TY - JOUR

T1 - Alpha-1 antitrypsin and granulocyte colony-stimulating factor as serum biomarkers of disease severity in ulcerative colitis

AU - Soendergaard, Christoffer

AU - Nielsen, Ole Haagen

AU - Seidelin, Jakob Benedict

AU - Kvist, Peter Helding

AU - Bjerrum, Jacob Tveiten

PY - 2015/5

Y1 - 2015/5

N2 - BACKGROUND: Initial assessment of patients with ulcerative colitis (UC) is challenging and relies on apparent clinical symptoms and measurements of surrogate markers (e.g., C-reactive protein [CRP] or similar acute phase proteins). As CRP only reliably identifies patients with severe disease, novel biomarkers are currently needed for identification of patients with mild or moderate disease activity. Using a commercially available platform, we aimed at identifying serum biomarkers that are able to grade the disease severity.METHODS: Serum samples from 65 patients with UC with varying disease activity (Mayo score) and from 40 healthy controls were analyzed by multiplex enzyme-linked immunosorbent assay for 78 potential disease biomarkers. Using the statistical software SIMCA-P+ and GraphPad Prism, multivariate statistical analyses were conducted to identify a limited number of biomarkers to assess disease severity.RESULTS: Alpha-1 antitrypsin (AAT) differentiated between mild and moderate UC (area under the curve [AUC] = 0.79) with a sensitivity of 0.90 and a specificity of 0.70, thereby exceeding the predictive ability of CRP (AUC = 0.52). Combining alpha-1 antitrypsin and granulocyte colony-stimulating factor produced a predictive model with an AUC of 0.72 when differentiating mild and moderate UC, and an AUC of 0.96 when differentiating moderate and severe UC, the latter being as reliable as CRP.CONCLUSIONS: Alpha-1 antitrypsin is identified as a potential serum biomarker of mild-to-moderate disease activity in UC. With the ability to differentiate between mild, moderate, and severe stages of UC using a simple serum biomarker that is already commercially available, clinicians can initiate individualized treatment regimens at an earlier stage before endoscopic examinations are available.

AB - BACKGROUND: Initial assessment of patients with ulcerative colitis (UC) is challenging and relies on apparent clinical symptoms and measurements of surrogate markers (e.g., C-reactive protein [CRP] or similar acute phase proteins). As CRP only reliably identifies patients with severe disease, novel biomarkers are currently needed for identification of patients with mild or moderate disease activity. Using a commercially available platform, we aimed at identifying serum biomarkers that are able to grade the disease severity.METHODS: Serum samples from 65 patients with UC with varying disease activity (Mayo score) and from 40 healthy controls were analyzed by multiplex enzyme-linked immunosorbent assay for 78 potential disease biomarkers. Using the statistical software SIMCA-P+ and GraphPad Prism, multivariate statistical analyses were conducted to identify a limited number of biomarkers to assess disease severity.RESULTS: Alpha-1 antitrypsin (AAT) differentiated between mild and moderate UC (area under the curve [AUC] = 0.79) with a sensitivity of 0.90 and a specificity of 0.70, thereby exceeding the predictive ability of CRP (AUC = 0.52). Combining alpha-1 antitrypsin and granulocyte colony-stimulating factor produced a predictive model with an AUC of 0.72 when differentiating mild and moderate UC, and an AUC of 0.96 when differentiating moderate and severe UC, the latter being as reliable as CRP.CONCLUSIONS: Alpha-1 antitrypsin is identified as a potential serum biomarker of mild-to-moderate disease activity in UC. With the ability to differentiate between mild, moderate, and severe stages of UC using a simple serum biomarker that is already commercially available, clinicians can initiate individualized treatment regimens at an earlier stage before endoscopic examinations are available.

KW - Adult

KW - Aged

KW - Biomarkers

KW - C-Reactive Protein

KW - Case-Control Studies

KW - Colitis, Ulcerative

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Follow-Up Studies

KW - Granulocyte Colony-Stimulating Factor

KW - Humans

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Risk Factors

KW - Severity of Illness Index

KW - alpha 1-Antitrypsin

U2 - 10.1097/MIB.0000000000000348

DO - 10.1097/MIB.0000000000000348

M3 - Journal article

C2 - 25803506

VL - 21

SP - 1077

EP - 1088

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 5

ER -