Journal Article

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

Goldbach-Mansky, Raphaela, Kuemmerle-Deschner, Jasmin B, Austermann, Judith, Wittkowski, Helmut, Lohse, Peter, Holzinger, Dirk, Gramlich, Katharina, Foell, Dirk, Jung, Thomas, Benseler, Susanne M, Roth, Johannes

2011

Overview

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.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group,Elsevier Limited
• Subject: Adolescent / Adult / Aged / Allergic diseases / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Antirheumatic Agents - therapeutic use / Arthritis / ATP-Binding Cassette Transporters - blood / Biological and medical sciences / Biomarkers / Biomarkers - blood / C-Reactive Protein - metabolism / Calgranulin B - blood / Child / Child, Preschool / Cryopyrin-Associated Periodic Syndromes - blood / Cryopyrin-Associated Periodic Syndromes - drug therapy / Cryopyrin-Associated Periodic Syndromes - immunology / Cytokines / Dermatology / Disease / Diseases of the osteoarticular system / Drug Monitoring - methods / Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue / Humans / Immunopathology / Inflammation / Inflammation Mediators - blood / Interleukin 1 Receptor Antagonist Protein - therapeutic use / Interleukin-1 - antagonists & inhibitors / Interleukin-1beta - antagonists & inhibitors / Malformations and congenital and or hereditary diseases involving bones. Joint deformations / Medical sciences / Middle Aged / Prospective Studies / Proteins / Recombinant Fusion Proteins - therapeutic use / Skin allergic diseases. Stinging insect allergies / Studies / Treatment Outcome / Young Adult