Anti-GP2 IgA Research Articles

Loss of mucosal tolerance to glycoprotein 2 isoform 1 is a potential novel diagnostic biomarker for cholangiocarcinoma

BackgroundAnti-glycoprotein 2 (anti-GP2) IgA and antineutrophil-cytoplasmic antibodies to proteinase 3 (PR3-ANCA) have been reported as predictive markers of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC), but their prevalence in CCA patients without PSC remains unclear. MethodsThis study involved Asian discovery (n = 118) and European validation (n = 38) cohorts of CCA patients without PSC, alongside 49 Asian and 82 European pancreatic ductal adenocarcinoma (PDAC) patients, 21 with benign pancreatic neoplasms (BPN) and 45 with hepatocellular carcinoma (HCC), and 157 healthy controls (HC) from Asia and Europe. We analyzed the prevalence of PR3-ANCA, IgA and IgG against GP21 and GP24, and the CA19-9 levels. ResultsAnti-GP21 IgA was the most prevalent in both CCA cohorts (discovery: 55.1 %; validation: 42.1 %) and significantly higher than in other groups except PDAC (all p < 0.05). It demonstrated the best diagnostic performance in distinguishing CCA from disease controls and HC, outperforming tumor markers. No significant correlation was found between anti-GP21 IgA levels and CA19-9 levels. ConclusionOur findings show that anti-GP21 IgA revealing the loss of mucosal tolerance is a potential novel diagnostic biomarker for CCA.

Anti-glycoprotein 2 (anti-GP2) IgA and anti-neutrophil cytoplasmic antibodies to serine proteinase 3 (PR3-ANCA): antibodies to predict severe disease, poor survival and cholangiocarcinoma in primary sclerosing cholangitis.

SummaryBackgroundPrimary sclerosing cholangitis (PSC) is associated with progressive liver disease and cholangiocarcinoma. Although risk stratification is crucial for making clinical decisions, it is hindered by a scarcity of proven prognostic markers.AimsTo assess the value of novel anti‐glycoprotein 2 (anti‐GP2) and anti‐neutrophil cytoplasmic antibodies to serine proteinase 3 (PR3‐ANCA) in combination with PSC‐specific clinical and laboratory markers as predictors of quality of life, disease severity, and cholangiocarcinoma in two large, independent cohorts of PSC patientsMethodsDiscovery (338 Polish patients) and validation (178 German patients) cohorts with PSC were evaluated. Anti‐GP2 (isoforms 1/4) was detected by ELISAs and PR3‐ANCA by chemiluminescence immunoassay. Clinical and laboratory data were collected and analysed. The outcome was defined as liver transplantation‐free survival and occurrence of cholangiocarcinoma during follow‐up.ResultsIn the discovery group, anti‐GP21/4 IgA and PR3‐ANCA were associated with liver dysfunction, anti‐GP21/4 IgA with risk scores for PSC and anti‐GP24 IgA with cirrhosis. All cholangiocarcinoma patients were positive for PR3‐ANCA and/or anti‐GP24 IgA. The association between anti‐GP2 IgA and liver biochemistry, risk scores, cirrhosis, impaired survival, and cholangiocarcinoma was confirmed in the validation cohort. Cox proportional‐hazards regression indicated anti‐GP21 IgA as an independent variable of poor outcome in both study cohorts. Analysis of the combined data showed that anti‐GP24 IgA and PR3‐ANCA were independent predictors for cholangiocarcinoma, while anti‐GP21 IgA and PR3‐ANCA were indicators for poor survival.ConclusionsAnti‐GP2 and PR3‐ANCA are prognostic antibodies in PSC as they identify patients at risk of severe disease, poor survival and biliary cancer.

Antibodies Against Glycoprotein 2 Are Specific Biomarkers for Pediatric Crohn's Disease.

Serological markers can assist in accurate differentiation between Crohn's disease (CD) and ulcerative colitis (UC). One such marker is anti-glycoprotein 2 (anti-GP2) which was shown to be a specific marker for CD in adult patients. The aim of our study was to assess the utility of anti-GP2 and GP2 as biomarkers for pediatric CD, and determine whether they correlate with disease activity. Serum samples were tested by ELISA for anti-GP2 isoform 4 IgG and IgA, and also for GP2. Results were correlated with demographic and clinical data. The cohort consisted of 53 pediatric patients with CD, 42 with UC, and 53 controls. Levels of anti-GP2 were significantly increased in pediatric patients with CD in comparison with patients with UC, and control subjects, with high positive predictive value for both IgG and IgA (97.9% and 82.6%, respectively). While specificity of anti-GP2 IgG and IgA was very high (98.7% and 90.0%, respectively), sensitivity was low (42.0% and 35.5% for IgG and IgA, respectively). In CD, anti-GP2 correlated with disease activity, and decreased in treatment-naïve patients following successful induction therapy. A higher IgA anti-GP2 was also demonstrated in patients with ileo-colonic involvement, and was associated with a younger age. Finally, positive GP2 level was identified in only 1/211 serum samples. A positive anti-GP2 level is highly associated with CD, while a negative result does not exclude CD. Additional studies are required to determine whether these markers can be used in pediatric patients with CD for risk stratification.

Differential diagnosis of Crohn's disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae.

Glycoprotein 2 (GP2), the major autoantigen of Crohn's disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.

Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis

Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn’s disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4% (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9–99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05–21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target.

Autoantibodies Against Glycoprotein 2 Isoforms in Pediatric Patients with Inflammatory Bowel Disease

Anti-Glycoprotein 2 (GP2) antibodies are associated with a more complicated course of Crohn's disease (CD) in adults. Four different GP2 isoforms with different length and antibody-binding sites have been identified so far but not been explored in serological studies. We aimed to investigate the diagnostic utility of autoantibodies against all 4 isoforms of GP2 in an exclusively pediatric population for the first time. We included 278 children and adolescents with inflammatory bowel disease: 164 with CD, 114 with ulcerative colitis, 83 disease controls (acute gastrointestinal infection, nonspecific gastrointestinal functional disorders), and 219 healthy controls. Sera were tested for anti-GP2 antibodies using 4 different isoforms of GP2 for anti-Saccharomyces cerevisiae antibodies, antineutrophil cytoplasmic antibodies, and pancreatic antibodies. Anti-GP2 antibodies were significantly more prevalent in patients with CD than in ulcerative colitis and controls. We found a sensitivity of 38% (with a specificity of 95%) for anti-GP2 IgG against isoform 4 in CD. Anti-GP2 IgA against isoform 1 and anti-GP2 IgG against isoform 4 possessed the best diagnostic values for identification of CD. For the differentiation of CD from ulcerative colitis anti-GP2 IgG against isoforms 3 and 4 proved to be most accurate markers. Anti-GP2 antibodies were associated with a more complicated disease behavior and bowel surgery in CD. In a subgroup of patients with CD, anti-GP2 IgG against isoform 4 proved to be a relatively stable marker over time independent of disease activity. Anti-GP2 antibodies against different isoforms are specific markers for CD and for different phenotypes in pediatric inflammatory bowel disease.

Serologic Anti-GP2 Antibodies Are Associated with Genetic Polymorphisms, Fibrostenosis, and Need for Surgical Resection in Crohn's Disease.

The presentation of Crohn's disease (CD) is heterogeneous and often leads to serious complications and need for surgery. We tested serum anti-zymogen granule glycoprotein 2 (GP2) antibodies, including its novel isoform alpha, for association with genetic variants, diagnosis, disease stratification, and prediction of CD courses in a combined cross-sectional and cohort study. Serum samples of 303 CD, 108 ulcerative colitis, 72 other inflammatory gastrointestinal diseases, and 206 controls without predominant gastrointestinal diseases controls (HC) were tested for the presence of Anti-GP2 and Anti-Saccharomyces cervisiae (ASCA) by enzyme-linked immunosorbent assay. Genetic analysis was performed using the Illumina Immunochip. GP2 IgA and IgG had the highest discriminatory capability for CD versus ulcerative colitis and CD versus inflammatory gastrointestinal diseases. We identified an association of GP2 IgA and IgG each with 5 distinct single-nucleotide polymorphisms. Levels of anti-GP2 IgG were moderately associated with ileal disease location. Interestingly, both, anti-GP2 IgA and IgG were exclusively associated with the occurrence of stenosis and need for surgery, independently of disease location, but not with fistulizing CD, early disease onset or disease activity. ASCA IgG and IgA were qualitatively and quantitatively linked to CD, CD complications, and need for surgery. Increased levels of ASCA IgG and IgA and positivity for ASCA IgG, but neither levels nor positivity for GP2 IgG or IgA were predictive of the earlier occurrence of complications or surgery. Anti-GP2 antibodies may aid as a tool for diagnosis and differentiation of CD and could indicate a more complicated CD course.

Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis

ObjectivePancreatic autoantibodies (PABs), comprising antibodies against glycoprotein 2 (anti-GP2), are typically associated with complicated phenotypes in Crohn's disease, but have also been observed with variable frequencies in patients with UC....

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

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.

Serum Anti-GP2 Antibody Isoforms 1 and 4 Are associated With Crohnʼs Disease of the Pouch in Patients With Ileal-Pouch Anal Anastomosis (IPAA)

Introduction: IPAA is the standard therapy for ulcerative colitis (UC) patients requiring colectomy. Inflammatory and non-inflammatory complications of the ileal pouch are common. Serologic antimicrobial antibodies, such as pANCA, cBir1 or anti-glycan antibodies have been linked to pouchitis in IPAA subjects, but limited accuracy restricts their clinical use. Zymogen granule glycoprotein 2 (GP2) is the major autoantigen of CD-specific pancreatic autoantibodies. We tested two novel serologic anti-GP2 isoforms for association with pouch disorders in a cross-sectional analysis in IPAA patients. Methods: 157 serum samples of 143 consecutive and eligible pouch patients (mean age 43.6 +/- 13.4 years, 45.5% female) were obtained from the pouch clinic of a tertiary academic center. Serial samples were available for 13 subjects. Pouch disorders were diagnosed based on clinical, endoscopic, histologic and radiographic criteria. Presence of Anti-GP2 IgG and IgA Isoforms 1 & 4 was tested in serum samples using enzyme-linked immunosorbent assay (ELISA). Clinical data was recorded prospectively (pre-operative diagnosis, indication for colectomy, pouch type, pouch complications). Analysis was performed using Kruskal-Wallis, Pearson's chi square, Wilcoxon signed rank or Fisher's exact tests. Results: Median interval from construction of IPAA to sample procurement was 7.1 years (25th percentile 2.1; 75th percentile 13.2). 89.5% of participants had a J-pouch. Upon sample procurement, patient phenotypes included: normal pouch n=66, irritable pouch syndrome n=5, acute pouchitis n=17, refractory pouchitis n=24, CD of the pouch n=16, cuffitis n=30, other n=22. Presence of Anti-GP2 IgG Isoform 1 (p < 0.001) & 4 (p < 0.001) and Anti-GP2 IgA Isoform 1 (p=0.022) & 4 (p < 0.001) was associated with CD of the pouch. Presence of Anti-GP2 IgG Isoform 4 was linked to cuffitis (p=0.006). No marker was associated with pre-operative CD. Median interval time between serum procurement in IPAA subjects with serial samples was 3 months. There was no significant change in serum levels of Anti-GP2 antibodies over time. Conclusion: This study demonstrates a link between the two isoforms of Anti-GP2 antibodies with CD of the pouch in IPAA patients. Anti-GP2 was not associated with a pre-operative diagnosis of CD and anti-GP2 levels were stable over time. Serologic anti-GP2 antibodies could aid in diagnosis of CD of the pouch after IPAA.

Loss and Gain of Tolerance to Pancreatic Glycoprotein 2 in Celiac Disease.

BackgroundAutoantibodies against pancreatic secretory-granule membrane glycoprotein 2 (GP2) have been demonstrated in patients with Crohn’s disease but recently also with celiac disease (CD). Both entities are characterized by intestinal barrier impairment with increased gut permeability. Pathophysiological hallmark of CD is a permanent loss of tolerance to alimentary gliadin and a transient loss of tolerance to the autoantigen human tissue transglutaminase (tTG). Therefore, we explored the behavior of loss of tolerance to GP2 reported in CD.MethodsWe assessed prevalences and levels of autoantibodies against GP2, CD-specific antibodies to endomysial antigens and tTG as well as Crohn’s disease-specific anti-Saccharomyces cerevisiae antibodies in sera of 174 patients with active CD, 84 patients under gluten-free diet (GFD) and 129 controls. Furthermore, we looked for an association between anti-GP2 antibody positivity and degree of mucosal damage in CD.ResultsWe found significantly elevated anti-GP2 IgA positivity in active CD patients (19.5%) compared to CD patients under GFD (0.0%) and controls (5.4%, p < 0.001, respectively). Anti-GP2 IgA levels correlated significantly with CD-specific antibodies (p < 0.001). Anti-GP2 autoantibody positivity disappeared under GFD similarly to CD-specific autoantibodies against tTG and endomysial antigens. For the first time, IgA antibody levels to GP2 are demonstrated to be associated with degree of villous atrophy according to Marsh classification.ConclusionsAnti-GP2 IgA seems to be associated with disease activity in a distinct subgroup of patients with CD. The observed loss of tolerance to GP2 in a subset of patients with CD is transient and disappears under GFD.

Anti-Outer membrane protein C and anti-glycoprotein 2 antibodies in inflammatory bowel disease and their association with complicated forms of Crohn's disease.

BackgroundPrecise diagnostics of inflammatory bowel disease (IBD) and identification of potentially more aggressive phenotypes of Crohn’s disease (CD) is urgently needed. The aim of our prospective study was to assess the relationship between serum anti-OmpC IgA (Outer membrane protein C), anti-GP2 (anti-glycoprotein 2) IgG and anti-GP2 IgA antibodies with IBD and their association with complicated forms of CD.MethodsThe study included 86 patients with CD, 25 patients with UC and 45 controls, blood donors. In CD group, 24/86 (28%) had B1 phenotype, 20/86 (23%) B2, 13/86 (15%) B3 and 29/86 (34%) B2 + B3. L1 involvement was present in 13/86 (15%), L2 in 13/86 (15%), L3 in 60/86 (70%). Serum anti-OmpC IgA, anti-GP2 IgG and IgA antibodies were investigated by means of ELISA. The data obtained were tested statistically by means of descriptive statistics, non-paired t-test, Mann-Whitney rank sum test, Spearman rank order correlation and Pearson product moment correlation using SigmaStat software.ResultsAnti-OmpC IgA were noted to be significantly higher in CD (median 32.6, inter-quartile range (IQR) 18.9-60.7) compared to the controls (median 18.3, IQR 11.1-23.1), p < 0.001. Anti-GP2 IgG were significantly higher in CD (median 13.9, IQR 8.6-25.6) compared to the controls (median 8.0, IQR 4.7-10.8), p < 0.001. Anti-GP2 IgA were significantly higher in CD (median 20.1, IQR 9.1-40.4) compared to the controls (median 9.8, IQR 5.6-16.9), p < 0.001. Significant difference was found in anti-OmpC IgA between UC (median 26.2, IQR 20.2-36.4) and the controls (median 18.3, IQR 11.1-23.1), p < 0.001. In CD anti-OmpC IgA were significantly higher in B2 compared to B1: p = 0.041 and in B2 + B3 compared to B1: p = 0.036. Anti-GP2 IgA were significantly higher in B2 + B3 compared to B1: p = 0.009 and in B3 compared to B1: p = 0.029. In CD there was a significant difference in anti-OmpC IgA between patients with surgery and without surgery, p = 0.005.ConclusionsWe have confirmed association between anti-OmpC IgA and IBD (CD and UC) and an association between anti-GP2 (IgG and IgA) and CD. Patients with complicated forms of CD have significantly higher levels of anti-OmpC IgA and anti-GP2 IgA.

Evidence of Crohn's disease-related anti-glycoprotein 2 antibodies in patients with celiac disease.

Autoantibodies to exocrine-pancreatic glycoprotein 2 (anti-GP2) are Crohn's disease (CD) markers. However, CD-specific antibodies have also been found in celiac-disease (CeD) patients, in which type 1 diabetes-specific autoantibodies against endocrine pancreatic targets can be present. We investigated whether anti-GP2 are also present in CeD, a disease like CD which is also characterised by intestinal mucosal inflammation with barrier impairment. Antibodies against GP2, tissue transglutaminase (tTG), deamidated gliadin (dGD), glutamic decarboxylase (GAD), and islet antigen-2 (IA2) were tested in sera from 73 CD patients, 90 blood donors (BD), and 79 (58 de novo) CeD patients (2 consecutive sera were available from 40 patients). IgA and/or IgG anti-GP2 were found in 15/79 (19.0%) CeD patients on at least one occasion, in 25/73 (34.2%) CD patients, and in 4/90 (4.4%) BD (CeD vs. CD, p=0.042; BD vs. CeD and CD, p<0.001, respectively). Amongst the 58 de novo CeD patients, anti-GP2 IgA and/or IgG were present in 11 (19.0%). Anti-GP2 IgA was significantly less prevalent in CeD compared with CD (p=0.004). Anti-GP2 IgA and IgG in CD patients demonstrated a significantly higher median level compared to patients with CeD (p<0.001, p=0.008, respectively). IgA anti-GP2 levels correlated significantly with IgA anti-tTG and anti-dGD levels in CeD Spearman's coefficient of rank correlation (ρ)=0.42, confidence interval (CI): 0.26-0.56, p<0.001; ρ=0.54, CI 0.39-0.65, p<0.001, respectively. The presence of anti-GP2 in CeD patients supports the notion that loss of tolerance to GP2 can probably be a manifestation of an autoinflammatory process in this intestinal disorder.

AB0985 Anti-GP2 Antibodies Presense in Patients with Rheumatic Diseases

BackgroundAutoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. The role of impaired intestinal barrier function on...

Mo1248 Weekend Hospitalizations Are Associated With Increased Post-Operative Complications Following Urgent Surgery for Ulcerative Colitis

Background: Crohǹs disease (CD) often leads to serious complications, such as fistulae and strictures as well as need for surgery. Early and prolonged immunosuppressive therapy has the potential to alter the natural history of CD. Several serum markers have been tested for the stratification of CD, but their use in clinical practice is still limited. Recently zymogen granule glycoprotein 2 (GP2)was identified as themajor autoantigen of CD-specific pancreatic autoantibodies. Aims: We tested serologic anti-GP2 antibodies for their association with complications and surgery, disease location, disease activity and age at disease onset in patients with CD in a cross-sectional analysis. Methods: Serum samples from 303 CD patients of a tertiary university hospital (mean age 36.1 years, 52.8% female) were tested for the presence of Anti-GP2 IgA and Anti-GP2 IgG by ELISA. Clinical data on disease location, age at disease onset, clinical disease activity, serum CRP, complications (strictures and fistulae) and surgery were available in a prospectively maintained database. Analysis was performed using Wilcoxon rank sum test and logistic regression analysis. Reported odds ratios (ORs) correspond to 10 unit (U) increase in marker levels. Results: After a median follow-up time from diagnosis of 104.6 [interquartile range (IQR) 58.1,168.1] months 77.6% of the CD patients had a complication (49.2% fistulae, 58.4% stenosis), 72.3% underwent surgery and 85.5% had ileal disease involvement. At time of sample procurement 36.5% had clinically active disease and 51.6% had elevated CRP. Levels of anti-GP2 IgG were linked to complicated CD (p=0.002, area under the curve (AUC) 0.62) and ileal disease location (p=0.004, AUC 0.64). Interestingly, both, anti-GP2 IgA and IgG were associated with the occurrence of stenosis and need for surgery (p ,0.001 p=0.003, AUC 0.62 0.64), but not with fistulizing CD, early disease onset, clinically active disease or elevated CRP. After correction for early disease onset and ileal involvement anti-GP2 IgG levels remained significantly linked to stenosis (OR for 10 U increase in GP2 IgG: 1.07 (95% confidence interval (CI): 1.01, 1.1)) and need for surgery (OR for 10 U increase in GP2 IgG: 1.1 (95% CI: 1.01, 1.2)). If patients had both, strictures and fistulae, the association of anti-GP2 IgG with stricturing CD remained significant after correction for the presence of fistulas (OR for 10 U increase in GP2 IgG: 1.07 (95% CI 1.02, 1.1)). Conclusions: Specific levels of anti-GP2 antibodies are independently associated with stricturing CD and need for surgical intervention. Ongoing studies evaluate anti-GP2 levels for their predictive capabilities, the stability of these markers over time and the combination with genetic markers to assess their use in clinical practice.

Mo1247 Serologic Anti-GP2 Antibodies Are Associated With Strictures and Need for Surgical Resection in Crohn's Disease

Background: Crohǹs disease (CD) often leads to serious complications, such as fistulae and strictures as well as need for surgery. Early and prolonged immunosuppressive therapy has the potential to alter the natural history of CD. Several serum markers have been tested for the stratification of CD, but their use in clinical practice is still limited. Recently zymogen granule glycoprotein 2 (GP2)was identified as themajor autoantigen of CD-specific pancreatic autoantibodies. Aims: We tested serologic anti-GP2 antibodies for their association with complications and surgery, disease location, disease activity and age at disease onset in patients with CD in a cross-sectional analysis. Methods: Serum samples from 303 CD patients of a tertiary university hospital (mean age 36.1 years, 52.8% female) were tested for the presence of Anti-GP2 IgA and Anti-GP2 IgG by ELISA. Clinical data on disease location, age at disease onset, clinical disease activity, serum CRP, complications (strictures and fistulae) and surgery were available in a prospectively maintained database. Analysis was performed using Wilcoxon rank sum test and logistic regression analysis. Reported odds ratios (ORs) correspond to 10 unit (U) increase in marker levels. Results: After a median follow-up time from diagnosis of 104.6 [interquartile range (IQR) 58.1,168.1] months 77.6% of the CD patients had a complication (49.2% fistulae, 58.4% stenosis), 72.3% underwent surgery and 85.5% had ileal disease involvement. At time of sample procurement 36.5% had clinically active disease and 51.6% had elevated CRP. Levels of anti-GP2 IgG were linked to complicated CD (p=0.002, area under the curve (AUC) 0.62) and ileal disease location (p=0.004, AUC 0.64). Interestingly, both, anti-GP2 IgA and IgG were associated with the occurrence of stenosis and need for surgery (p ,0.001 p=0.003, AUC 0.62 0.64), but not with fistulizing CD, early disease onset, clinically active disease or elevated CRP. After correction for early disease onset and ileal involvement anti-GP2 IgG levels remained significantly linked to stenosis (OR for 10 U increase in GP2 IgG: 1.07 (95% confidence interval (CI): 1.01, 1.1)) and need for surgery (OR for 10 U increase in GP2 IgG: 1.1 (95% CI: 1.01, 1.2)). If patients had both, strictures and fistulae, the association of anti-GP2 IgG with stricturing CD remained significant after correction for the presence of fistulas (OR for 10 U increase in GP2 IgG: 1.07 (95% CI 1.02, 1.1)). Conclusions: Specific levels of anti-GP2 antibodies are independently associated with stricturing CD and need for surgical intervention. Ongoing studies evaluate anti-GP2 levels for their predictive capabilities, the stability of these markers over time and the combination with genetic markers to assess their use in clinical practice.

Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and behaviour in younger patients with Crohn’s disease

BackgroundGlycoprotein 2 (GP2) was discovered as the major autoantigen of Crohn’s disease (CD)-specific pancreatic autoantibodies (PAB). We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes.MethodsAnti-GP2 and anti-Saccharomyces cerevisiae (ASCA) IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF) in 271 sera, 169 with CD and 102 with ulcerative colitis (UC). As healthy controls 160 adult blood donors and 65 children were included.ResultsAnti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2%) than in UC (9/102, 8.9%) patients and in controls (9/225, 4%) (p < 0.001 respectively). ASCA IgG and/or IgA were present in 60/169 (35.5%) in CD and in 7/102 (6.9%) in UC patients (p < 0.001). CD patients with ileocolonic location (L3) showed a significantly higher prevalence of anti-GP2 and ASCA IgA and/or IgG (40/113 and 48/113, respectively; p < 0.05 for both comparisons), whereas CD patients with colonic location (L2) revealed a significantly diminished prevalence for these autoantibody specificities (2/32 and 5/32, respectively, p < 0.05 for both). Anti-GP2 IgG were significantly more prevalent in CD patients with stricturing behaviour (B2) and perianal disease (7/11, p < 0.02) and less prevalent in those with penetrating behaviour (B3) and perianal disease (4/31, p < 0.05). The occurrence of anti-GP2 IgA and/or IgG was significantly more prevalent in CD patients with age at diagnosis of ≤16 years (16/31, p < 0.009). Prevalence of one or more anti-GP2 or ASCA IgA and/or IgG was significantly higher in L3, B2, and A1 and lower in L2 (68/113, 27/41, 23/31, 6/32; p < 0.04, respectively).ConclusionsAnti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.

Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, are new markers in Crohn's disease

Background Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by reactivity against microbial and self antigens. Zymogen granule glycoprotein 2 (GP2) was identified as the major autoantigen of CD-specific pancreatic autoantibodies (PAB). Methods Human GP2 was expressed in the Spodoptera frugiperda 9 (Sf9) cell line using the baculovirus system, purified by Ni-chelate chromatography, and used as antigen for anti-GP2 IgA and IgG assessment by enzyme-linked immunosorbent assays (ELISA). Antibodies to mannan of Saccharomyces cerevisiae (ASCA), PAB, and anti-GP2 were investigated in sera of 178 CD patients, 100 ulcerative colitis (UC) patients, and 162 blood donors (BD). Results Anti-GP2 IgG and IgA were found in 48/72 (66.7%) and 23/72 (31.9%) PAB positive and 5/106 (4.7%) and 1/106 (0.9%) PAB negative CD patients (p < 0.0001), respectively. CD patients displayed significantly higher reactivity to GP2 than UC patients and BD (p < 0.0001), respectively. Occurrence of anti-GP2 antibodies correlated with PAB reactivity (Spearmen's rho = 0.493, p < 0.00001). There was a significant relationship between the occurrence of ASCA IgG and anti-GP2 IgG (p = 0.0307). Conclusions Anti-GP2 IgG and IgA constitute novel CD specific autoantibodies, the quantification of which could improve the serological diagnosis of IBD.