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Childhood Vasculitis

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pediatr. | doi: 10.3389/fped.2018.00341

S100A12 serum levels and PMN counts are elevated in childhood systemic vasculitides especially involving proteinase 3 specific anti-neutrophil cytoplasmic antibodies

 Kelly L. Brown1, 2,  Joanna M. Lubieniecka3, Giulia Armaroli4, Katharina Kessel4, Kirsten Gibson2, 5,  Jinko Graham3, Dongmeng Liu3,  Robert E. Hancock6, 7,  Colin Ross5, 7, Susanne Benseler8,  Raashid A. Luqmani9, David A. Cabral1, 2*,  Dirk Foell4* and  Christoph Kessel4
  • 1Department of Pediatrics, Faculty of Medicine, University of British Columbia, Canada
  • 2British Columbia Children's Hospital, Canada
  • 3Department of Statistics and Actuarial Science, Simon Fraser University, Canada
  • 4Abteilung für Pädiatrische Rheumatologie & Immunologie, Universitätsklinikum Münster, Germany
  • 5Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Canada
  • 6Department of Microbiology and Immunology, University of British Columbia, Canada
  • 7Centre for Microbial Diseases and Immunity Research, University of British Columbia, Canada
  • 8Department of Pediatrics, Alberta Children’s Hospital, Canada
  • 9Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Medical Sciences Division, University of Oxford, United Kingdom

Objectives. Chronic primary systemic vasculitidies (CPV) are a collection of rare diseases involving inflammation in blood vessels, often in multiple organs. CPV can affect adults and children and may be life- or organ-threatening. Treatments for adult CPV, although effective, have known severe potential toxicities; safety and efficacy of these drugs in pediatric patients is not fully understood. There is an unmet need for biologic measures to assess the level of disease activity and, in turn, inform treatment choices for stopping, starting or modifying therapy. This observational study determines if S100 calcium-binding protein A12 (S100A12) and common inflammatory indicators are sensitive markers of disease activity in children and adolescents with CPV that could be used to inform a minimal effective dose of therapy.
Methods. Clinical data and sera were collected from 56 participants with CPV at study visits from diagnosis to remission. Serum concentrations of S100A12, C-reactive protein (CRP) and hemoglobin (Hb) as well as whole blood cell counts and erythrocyte sedimentation rate (ESR) were measured. Disease activity was inferred by physician’s global assessment (PGA) and the pediatric vasculitis activity score (PVAS).
Results. Serum concentrations of standard markers of inflammation (ESR, CRP, Hb, absolute blood neutrophil count), and S100A12 track with clinically assessed disease activity. These measures – particularly neutrophil counts and sera concentrations of S100A12 – had the most significant correlation with clinical scores of disease activity in those children with vasculitis that is associated with anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3.
Conclusions. S100A12 and neutrophil counts should be considered in the assessment of disease activity in children with CPV particularly the most common forms of the disease that involve proteinase 3 ANCA.

Keywords: Chronic primary systemic vasculitis, Neutrophils (PMNs), S100A12, Proteinase 3 (PR3)-ANCA, Clinical scores

Received: 28 Jun 2018; Accepted: 22 Oct 2018.

Edited by:

Christian M. Hedrich, Institute of Translational Medicine, University of Liverpool, United Kingdom

Reviewed by:

Mindy S. Lo, Boston Children's Hospital, Harvard Medical School, United States
Henner Morbach, Department of Pediatrics, University Hospital Würzburg, Germany
Hermann Girschick, Vivantes Klinikum, Germany  

Copyright: © 2018 Brown, Lubieniecka, Armaroli, Kessel, Gibson, Graham, Liu, Hancock, Ross, Benseler, Luqmani, Cabral, Foell and Kessel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. David A. Cabral, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, V6T 1Z2, British Columbia, Canada,
Prof. Dirk Foell, Abteilung für Pädiatrische Rheumatologie & Immunologie, Universitätsklinikum Münster, Muenster, Germany,