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Ann Rheum Dis. 2011 Dec;70(12):2075-2081. doi: 10.1136/ard.2011.152496. Epub 2011 Sep 8.

MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes.

Author information

1
Department of General Paediatrics, University Children's Hospital Muenster, Muenster, Germany.
2
Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tuebingen, Tuebingen, Germany.
3
Institute of Immunology, University of Muenster, Muenster, Germany.
4
Interdisciplinary Centre for Clinical Research IZKF, University of Muenster, Muenster, Germany.
5
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA.
6
Department of Clinical Chemistry - Großhadern, University of Munich, Munich, Germany.
7
Novartis Pharma, Basel, Switzerland.
8
Division of Rheumatology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada.
#
Contributed equally

Abstract

OBJECTIVES:

To assess the sensitivity of the phagocyte-specific molecules myeloid-related protein (MRP) 8 and MRP14 (calprotectin) for monitoring disease activity during anti-interleukin (IL)-1 therapies in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular (CINCA) syndrome.

METHODS:

A total of 39 patients with CAPS, including 5 FCAS, 16 MWS and 18 CINCA syndrome, received anti-IL-1 therapy. All patients with CINCA and 12 with MWS were treated with IL-1Ra (anakinra), 14 patients with MWS with a monoclonal anti-IL-1β antibody (canakinumab) and patients with FCAS received IL-1 Trap (rilonacept). During serial clinical visits serum amyloid A, C-reactive protein, erythrocyte sedimentation rate and MRP8/14 serum levels were analysed.

RESULTS:

Untreated patients with CAPS had significantly elevated MRP8/14 values. In response to treatment there was a significant reduction of MRP8/14 levels in CINCA (2,830 (range 690 - 8,480) ng/ml to 670 ng/ml, p < 0.001) and MWS patients (anakinra-treated: 4,390 (1790 - 9780) ng/ml to 1,315 ng/ml (p = 0.003); canakinumab-treated: 3,000 (500 - 13060) ng/ml to 630 ng/ml (p=0.001)). However, in many patients with CAPS, MRP8/14 levels were still elevated compared with healthy individuals, reflecting residual disease activity. However, canakinumab-treated patients with CAPS showed normalised MRP8/14 levels, suggesting control of phagocyte activation.

CONCLUSIONS:

Monitoring of cellular systems involved in inflammatory cascades of the innate immunity was successfully applied to the IL-1-driven CAPS diseases. This is the first study illustrating different states of subclinical disease activity in all types of CAPS depending on the type of anti-IL-1 therapy. MRP8/14 is a sensitive biomarker for monitoring disease activity, status of inflammation and response to IL-1 blockade in patients with CAPS.

PMID:
21908452
PMCID:
PMC4174360
DOI:
10.1136/ard.2011.152496
[Indexed for MEDLINE]
Free PMC Article

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