Calprotectin in Rheumatoid Arthritis

Miriam García-Arias , Dora Pascual-Salcedo , Susana Ramiro , Marie-Eve Ueberschlag , Thomas M. Jermann , Carlos Cara , Emilio Martín-Mola , Alejandro Balsa

Proinflammatory S100A12 Can Activate Human Monocytes via Toll-like Receptor 4

Dirk Foell , Helmut Wittkowski , Christoph Kessel , Aloys Lüken , Toni Weinhage , Georg Varga , Thomas Vogl , Timo Wirth , Dorothee Viemann , Per Björk , Marieke A. D. van Zoelen , Faekah Gohar , Geetha Srikrishna , Matthias Kraft , Johannes Roth

MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis

I. Y. Choi , D. M. Gerlag , M. J. Herenius , R. M. Thurlings , C. A. Wijbrandts , D. Foell , T. Vogl , J. Roth , P. P. Tak , D. Holzinger

Myeloid-Related Proteins 8 and 14 Contribute to Monosodium Urate Monohydrate Crystal-Induced Inflammation in Gout

Dirk Holzinger , Nadine Nippe , Thomas Vogl , Kristina Marketon , Vijayashree Mysore , Toni Weinhage , Nicola Dalbeth , Bregina Pool , Tony Merriman , Dominique Baeten , Annette Ives , Nathalie Busso , Dirk Foell , Sylvette Bas , Cem Gabay , Johannes Roth

Validation of Relapse Risk Biomarkers for Routine Use in Patients With Juvenile Idiopathic Arthritis

Friederike Rothmund , Joachim Gerss , Nicolino Ruperto , Jan Däbritz , Helmut Wittkowski , Michael Frosch , Nico M. Wulffraat , Lucy R. Wedderburn , Dirk Holzinger , Faekah Gohar , Sebastiaan J. Vastert , Riva Brik , Chantal Job Deslandre , Jose Antonio Melo-Gomes , Claudia Saad Magalhães , Roberto Barcellona , Ricardo Russo , Marco Gattorno , Alberto Martini , Johannes Roth , Dirk Foell

Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort

Liesbet Van Praet , Lennart Jans , Philippe Carron , Peggy Jacques , Elien Glorieus , Roos Colman , Heleen Cypers , Herman Mielants , Martine De Vos , Claude Cuvelier , Filip Van den Bosch , Dirk Elewaut

Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity

Thomas Vogl , Michel Eisenblätter , Tom Völler , Stefanie Zenker , Sven Hermann , Peter van Lent , Andreas Faust , Christiane Geyer , Beatrix Petersen , Kirsten Roebrock , Michael Schäfers , Christoph Bremer , Johannes Roth

Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity

Thomas Vogl , Michel Eisenblätter , Tom Völler , Stefanie Zenker , Sven Hermann , Peter van Lent , Andreas Faust , Christiane Geyer , Beatrix Petersen , Kirsten Roebrock , Michael Schäfers , Christoph Bremer , Johannes Roth

Alarmins S100A8/S100A9 aggravate osteophyte formation in experimental osteoarthritis and predict osteophyte progression in early human symptomatic osteoarthritis

R. F. P. Schelbergen , W. de Munter , M. H. J. van den Bosch , F. P. J. G. Lafeber , A. Sloetjes , T. Vogl , J. Roth , W. B. van den Berg , P. M. van der Kraan , A. B. Blom , P. L. E. M. van Lent

The Thymic Microenvironment Differentially Regulates Development and Trafficking of Invariant NKT Cell Sublineages

M. B. Drennan , S. Govindarajan , K. De Wilde , S. M. Schlenner , C. Ware , S. Nedospasov , H.-R. Rodewald , D. Elewaut

A clinically based protein discovery strategy to identify potential biomarkers of response to anti-TNF-α treatment of psoriatic arthritis

Emily S. Collins , Aisha Q. Butt , David S. Gibson , Michael J. Dunn , Ursula Fearon , Arno W. van Kuijk , Danielle M. Gerlag , Eliza Pontifex , Douglas J. Veale , Paul P. Tak , Oliver FitzGerald , Stephen R. Pennington

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis

Angela Mc Ardle , Brian Flatley , Stephen R. Pennington , Oliver FitzGerald

Psoriatic Arthritis Under a Proteomic Spotlight: Application of Novel Technologies to Advance Diagnosis and Management

Aisha Q. Butt , Angela McArdle , David S. Gibson , Oliver FitzGerald , Stephen R. Pennington

MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis

Janneke Anink , Lisette W. A. Van Suijlekom-Smit , Marieke H. Otten , Femke H. M. Prince , Marion A. J. van Rossum , Koert M. Dolman , Esther P. A. H. Hoppenreijs , Rebecca ten Cate , Simona Ursu , Lucy R. Wedderburn , Gerd Horneff , Michael Frosch , Thomas Vogl , Faekah Gohar , Dirk Foell , Johannes Roth , Dirk Holzinger

Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis

H Cypers , G Varkas , S Beeckman , K Debusschere , T Vogl , J Roth , M B Drennan , M Lavric , D Foell , C A Cuvelier , M De Vos , J Delanghe , F Van den Bosch , D Elewaut

Commensal microbiota influence systemic autoimmune responses

J. T. Van Praet , E. Donovan , I. Vanassche , M. B. Drennan , F. Windels , A. Dendooven , L. Allais , C. A. Cuvelier , F. van de Loo , P. S. Norris , A. A. Kruglov , S. A. Nedospasov , S. Rabot , R. Tito , J. Raes , V. Gaboriau-Routhiau , N. Cerf-Bensussan , T. Van de Wiele , G. Eberl , C. F. Ware , D. Elewaut

Alarmins S100A8/S100A9 aggravate osteophyte formation in experimental osteoarthritis and predict osteophyte progression in early human symptomatic osteoarthritis

R F P Schelbergen , W de Munter , M H J van den Bosch , F P J G Lafeber , A Sloetjes , T Vogl , J Roth , W B van den Berg , P M van der Kraan , A B Blom , P L E M van Lent

Translationale Forschung in der pädiatrischen Rheumatologie

K. Lippitz , J. Waldkirch , C. Kessel , G. Varga , D. Foell

MAIT cells – not just another brick in the wall

Debusschere K, Lories R, Elewaut D.

S100A8/A9, a potent serum and molecular imaging biomarker for synovial inflammation and joint destruction in seronegative experimental arthritis

Geven EJW, van den Bosch MHJ, Di Ceglie I, Ascone G, Abdollahi-Roodsaz S, Sloetjes AW, Hermann S, Schäfers M, van de Loo FAJ, van der Kraan PM, Koenders MI, Foell D, Roth J, Vogl T, van Lent PL

Alarmins firing arthritis: Helpful diagnostic tools and promising therapeutic targets. Joint Bone Spine

Lavric M, Miranda-Garcia MA, Holzinger D, Foell D, Witkowski Helmut

Developing Clinically Relevant Biomarkers in Inflammatory Arthritis: A Multi-Platform Approach for Serum Candidate Protein Discovery

To identify candidate biomarkers that have the potential to distinguish between patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA) and explore the value of combining different protein discovery platforms for the development of a multiplexed protein biomarker panel.

Management of juvenile idiopathic arthritis: hitting the target.

The treatment of juvenile idiopathic arthritis (JIA) is evolving. The growing number of effective drugs has led to successful treatment and prevention of long-term sequelae in most patients. Although patients with JIA frequently achieve lasting clinical remission, sustained remission off medication is still elusive for most. Treatment approaches vary substantially among paediatric rheumatologists owing to the inherent heterogeneity of JIA and, until recently, to the lack of accepted and well-evidenced guidelines. Furthermore, many pertinent questions related to patient management remain unanswered, in particular regarding treatment targets, and selection, intensity and sequence of initiation or withdrawal of therapy. Existing JIA guidelines and recommendations do not specify treat-to-target or tight control strategies, in contrast to adult rheumatology in which these approaches have been successful. The concepts of window of opportunity (early treatment to improve long-term outcomes) and immunological remission (abrogation of subclinical disease activity) are also fundamental when defining treatment methodologies. This Review explores the application of these concepts to JIA and their possible contribution to the development of future clinical guidelines or consensus treatment protocols. The article also discusses how diverse forms of standardized, guideline-led care and personalized treatment can be combined into a targeted, patient-centred approach to optimize management strategies for patients with JIA.

Reprogramming of Monocfytes by GM-CSF Contributes to Regulatory Immune Functions during Intestinal Inflammation

Human and murine studies showed that GM-CSF exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF–activated monocytes (GMaMs) in vivo. We used microarray technology and functional assays to characterize GMaMs in vitro and used a mouse model of colitis to study GMaM functions in vivo. GM-CSF activates monocytes to increase adherence, migration, chemotaxis, and oxidative burst in vitro, and primes monocyte response to secondary microbial stimuli. In addition, GMaMs accelerate epithelial healing in vitro. Most important, in a mouse model of experimental T cell–induced colitis, GMaMs show therapeutic activity and protect mice from colitis. This is accompanied by increased production of IL-4, IL-10, and IL-13, and decreased production of IFN-γ in lamina propria mononuclear cells in vivo. Confirming this finding, GMaMs attract T cells and shape their differentiation toward Th2 by upregulating IL-4, IL-10, and IL-13 in T cells in vitro. Beneficial effects of GM-CSF in Crohn’s disease may possibly be mediated through reprogramming of monocytes to simultaneously improved bacterial clearance and induction of wound healing, as well as regulation of adaptive immunity to limit excessive inflammation.

MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis

One-third of rheumatoid arthritis (RA) patients treated with biological therapy show lack of response. The use of predictive biomarkers to identify responders to treatment may provide guidance in optimising treatment strategies and reduce unnecessary side effects and costs.

Validation of Relapse Risk Biomarkers for Routine Use in Patients With Juvenile Idiopathic Arthritis

The myeloid-related proteins 8 and 14 (MRP-8/MRP-14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme-linked immunosorbent assays (ELISAs) in order to validate systems available for routine use.

A5.13 Serum levels of S100A8/A9 complex and corticosterone correlate to synovial inflammation and cartilage/bone damage in IL-1RA-/-MICE, a model system for seronegative arthritis

In seronegative arthritis high levels of the alarmins S100A8 and S100A9 are measured in serum. These alarmins are released by activated macrophages and can mediate cartilage and bone destruction. Additionally, glucocorticoids have been implicated to stimulate S100A8 and S100A9 synthesis. The aim of this study is to identify serum S100A8/A9 complex as a potential biomarker for joint destruction in seronegative arthritis using IL-1Ra-/- mice as an experimental model and whether serum S100A8/A9 levels are associated with serum corticosterone (CORT) levels.

Pro-inflammatory S100A12 can activate human monocytes via Toll-like receptor 4.

Dirk Foell, Helmut Wittkowski, Christoph Kessel, Aloys Lüken, Toni Weinhage, Georg Varga, Thomas Vogl, Timo Wirth, Dorothee Viemann, Per Björk, Marieke A. D. van Zoelen, Faekah Gohar, Geetha Srikrishna, Matthias Kraft, and Johannes Roth
AJRCCM Articles in Press. Published on 23-April-2013 as 10.1164/rccm.201209-1602OC

Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study.

Gerss J, Roth J, Holzinger D, Ruperto N, Wittkowski H, Frosch M, Wulffraat N, Wedderburn L, Stanevicha V, Mihaylova D, Harjacek M, Len C, Toppino C, Masi M, Minden K, Saurenmann T, Uziel Y, Vesely R, Apaz MT, Kuester RM, Elorduy MJ, Burgos-Vargas R, Ioseliani M, Magni-Manzoni S, Unsal E, Anton J, Balogh Z, Hagelberg S, Mazur-Zielinska H, Tauber T, Martini A, Foell D; Paediatric Rheumatology International Trials Organization (PRINTO).
Ann Rheum Dis. 2012 Dec;71(12):1991-7. doi: 10.1136/annrheumdis-2012-201329. Epub 2012 Jun 11.

Improving Relapse Prediction in Inflammatory Bowel Disease by Neutrophil-Derived S100A12.

Däbritz J, Langhorst J, Lügering A, Heidemann J, Mohr M, Wittkowski H, Krummenerl T, Foell D.
Inflamm Bowel Dis. 2013 May;19(6):1130-1138.

Peripheral monocyte functions and activation in patients with quiescent Crohn's disease.

Schwarzmaier D, Foell D, Weinhage T, Varga G, Däbritz J.
PLoS One. 2013 Apr 26;8(4):e62761. doi: 10.1371/journal.pone.0062761. Print 2013.