An Overview of The 10 Biomarkers in the PROMETHEUS® IBS Diagnostic
Interleukin 1β (IL-1β)ª
IL-1β is a proinflammatory cytokine that plays a central role in inflammatory diseases such as IBD.1 Animal studies suggest that as an inhibitor of acetylcholine-induced intestinal contraction in colonic mucosa, long-term IL-1β exposure induces a myogenic inhibitory action in intestinal muscle motility.1,2 Also, glucocorticoids released during stress suppress inflammation and have a significant down-regulatory effect on IL-1β, which is central to the cellular immune response.3
Growth-Related Oncogene α (GRO-α)
GRO-α is a chemokine that can cause chemotactic migration and activation of neutrophils.4 GRO-α expression in epithelial cells and cells of the immune system is associated with angiogenesis, a key process in inflammation, wound repair, and tumor growth.5,6 Its expression may be involved in tissue injury in IBD patients through recruitment and cellular activation of neutrophils.4 In animal studies, it has been associated with hyperalgesia,7 a common component of IBS.
Brain-Derived Neurotrophic Factor (BDNF)
BDNF is a nerve growth factor thought to be a major regulator of neuronal transmission.8,9 Within the viscera, BDNF enhances neuronal responsiveness, increases neurotransmitter density, and facilitates release of neurotransmitters from the enteric nervous system.8 These effects suggest that BDNF plays an important stimulant role in long-term regulation of gastrointestinal motility.8
Anti-Saccharomyces Cerevisiae Antibody Immunoglobulin A (ASCA IgA)
ASCA IgA is an antibody that recognizes the carbohydrate moiety of the cell wall of yeast10; its presence may reflect a generalized loss of immunotolerance or may represent cross-reactivity to an unidentified pathogen. ASCA is frequently found in Crohn’s disease patients.11
Antibody Against CBir1 (anti-CBir1)b
Anti-CBir1 is an antibody against bacterial flagellin.12 Bacterial flagellins have the potential to activate the secretion of epithelial chemokines and increase gene expression in the intestinal epithelia.13 Cells of the gut mucosa recognize bacterial flagellin, which is known to activate innate immunity.12
Antihuman Tissue Transglutaminase (tTG)
tTG is a tissue-repair enzyme14 and the major autoantigen in celiac disease.15 It belongs to a family of cell types that act by joining together proteins to promote wound healing and bone growth.4,16 tTG also acts on gliadin, which cross-reacts with bowel tissue that leads to an inflammatory reaction and decreased intestinal absorption in celiac patients.16,17 Anti-tTG testing, particularly if a human recombinant antigen is used, will likely lead to a more precise diagnosis of celiac disease.15
TNF-Like Weak Inducer of Apoptosis (TWEAK)
TWEAK is a cytokine that controls diverse cellular activities such as proliferation, migration, differentiation, apoptosis, and angiogenesis.18-20 In the event of acute injury, TWEAK also coordinates responses required for facilitating tissue repair.20 TWEAK levels are down-regulated in autoimmune pathologies.21
Antineutrophil Cytoplasmic Antibody (ANCA)
ANCAs are autoantibodies that target antigens present in neutrophils.22 Antibodies against neutrophils are detected in a number of inflammatory and autoimmune disorders,22 and ANCAs have been identified in the serum of 50% to 80% of ulcerative colitis patients.23 A relationship has also been established between the expression of serum antibodies to ANCA and the presence of Crohn’s disease.10
Tissue Inhibitor of Metalloproteinase-1 (TIMP-1)
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TIMP-1 is an inhibitor of matrix metalloproteinases (MMPs) that break down extracellular matrix proteins involved in wound healing, angiogenesis, and tumor-cell metastasis.24 The activity of these proteins is controlled by tissue inhibitors of metalloproteinase (TIMPs),25 particularly TIMP-1.26 In the gut, altered TIMP activity can result in tissue destruction, intestinal barrier function impairment, bacterial influx, and excessive immune response.27
Neutrophil Gelatinase-Associated Lipocalin (NGAL)
NGAL belongs to the lipocalin family of proteins. Lipocalins are a diverse family of small secreted proteins that generally bind small hydrophobic ligands, soluble extracellular macromolecules, and possibly specific cell-surface receptors.28 NGAL appears to modulate various cellular responses, such as proliferation, apoptosis, and differentiation.29 In the viscera, it is involved in a range of functions including molecule transportation and gastrointestinal mucosal regeneration.30 NGAL facilitates mucosal regeneration by promoting cell migration in the GI tract.30
a patent pending
b patented
View References 1
Association of 10 biomarkers to four critical pathophysiologic pathways believed to be dysregulated in IBS
Ability of the digestive system to move its contents along its tract.
Brain-Gut Axis
The important relationship between events that affect the function of the central nervous system (brain) and the influence these factors have on the function of the intestines via the specialized enteric nervous system of the intestine.
Neuronal Regulation
A mechanism for synaptic pruning during brain maturation.
Intestinal Permeability or Absorption
The ability of the intestine to take in or release its contents.
Visceral Hypersensitivity or Hyperalgesia
Increased sensation or pain in the gut.
Immune Function
The production and action of cells that fight disease or infection.
Autoimmune
The process of making antibodies against the body’s own tissues.
Inflammation
Response to injury or foreign invasion designed to protect the body; the symptoms are heat, redness, swelling, and pain.
Cell proliferation/tissue repair
An increase in the number of cells as a result of cell growth and cell division or the repair of such cells.
View References 2
