Critical: Spin, pour, freeze serum within 4 hours of collection. Two 0.3mL serum in clear aliq
External Client Shipping and Handling
Specimen Preparation, Storage/Transport Temperature:
Keep sample as ambient whole blood prior to processing. Separate serum from cells within 4 hours of collection. Freeze two 0.3mL serum aliquots immediately at -20°C or lower. Separated serum samples must be sent with enough dry ice to maintain a frozen state until received in our lab.
The lab operates Mon-Fri, 8:00am to 5:00pm (EST). Testing is not performed and samples cannot be received on weekends/certain holidays. First Overnight shipping is strongly recommended. Please call/fax (513-636-4685/513-636-3861) the tracking number so we may better track your specimen.
The calcium-binding proteins S100A8 (alias: MRP8), S100A9 (alias: MRP14) and S100A12 (aliases: Calgranulin C, EN-RAGE) are typically secreted during activation of neutrophils and monocytes. S100A8/A9 form a complex (alias: calprotectin) that can serve as an endogenous TLR agonist and trigger TLR4 signaling pathways [1] leading to production of proinflammatory cytokines including IL1-β. S100A12 can also activate human monocytes via Toll-like receptor 4 [2,3].
High levels of S100A8/A9 and S100A12 are characteristic of active systemic juvenile idiopathic arthritis (sJIA) and may distinguish sJIA from other febrile illnesses, including systemic infection, various forms of leukemia, and Kawasaki disease [4,5]. S100A8/9 serum concentrations correlate closely in response to drug treatment and disease activity and therefore might be an additional measurement for monitoring anti-inflammatory treatment of individual patients with sJIA. During clinically inactive disease, S100A8/9 serum concentrations are reported to be one of the first predictive biomarkers indicating subclinical disease activity [6], and low S100A8/A9 levels indicate that it is relatively unlikely that subclinical disease activity is present at the time the test is performed [7]. Highly elevated S100 proteins are also a feature that may be shared with other auto-inflammatory syndromes such as Familial Mediterranean Fever (FMF) and cryopyrin-associated periodic syndromes CAPS [8], and may be elevated in other diseases.
1. Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C, Roth J: Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat.Med. 2007, 13:1042-1049. 2. Foell D, Wittkowski H, Vogl T, Roth J: S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J.Leukoc.Biol. 2007, 81:28-37. 3 Kessel C, Holzinger D, Foell D: Phagocyte-derived S100 proteins in autoinflammation: putative role in pathogenesis and usefulness as biomarkers. Clin.Immunol. 2013, 147:229-241. 4. Wittkowski H, Hirono K, Ichida F, Vogl T, Ye F, Yanlin X, Saito K, Uese K, Miyawaki T, Viemann D, Roth J, Foell D: Acute Kawasaki disease is associated with reverse regulation of soluble receptor for advance glycation end products and its proinflammatory ligand S100A12. Arthritis Rheum. 2007, 56:4174-4181.
5. Frosch M, Ahlmann M, Vogl T, Wittkowski H, Wulffraat N, Foell D, Roth J: The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1beta form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum.2009, 60:883-891. 6. Holzinger D, Frosch M, Kastrup A, Prince FH, Otten MH, Van Suijlekom-Smit LW, ten CR, Hoppenreijs EP, Hansmann S, Moncrieffe H, Ursu S, Wedderburn LR, Roth J, Foell D, Wittkowski H: The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis.Ann.Rheum.Dis. 2012, 71:974-980.
7. Foell, D. et al. Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA 2010; 303: 1266–1273.
Critical: Spin, pour, freeze serum within 4 hours of collection. Two 0.3mL serum in clear aliq
External Client Shipping and Handling
Specimen Preparation, Storage/Transport Temperature:
Keep sample as ambient whole blood prior to processing. Separate serum from cells within 4 hours of collection. Freeze two 0.3mL serum aliquots immediately at -20°C or lower. Separated serum samples must be sent with enough dry ice to maintain a frozen state until received in our lab.
The lab operates Mon-Fri, 8:00am to 5:00pm (EST). Testing is not performed and samples cannot be received on weekends/certain holidays. First Overnight shipping is strongly recommended. Please call/fax (513-636-4685/513-636-3861) the tracking number so we may better track your specimen.
The calcium-binding proteins S100A8 (alias: MRP8), S100A9 (alias: MRP14) and S100A12 (aliases: Calgranulin C, EN-RAGE) are typically secreted during activation of neutrophils and monocytes. S100A8/A9 form a complex (alias: calprotectin) that can serve as an endogenous TLR agonist and trigger TLR4 signaling pathways [1] leading to production of proinflammatory cytokines including IL1-β. S100A12 can also activate human monocytes via Toll-like receptor 4 [2,3].
High levels of S100A8/A9 and S100A12 are characteristic of active systemic juvenile idiopathic arthritis (sJIA) and may distinguish sJIA from other febrile illnesses, including systemic infection, various forms of leukemia, and Kawasaki disease [4,5]. S100A8/9 serum concentrations correlate closely in response to drug treatment and disease activity and therefore might be an additional measurement for monitoring anti-inflammatory treatment of individual patients with sJIA. During clinically inactive disease, S100A8/9 serum concentrations are reported to be one of the first predictive biomarkers indicating subclinical disease activity [6], and low S100A8/A9 levels indicate that it is relatively unlikely that subclinical disease activity is present at the time the test is performed [7]. Highly elevated S100 proteins are also a feature that may be shared with other auto-inflammatory syndromes such as Familial Mediterranean Fever (FMF) and cryopyrin-associated periodic syndromes CAPS [8], and may be elevated in other diseases.
1. Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C, Roth J: Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat.Med. 2007, 13:1042-1049. 2. Foell D, Wittkowski H, Vogl T, Roth J: S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J.Leukoc.Biol. 2007, 81:28-37. 3 Kessel C, Holzinger D, Foell D: Phagocyte-derived S100 proteins in autoinflammation: putative role in pathogenesis and usefulness as biomarkers. Clin.Immunol. 2013, 147:229-241. 4. Wittkowski H, Hirono K, Ichida F, Vogl T, Ye F, Yanlin X, Saito K, Uese K, Miyawaki T, Viemann D, Roth J, Foell D: Acute Kawasaki disease is associated with reverse regulation of soluble receptor for advance glycation end products and its proinflammatory ligand S100A12. Arthritis Rheum. 2007, 56:4174-4181.
5. Frosch M, Ahlmann M, Vogl T, Wittkowski H, Wulffraat N, Foell D, Roth J: The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1beta form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum.2009, 60:883-891. 6. Holzinger D, Frosch M, Kastrup A, Prince FH, Otten MH, Van Suijlekom-Smit LW, ten CR, Hoppenreijs EP, Hansmann S, Moncrieffe H, Ursu S, Wedderburn LR, Roth J, Foell D, Wittkowski H: The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis.Ann.Rheum.Dis. 2012, 71:974-980.
7. Foell, D. et al. Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA 2010; 303: 1266–1273.
