title: Alpha-1 antitrypsin and granulocyte colony-stimulating factor as serum biomarkers of disease severity in ulcerative colitis.
abstract: 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.
authors: *Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark; and †Department of Histology, Novo Nordisk A/S, Maaloev, Denmark.
authors: Christoffer
authors: C
authors: Soendergaard
authors: Ole Haagen
authors: OH
authors: Nielsen
authors: Jakob Benedict
authors: JB
authors: Seidelin
authors: Peter Helding
authors: PH
authors: Kvist
authors: Jacob Tveiten
authors: JT
authors: Bjerrum
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index; D000515:alpha 1-Antitrypsin / Q000097:blood*
chemical_list: D015415:Biomarkers; D000515:alpha 1-Antitrypsin; D016179:Granulocyte Colony-Stimulating Factor; D002097:C-Reactive Protein