Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases

Baillet, Athan; Trocmé, Candice; Berthier, Sylvie; Arlotto, Marie; Grange, Laurent; Chenau, Jérôme; Quétant, S.; Sève, Michel; Berger, François; Juvin, R.; Morel, Françoise; Gaudin, Philippe

doi:10.1093/rheumatology/kep452

Cited by 113 publications

(96 citation statements)

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“…Activated macrophages in the pannus tissue produce multiple factors that control both immunity and bone homeostasis, creating an imbalance between bone formation and bone resorption in favor of the latter, resulting in severe bone destruction (2,25). Of the various factors produced in the inflamed synovium, S100A8 and S100A9 are the most upregulated, and they are produced in excessive amounts (4)(5)(6). In the S100A8/A9 heterodimer complex, S100A8 is the active component, and S100A9 stabilizes S100A8 to prevent its degradation (7).…”

Section: Discussionmentioning

confidence: 99%

“…The "alarmins" S100A8 and S100A9, which are key players in the initiation and amplification of inflammatory responses (3), are the most up-regulated proteins present in RA synovial fluid, and they are significantly correlated with arthritis severity and joint degradation (4)(5)(6). S100 proteins are low molecular weight calcium-binding proteins produced mainly by monocytes, macrophages, and neutrophils and are secreted upon activation.…”

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confidence: 99%

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S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

Grevers¹,

Vries²,

Vogl³

et al. 2011

Arthritis & Rheumatism

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Objective. Rheumatoid arthritis, which is associated with elevated levels of S100A8 and S100A9, is characterized by severe bone erosions caused by enhanced osteoclast formation and activity. The aim of the present study was to investigate the role of S100A8 and S100A9 in osteoclastic bone destruction in murine antigen-induced arthritis (AIA).Methods. Bone destruction was analyzed in the arthritic knee joints of S100A9-deficient mice in which S100A8 protein expression was also lacking, and in wild-type (WT) controls. Osteoclast precursors from S100A9-deficient and WT mice were differentiated into osteoclasts in vitro. Additionally, precursors were stimulated with S100A8, S100A9, or S100A8/A9 during osteoclastogenesis. Receptor involvement was investigated using an anti-receptor for advanced glycation end products (anti-RAGE)-blocking antibody, soluble RAGE, or Toll-like receptor 4 (TLR-4)-deficient osteoclast precursors. The formation of osteoclasts and actin rings, the regulation of osteoclast markers, and bone resorption were analyzed.Results. Bone erosions and cathepsin K staining were significantly suppressed in S100A9-deficient mice after AIA induction. However, osteoclast precursors from S100A9-deficient mice developed normally into functional osteoclasts, which excludes a role for intrinsic S100A8/A9. In contrast to the results observed with S100A9 and S100A8/A9, the addition of S100A8 during osteoclastogenesis resulted in stimulation of osteoclast formation in conjunction with enhanced actin ring formation and increased bone resorption. Analysis of the putative receptor for S100A8 in osteoclastogenesis revealed that osteoclast differentiation and function could not be inhibited by blocking RAGE, whereas the increase in osteoclast numbers and enhanced bone resorption were completely abrogated using TLR-4-deficient osteoclast precursors.Conclusion. These results demonstrate that S100A8 stimulated osteoclast formation and activity and suggest that both S100A8 and TLR-4 are important factors in mediating osteoclastic bone destruction in experimental arthritis.Bone erosions are an important hallmark of rheumatoid arthritis (RA) and typically result from enhanced formation and activity of osteoclasts in affected joints. Osteoclasts originate from hematopoietic precursors of the monocyte/macrophage lineage that differentiate into multinucleated osteoclasts under the

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

Grevers¹,

Vries²,

Vogl³

et al. 2011

Arthritis & Rheumatism

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“…Importantly, HNP-levels in the synovial fluid were clearly higher in RA patients with erosive disease as opposed to non erosive disease in one study (4,374 ± 805 vs. 2,391 ± 946 ng/mL) [53]. Besides further suggesting a potential involvement in the pathogenesis, these findings indicate that HNP1-3 in the synovial fluid may also function as a biomarker for RA [52,53]. Interestingly, there was no correlation between synovial neutrophil counts and HNP1-3-levels in RA patients [52].…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 88%

“…HNP1-3 discriminated synovial fluid from patients with RA and osteoarthritis (OA) with a sensitivity of around 70% and a specificity of 56%. According to receiver operating characteristics analysis, the discriminative value was moderate (area under the curve of 66-70%) [52]. Importantly, HNP-levels in the synovial fluid were clearly higher in RA patients with erosive disease as opposed to non erosive disease in one study (4,374 ± 805 vs. 2,391 ± 946 ng/mL) [53].…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Vordenbäumen

Schneider

2011

Polymers

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Abstract:Defensins are small cationic peptides with antimicrobial properties. They constitute a highly conserved innate immune defense mechanism across species. Based on the arrangement of disulfide-bonds, α-and β-defensins are distinguished in humans. Both types of defensin comprise several distinct molecules that are preferentially expressed at epithelial surfaces and in blood cells. In the last decade, multiple immunomodulatory functions of defensins have been recognized, including chemotactic activity, the promotion of antigen presentation, and modulations of proinflammatory cytokine secretion. These findings suggested a role for defensins not only as a first line of defense, but also as connectors of innate and adaptive immune responses. Recently, increasingly accumulating evidence has indicated that defensins may also be involved in the pathogenesis of autoimmune rheumatic disorders such as systemic lupus erythematosus and rheumatoid arthritis. The current review summarizes the data connecting defensins to autoimmunity.

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“…Because the identity of proteins are not defined during this comparison, this technology cannot be used for the identification of antigens. However, some studies have used SELDI-TOF for fast screening of autoantigens in several autoimmune diseases, followed by additional MS for actual peptide identification (45)(46)(47)(48)(49)(50)(51). In this approach, antigen-antibody complexes are isolated from patient samples and immobilized on a SELDI chip prior to analysis of mass spectra.…”

Section: Surface Enhanced Laser Desorption/ionization -Time Of Flightmentioning

confidence: 99%

Immunoproteomics technologies in the discovery of autoantigens in autoimmune diseases

Ganesan

Ascherman

Minden

2016

Biomolecular Concepts

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Proteomics technologies are often used for the identification of protein targets of the immune system. Here, we discuss the immunoproteomics technologies used for the discovery of autoantigens in autoimmune diseases where immune system dysregulation plays a central role in disease onset and progression. These autoantigens and associated autoantibodies can be used as potential biomarkers for disease diagnostics, prognostics and predicting/monitoring drug responsiveness (theranostics). Here, we compare a variety of methods such as mass spectrometry (MS)-based [serological proteome analysis (SERPA), antibody mediated identification of antigens (AMIDA), circulating immune complexome (CIC) analysis, surface enhanced laser desorption/ionization-time of flight (SELDI-TOF)], nucleic acid based serological analysis of antigens by recombinant cDNA expression cloning (SEREX), phage immunoprecipitation sequencing (PhIP-seq) and array-based immunoscreening (proteomic microarrays), luciferase immunoprecipitation systems (LIPS), nucleic acid programmable protein array (NAPPA) methods. We also review the relevance of immunoproteomic data generated in the last 10 years, with a focus on the aforementioned MS based methods.

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Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases

Abstract: The most enhanced proteins in RA SF, the S100A8, S100A9 and S00A12 proteins, distinguished RA from MIA with high accuracy. Possible implication of resident cells in this increase may play a role in RA physiopathology.

Cited by 113 publications

References 40 publications

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Immunoproteomics technologies in the discovery of autoantigens in autoimmune diseases

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