Diagnostic utility of serological biomarkers in patients with Crohn's disease: A case-control study

Abstract

The aim of this study was to examine the expression of serological markers in patients with inflammatory bowel disease in China, and determine the diagnostic utility of serological markers, individually and in combination, for the diagnosis and differential diagnosis of Crohn's disease (CD).Serum samples were obtained from 160 participants in Eastern China. Among the participants, 98 were diagnosed with CD, 33 had ulcerative colitis (UC), and 29 were healthy controls (HC). The serum samples were tested for the presence of antibodies against outer membrane porin C (anti-OmpC), Pseudomonas fluorescens bacterial sequence I2 (anti-I2), anti-laminarin (anti-L), anti-chitin (anti-C), anti-chitobioside carbohydrate antibody (ACCA), anti-laminaribioside carbohydrate antibody (ALCA), anti-mannobioside carbohydrate antibody (AMCA), and anti-Saccharomyces cerevisiae antibody (ASCA) by indirect enzyme-linked immunosorbent assay (ELISA).Individually, anti-C, anti-L, ASCA-IgG, and ALCA lacked diagnostic value in the differentiation of CD. ASCA-IgA remained the most accurate marker for the diagnosis of CD, with an area under the curve (AUC) of 0.77; however, its sensitivity and specificity were both lower than 75%. Among the combinations of the 5 markers with significant diagnosing ability for CD, combinations with any 2 of the 3 markers, ASCA IgA, AMCA, and ACCA positive, provided the best accuracy in the diagnosis and differential diagnosis of CD (sensitivity and specificity both above 75%) and had the highest Youden index.Serological antibodies, when considered in combination, have remarkable value in the diagnosis and differential diagnosis of CD. Especially, the combination of any 2 of the 3 markers, ASCA-IgA, AMCA, ACCA positive, appears to be optimal.

Figure 1

Serum levels of anti-Saccharomyces cerevisiae antibody (ASCA) IgA and IgG, anti-laminaribioside carbohydrate antibody (ALCA), anti-mannobioside carbohydrate antibody (AMCA), anti-chitobioside carbohydrate antibody (ACCA), anti-chitin (anti-C), anti-laminarin (anti-L), antibody against outer membrane porin C (anti-OmpC), antibody against the Pseudomonas fluorescens bacterial sequence I₂ (anti-I₂) in patients with Crohn's disease and the control. The box plots indicated the average of the serum levels and the whiskers above the box indicated the variance. ACCA = anti-chitobioside carbohydrate antibody, anti-C = anti-chitin, anti-L = anti-laminarin, ALCA = anti-laminaribioside carbohydrate antibody, AMCA = anti-mannobioside carbohydrate antibody, ASCA = anti-Saccharomyces cerevisiae antibody.

Figure 2

Receiver operating characteristic (ROC) curves of anti-Saccharomyces cerevisiae antibody (ASCA) IgA and IgG, anti-laminaribioside^^ carbohydrate antibody (ALCA), anti-mannobioside carbohydrate antibody (AMCA), anti-chitobioside carbohydrate antibody (ACCA), antibody against outer membrane porin C (anti-OmpC), antibody against the Pseudomonas fluorescens bacterial sequence I₂ (anti-I₂) for discriminating Crohn's disease and the control. Under the reference line, the area under the curve (AUC) =0.5. AUC < .6, low diagnostic accuracy. ACCA = anti-chitobioside carbohydrate antibody, anti-C = anti-chitin, ALCA = anti-laminaribioside carbohydrate antibody, AMCA = anti-mannobioside carbohydrate antibody, ASCA = anti-Saccharomyces cerevisiae antibody, ROC = receiver operating characteristic.

Figure 3

Receiver operating characteristic curves for the different combinations of anti-Saccharomyces cerevisiae antibody (ASCA) IgA with any one of the remaining 4 markers. Under the reference line, the area under the curve (AUC) =.5. AUC < .6, low diagnostic accuracy. ASCA = anti-Saccharomyces cerevisiae antibody, AUC = area under the curve.

Figure 4

Receiver operating characteristic curves for the different combinations of anti-Saccharomyces cerevisiae antibody (ASCA) IgA with any 2 of the remaining 4 markers. Under the reference line, the area under the curve (AUC) =0.5. AUC < 0.6, low diagnostic accuracy. ASCA = anti-Saccharomyces cerevisiae antibody, AUC = area under the curve.

Figure 5

Receiver operating characteristic curves for the different combinations of anti-Saccharomyces cerevisiae antibody (ASCA) IgA with any 3 of the remaining 4 markers. Under the reference line, the area under the curve (AUC) =0.5. AUC < 0.6, low diagnostic accuracy. ASCA = anti-Saccharomyces cerevisiae antibody, AUC = area under the curve.

Figure 6

Receiver operating characteristic curves for the different combinations of anti-Saccharomyces cerevisiae antibody (ASCA) IgA with the remaining 4 markers. Under the reference line, the area under the curve (AUC) =0.5. AUC < 0.6, low diagnostic accuracy. ASCA = anti-Saccharomyces cerevisiae antibody, AUC = area under the curve.