols have been developed for studying nearly 800 different analytes simultaneously, taking advantage of the fact that proteins migrate at different molecular weights by gel electrophoresis 33 . Several examples of this technique have now been described for studying autoimmune disease, particularly rheumatoid arthritis 33 . Lorenz and colleagues compared the proteome in the synovial tissue of patients with rheumatoid arthritis with that of patients with osteoarthritis 33 .…”

Section: Unbiased Proteomic Technologiesmentioning

confidence: 99%

“…Several examples of this technique have now been described for studying autoimmune disease, particularly rheumatoid arthritis 33 . Lorenz and colleagues compared the proteome in the synovial tissue of patients with rheumatoid arthritis with that of patients with osteoarthritis 33 . Comparison of the transcriptome and proteome revealed that only 28% of the mRNA and proteins correlated between the patient groups.…”

Section: Unbiased Proteomic Technologiesmentioning

confidence: 99%

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An array of possibilities for the study of autoimmunity

Fathman

Soares

Chan

et al. 2005

Nature

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Since the completion of the sequencing of the human genome, scientific focus has shifted from studying genes to analysing the much larger number of proteins encoded by them. Several proteins can be generated from a single gene depending on how the genetic information is read (transcribed) and how the resultant protein is modified following translation (post-translational modification). Genomic and proteomic technologies are already providing useful information about autoimmune disease, and they are likely to lead to important discoveries within the next decade.

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Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis

Wu¹,

Liu²,

Bemis³

et al. 2007

Arthritis & Rheumatism

152

112

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Objective. To identify potential molecular mediators and biomarkers for osteoarthritis (OA), through comparative proteomic analysis of articular cartilage tissue obtained from normal donors without OA (n ‫؍‬ 7) and patients with OA (n ‫؍‬ 7).Methods. The proteomic analyses comprised extraction of soluble proteins from cartilage, separation of the protein mixtures by sodium dodecyl sulfatepolyacrylamide gel electrophoresis followed by in-gel digestion, and subsequent nano-liquid chromatographytandem mass spectrometry analysis in conjunction with a database search for protein identification and semiquantitation.Results. A total of 814 distinct proteins were identified with high confidence from 14 samples; 420 of these proteins were detected with >3 unique peptides in at least 4 samples from the same group. Using stringent criteria, 59 proteins were found to be differentially expressed in OA cartilage. Gene Ontology and Ingenuity pathway analysis tools were used to characterize these proteins into functional categories. One of the upregulated proteins, HtrA1, a serine protease, was detected at high levels in cartilage.Conclusion. Altered protein expression in the disease state is associated with many aspects of the pathogenesis of OA, such as increased proteolysis, lipid metabolism, immune response, and decreased signal transduction. To our knowledge, this is the first time that a large portion of these proteins and their expression patterns were identified in cartilage, thus providing new insights for finding novel pathologic mediators and biomarkers of OA.

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Proteome analysis reveals disease-associated marker proteins to differentiate RA patients from other inflammatory joint diseases with the potential to monitor anti-TNFα therapy

Cited by 82 publications

References 21 publications

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

An array of possibilities for the study of autoimmunity

Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis

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