S100A12 and S100A8/9 proteins are biomarkers of articular disease activity in Blau syndrome
Por:
Wang L, Rosé CD, Foley KP, Anton-Lopez J, Bader-Meunier B, Brissaud P, Chédeville G, Cimaz R, Fernández-Martín J, Guly C, Hachulla E, Harjacek M, Mackensen F, Merino R, Modesto C, Naranjo Hernández A, Pajot C, Ramanan AV, Thatayatikom A, Thomée C, Vastert S, Votta BJ, Bertin J and Wouters CH
Publicada:
1 jul 2018
Ahead of Print:
7 abr 2018
Resumen:
Objective. To identify biomarkers of articular and ocular disease activity in patients with Blau syndrome (BS)
Methods. Multiplex plasma protein arrays were performed in five BS patients and eight normal healthy volunteers (NHVs). Plasma S100A12 and S100A8/9 were subsequently measured by ELISA at baseline and 1-year follow-up in all patients from a prospective multicentre cohort study. CRP was measured using Meso Scale Discovery immunoassay. Active joint counts, standardization uveitis nomenclature for anterior uveitis cells and vitreous haze by Nussenblatt scale were the clinical parameters.
Results. Multiplex Luminex arrays identified S100A12 as the most significantly elevated protein in five selected BS vs eight NHVs and this was confirmed by ELISA on additional samples from the same five BS patients. In the patient cohort, S100A12 (n = 39) and S100A8/9 (n = 33) were significantly higher compared with NHVs (n = 44 for S100A12, n = 40 for S100A8/9) (P = 0.0000004 and P = 0.0003, respectively). Positive correlations between active joint counts and S100 levels were significant for S100A12 (P = 0.0008) and S100A8/9 (P = 0.015). CRP levels did not correlate with active joint count. Subgroup analysis showed significant association of S100 proteins with active arthritis (S100A12 P = 0.01, S100A8/9 P = 0.008). Active uveitis was not associated with increased S100 levels.
Conclusion. S100 proteins are biomarkers of articular disease activity in BS and potential outcome measures in future clinical trials. As secreted neutrophil and macrophage products, S100 proteins may reflect the burden of granulomatous tissue in BS.
Filiaciones:
Wang L:
Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA
Rosé CD:
Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Foley KP:
Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA
Anton-Lopez J:
Pediatric Rheumatology, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
Bader-Meunier B:
5 Service d'Immunologie- Hematologie et Rhumatologie Pediatrique, Hôpital Necker-Enfants Malades, Institut Imagine
Brissaud P:
Médecine Interne Rhumatologie, Hôpital Bichat-Claude Bernard, Paris, France
Chédeville G:
Division of Rheumatology, The Montreal Children's Hospital, Montreal, Quebec, Canada
Cimaz R:
AOU Meyer, Meyer Children's Hospital, Florence, Italy
Fernández-Martín J:
Internal Medicine, Hospital do Meixoeiro-Chuvi, Vigo, Pontevedra, Spain
Guly C:
Retina Unit, Bristol Eye Hospital, Bristol, UK
Hachulla E:
Service de Médecine Interne, Hôpital Claude Huriez, Lille, France
Harjacek M:
Rheumatology, Children's Hospital Srebrnjak, Zagreb, Croatia
Mackensen F:
Interdisciplinary Uveitis Center, Universitat Klinikum Heidelberg, Heidelberg, Germany
Merino R:
Unidad de Reumatologia Pediatrica, Hospital La Paz, Madrid
Modesto C:
Pediatric Rheumatology, Hospital Universitario Vall d'Hebron, Barcelona
Naranjo Hernández A:
Servicio de Rheumatologia, Hospital de Gran Canarias Dr Negrin, Las Palmas, Spain
Pajot C:
Service Urgences Service Médecine Interne-Rhumatologie, Hôpital des Enfants, Toulouse, France
Ramanan AV:
Department of Paediatric Rheumatology, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK
Thatayatikom A:
Division of Allergy/Immunology/Rheumatology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
Thomée C:
Service de Pédiatrie, Clinique Pédiatrique CHL, Luxembourg, Luxembourg
Vastert S:
Division of Pediatrics, Department of Pediatric Rheumatology and Immunology, UMC Utrecht, Utrecht, The Netherlands
Votta BJ:
Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA
Bertin J:
Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA
Wouters CH:
KU Leuven, Department of Microbiology and Immunology, Pediatric Immunology, University Hospitals Leuven, Pediatric Rheumatology, Leuven, Belgium
Green Submitted, Bronze
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