Cytokines have emerged as molecules of importance in the regulation of many immunologic processes in the cell. The ability to accurately measure quantitative and qualitative differences in cytokine production is becoming increasingly important to the understanding of normal and pathological processes.
About Graft versus Host Disease (GvHD)
Graft versus host disease (GvHD) is one of the major causes of morbidity and mortality associated with allogeneic stem cell transplants. GvHD occurs in 30 – 50% of HLA-matched sibling transplants and 60 – 90% of matched unrelated donors.1,2 GvHD often manifests in the skin, liver and/or gastrointestinal (GI) tract, and is caused by immune dysregulation that is initiated when allogeneic donor T cells recognize host tissues as foreign. GvHD may be either acute or chronic. Acute GvHD (aGvHD), which typically occurs in the first 3 months post-transplant, has an incidence of 19 – 66% and carries a poor prognosis if the disease is severe. Chronic GvHD (cGvHD) occurs 3 months to > 1 year post-transplant and has a pathophysiology that is distinct from aGvHD, although poorly understood. The overall incidence of cGvHD is 40 – 50%.3
Pre-transplant conditioning regimens may damage host tissue, which in turn leads to inflammatory cytokine release (TNF-α, INF-γ, IL-1 and IL-6) directly from damaged tissues. The inflammatory cytokines stimulate antigen presenting cells which present host antigens to donor lymphocytes. In response, donor T cells proliferate, differentiate and undergo activation. Once donor T cells are activated, pro-inflammatory cytokines are produced in large quantities resulting in additional inflammation, recruitment of neutrophils to the site, and ultimately severe tissue damage. Administration of immunosuppressive agents are commonly used to treat cases of GvHD.
In skin, aGvHD frequently manifests as a maculopapular skin rash due to cellular/tissue damage. In the GI tract, aGvHD which frequently manifests as nausea, vomiting, anorexia, secretory diarrhea and in severe cases abdominal pain and at times hemorrhage, is caused by cellular damage to the mucosal epithelial barrier of the small intestines. The occurrence of aGvHD in the liver results in elevated bilirubin levels, indicative of liver damage.
Diagnosis of aGvHD has traditionally been based on the clinical presentation and ruling out other etiologies through differential diagnosis. In some cases biopsies of the liver, skin or GI tract are performed. In recent years, measurement of specific biomarkers, some of which are cytokines, has been shown to provide improved aGvHD diagnostic and prognostic approaches while utilizing in vitro methods and readily available samples such as serum. Recent research has identified several key biomarkers useful for aGvHD diagnosis and prognosis.4Procedure
Multiplex array format with Meso Scale Discovery (MSD®) Sector Imager 2400. MSD Cytokine assays measure from one to ten cytokines in a 96 well MULTI-SPOT plate. The assay employs a sandwich immunoassay format. MSD technology uses electrochemiluminescence detection; a CCD camera allows for the quantification of light emitted from each spot in each well. MSD software generates a standard curve to determine sample cytokine concentrations. This test has not been cleared or approved for diagnostic use by the U.S. Food and Drug Administration.
3-5 business days from receipt of specimen
|Specimen Type||Order Code||CPT Code||NY Approved||Volume||Assay Range||Special Instructions|
1 mL (min. 100 uL)
2.3 - 2300 pg/mL
The reference range for a healthy population is less than 10.4 pg/mL. However it should be noted that these ranges are obtained from a limited population of apparently healthy adults and are not diagnostic thresholds.
Specimens are approved for testing in New York only when indicated in the Specimen Information field above.
The CPT codes provided are based on Viracor Eurofins' interpretation of the American Medical Association's Current Procedural Terminology (CPT) codes and are provided for general informational purposes only. CPT coding is the sole responsibility of the billing party. Questions regarding coding should be addressed to your local Medicare carrier. Viracor Eurofins assumes no responsibility for billing errors due to reliance on the CPT codes illustrated in this material.References
1 Ball LM, Egeler RM, EBMT Paediatric Working Party. Acute GvHD: pathogenesis and classification. Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S58-64.
2 Deeg HJ, Henslee-Downey PJ. Management of acute graft-versus-host disease. Bone Marrow Transplant. 1990 Jul;6(1):1-8.
3 Atkinson K. Chronic graft-versus-host disease. Bone Marrow Transplant. 1990 Feb;5(2):69-82.
4 Paczesny S, Krijanovski OI, Bruan TM, et al. A biomarker panel for acute graft-versus-host disease. Blood. 2009 Jan 8;113(2):273-8.
Chung KF Cytokines: An overview in New Drugs for Asthma, Allergy and COPD, Prog Respir Res. 2001, vol 31: 242-246.
MSD 96-Well MULTI-ARRAY and MULTI-SPOT Human Cytokine Assays: Ultra Sensitive Kit package insert. Meso Scale Discovery
Bienvenu JA et al. Cytokine assays in human sera and tissues. Toxicology 1998; 129: 55-61.
Debad, J.D., Glezer, E.N., Wohlstadfer, J.N., Sigal, G.B. (2004) Clinical and Biological Applications of ECL. In Electrogenerated Chemiluminescence, ed. A.J. Bard. Marcel Dekker, New York, pp. 43-78.