Diagnostic Potential of Zymogen Granule Glycoprotein 2 Antibodies as Serologic Biomarkers in Chinese Patients With Crohn Disease

Abstract

The need for reliable biomarkers for distinguishing Crohn disease (CD) from ulcerative colitis (UC) is increasing. This study aimed at evaluating the diagnostic potential of anti-GP2 antibodies as a biomarker in Chinese patients with CD. In addition, a variety of autoantibodies, including anti-saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibodies (PANCA), anti-intestinal goblet cell autoantibodies (GAB), and anti-pancreatic autoantibodies (PAB), were evaluated.A total of 91 subjects were prospectively enrolled in this study, including 35 patients with CD, 35 patients with UC, 13 patients with non-IBD gastrointestinal diseases as disease controls (non-IBD DC), and 8 healthy controls (HC). The diagnosis of IBD was determined based on the Lennard-Jones criteria, and the clinical phenotypes of the IBD patients were determined based on the Montreal Classification.Anti-GP2 IgG antibodies were significantly elevated in patients with CD, compared with patients with UC (P = 0.0038), HC (P = 0.0055), and non-IBD DC (P = 0.0063). The prevalence of anti-GP2 IgG, anti-GP2 IgA and anti-GP2 IgA, or IgG antibodies in patients with CD was 40.0%, 37.1%, and 54.3%, respectively, which were higher than those in non-IBD DC (anti-GP2 IgG, 15.4%; anti-GP2 IgA, 7.7%; and anti-GP2 IgA or IgG, 23.1%) and those in patients with UC (anti-GP2 IgG, 11.4%; anti-GP2 IgA, 2.9%; and anti-GP2 IgA or IgG, 14.3%). For distinguishing CD from UC, the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratios (LR+) were 40%, 88.6%, 77.8%, and 3.51 for anti-GP2 IgG, 37.1%, 97.1%, 92.9%, and 13.0 for anti-GP2 IgA, and 54.3%, 85.3%, 79.2%, and 3.69 for anti-GP2 IgA or IgG. For CD diagnosis, the combination of anti-GP2 antibodies with ASCA IgA increased the sensitivity to 68.6% with moderate loss of specificity to 74.3%. Spearman's rank of order revealed a significantly positive correlation of anti-GP2 IgG with ileocolonic location of disease (L3) (P = 0.043) and a negative correlation of anti-GP2 IgA with biologic therapy (P = 0.012).Our findings suggest that anti-GP2 antibodies could serve as a biomarker for distinguishing patients with CD from patients with UC, and the combination of anti-GP2 antibodies with ASCA IgA may improve the predictive power.

Antibodies against glycoprotein 2 display diagnostic advantages over ASCA in distinguishing CD from intestinal tuberculosis and intestinal Behçet's disease

“…In this study, the prevalence of aGP2 was similar to our previous study on a small cohort of patients with IBD (49.7 vs. 54.3%), 21 was higher than those previously reported from Europe (20.7–36%). 30 , 31 , 32 , 33 As the pathogenesis of CD involves a combination of genetic, immunologic, and environmental risk factors, the relatively high prevalence of aGP2 in Chinese patients with CD might be due to the differences in those factors.…”

“…Serum aGP2 IgG and IgA were determined by ELISA (Generic Assays, Dahlewitz/Berlin, Germany), according to the manufacturer’s instructions. 21 The cutoff value for positivity was set to 15 U/ml for IgG aGP2 and 10 U/ml for IgA aGP2, as recommended by the manufacturer. Serum IgG ASCA and IgA ASCA were determined by ELISA (Inova Diagnostics, San Diego, USA).…”

“… 19 , 20 We have previously demonstrated that IgA/IgG aGP2 were present in 54.3% of Chinese patients with CD and just 14.3% with UC in small cohorts of patients with IBD (35 CD and CU patients, each), supporting the aforementioned diagnostic potential of aGP2. 21 However, the small sample size may have introduced analytic bias and, thus, a larger cohort study is badly needed. Furthermore, to our knowledge, no study has assessed the clinical relevance of aGP2 in distinguishing CD from ITB and intestinal BD.…”

Diagnostic value of the antiglycoprotein-2 antibody for Crohn’s disease: a PRISMA-compliant systematic review and meta-analysis

“…With regard to the geographic location of the studies, seven were carried out in Germany, 4 7 8 11 15 18 21 four in the UK 6 10 17 20 and one each in Serbia, the Netherlands, Hungary, the Czech Republic, Belgium and China. 9 12–14 16 19 Assessment using QUADAS indicated that the studies were of median to high quality, with positive results for at least 6/14 items.…”

Diagnostic Potential of Zymogen Granule Glycoprotein 2 Antibodies as Serologic Biomarkers in Chinese Patients With Crohn Disease

“…In the article “Diagnostic Potential of Zymogen Granule Glycoprotein 2 Antibodies as Serologic Biomarkers in Chinese Patients With Crohn Disease”, 1 which appeared in Volume 94, Issue 42 of Medicine , Dr. Yongzhe Li was not originally credited as a corresponding author in the article. The article has since been corrected online.…”