Calprotectin as a biomarker for rheumatoid arthritis: a systematic review.
OBJECTIVE
Calprotectin (myeloid-related protein 8/14), a heterodimeric complex of calcium-binding proteins, is expressed in granulocytes and monocytes. Calprotectin levels are high in synovial tissue, particularly in activated cells adjacent to the cartilage-pannus junction. This systematic review evaluates the use of calprotectin as an indicator of disease activity, therapeutic response, and prognosis in rheumatoid arthritis (RA).


METHODS
Medline, Scopus, and the Cochrane Library (1970-2013) were searched for studies containing original data from patients with RA in whom calprotectin levels were measured in plasma/serum and/or synovial fluid (SF). We included studies examining associations between calprotectin levels and clinical and laboratory assessments, disease progression, and therapeutic response. There were no restrictions for sample size, disease duration, or length of followup.


RESULTS
We evaluated 17 studies (1988-2013) with 1065 patients enrolled; 11 were cross-sectional and 8 had longitudinal designs with 2 studies reporting cross-sectional and longitudinal data. Systemic and SF levels of calprotectin were raised in RA. There was a wide range of levels and marked interstudy and intrastudy variability. Calprotectin levels were high in active disease and were particularly high in rheumatoid factor (RF)-positive patients. Levels fell with effective treatment. Longitudinal data showed that calprotectin was a significant and independent predictor of erosive progression and therapeutic responses, particularly in patients who received effective biological treatments.


CONCLUSIONS
SF calprotectin levels are high, suggesting there is substantial local production by inflamed synovium. Blood calprotectin levels, though highly variable, are elevated in active RA and fall with effective therapy. High baseline calprotectin levels predict future erosive damage.
From the Department of Rheumatology, King's College London School of Medicine, Weston Education Centre; Department of Rheumatology, University Hospital Lewisham; Department of Rheumatology, King's College Hospital, London, UK.M. Abildtrup, BSc (Hons), Medical Student, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre; G.H. Kingsley, MB ChB, PhD, FRCP, Professor of Clinical Rheumatology, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre, and Department of Rheumatology, University Hospital Lewisham; D.L. Scott, BSc, MD, FRCP, Professor of Clinical Rheumatology, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre, and Department of Rheumatology, King's College Hospital.
Mads
M
Abildtrup
From the Department of Rheumatology, King's College London School of Medicine, Weston Education Centre; Department of Rheumatology, University Hospital Lewisham; Department of Rheumatology, King's College Hospital, London, UK.M. Abildtrup, BSc (Hons), Medical Student, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre; G.H. Kingsley, MB ChB, PhD, FRCP, Professor of Clinical Rheumatology, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre, and Department of Rheumatology, University Hospital Lewisham; D.L. Scott, BSc, MD, FRCP, Professor of Clinical Rheumatology, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre, and Department of Rheumatology, King's College Hospital.
Gabrielle H
GH
Kingsley
From the Department of Rheumatology, King's College London School of Medicine, Weston Education Centre; Department of Rheumatology, University Hospital Lewisham; Department of Rheumatology, King's College Hospital, London, UK.M. Abildtrup, BSc (Hons), Medical Student, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre; G.H. Kingsley, MB ChB, PhD, FRCP, Professor of Clinical Rheumatology, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre, and Department of Rheumatology, University Hospital Lewisham; D.L. Scott, BSc, MD, FRCP, Professor of Clinical Rheumatology, Department of Rheumatology, King's College London School of Medicine, Weston Education Centre, and Department of Rheumatology, King's College Hospital. d.scott1@nhs.net david.l.scott@kcl.ac.uk.
David L
DL
Scott
D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D011379:Prognosis; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex
BIOLOGICAL MARKERS; CALGRANULIN A; CALGRANULIN B; DISEASE ACTIVITY; RHEUMATOID ARTHRITIS