Saccharomyces Cerevisiae Antibodies Research Articles

Prevalence of Anti- Saccharomyces Cerevisiae Antibodies (ASCA) in Patients With Irritable Bowel Syndrome (IBS). A Case-control Study.

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects patients' quality. Recent research has shown variations in the mycobiome of individuals with IBS, particularly involving Saccharomyces cerevisiae , and its association with dysbiosis and visceral hypersensitivity. However, the role of Anti-Saccharomyces cerevisiae antibodies (ASCA) in IBS remains unclear, despite their significance as markers of disease severity in inflammatory bowel disease. This study aimed to investigate the role of ASCA in Mexican IBS patients compared with healthy controls (HCs) and determine whether these antibodies could help differentiate between IBS patients and healthy individuals. Serum samples from 400 IBS patients and 400 HC were analyzed. ASCA IgG levels were measured using enzyme-linked immunosorbent assay (ELISA). The IBS patients were further categorized into subtypes: constipation predominant (IBS-C), diarrhea predominant (IBS-D), and mixed (IBS-M). Among the participants, 66 IBS patients (16.5%) and 63 HC (15.75%) tested positive for ASCA IgG. No significant difference was observed in ASCA IgG levels between the 2 groups ( P value: 0.8451). The prevalence of ASCA IgG positivity was 14.5% in IBS-C, 17.8% in IBS-D, and 15.9% in IBS-M. Surprisingly, a high prevalence of ASCA IgG was found in the HC group in Mexico. Furthermore, there was no significant difference in ASCA IgG levels between IBS patients and controls. These findings suggest that ASCA is not useful as a discriminatory biomarker for distinguishing IBS patients from healthy individuals and cannot serve as a surrogate marker for visceral hypersensitivity.

Women with type 1 diabetes exhibit a progressive increase in gut Saccharomyces cerevisiae in pregnancy associated with evidence of gut inflammation

AimsStudies of the gut microbiome have focused on its bacterial composition. We aimed to characterize the gut fungal microbiome (mycobiome) across pregnancy in women with and without type 1 diabetes. MethodsFaecal samples (n = 162) were collected from 70 pregnant women (45 with and 25 without type 1 diabetes) across all trimesters. Fungi were analysed by internal transcribed spacer 1 amplicon sequencing. Markers of intestinal inflammation (faecal calprotectin) and intestinal epithelial integrity (serum intestinal fatty acid binding protein; I-FABP), and serum antibodies to Saccharomyces cerevisiae (ASCA) were measured. ResultsWomen with type 1 diabetes had decreased fungal alpha diversity by the third trimester, associated with an increased abundance of Saccharomyces cerevisiae that was inversely related to the abundance of the anti-inflammatory butyrate-producing bacterium Faecalibacterium prausnitzii. Women with type 1 diabetes had higher concentrations of calprotectin, I-FABP and ASCA. ConclusionsWomen with type 1 diabetes exhibit a shift in the gut mycobiome across pregnancy associated with evidence of gut inflammation and impaired intestinal barrier function. The relevance of these findings to the higher rate of pregnancy complications in type 1 diabetes warrants further study.

S2453 Not Just Your Average Ulcer

Introduction: Behcet’s disease is a multisystem inflammatory disease and vasculitis of unknown etiology described by a Turkish dermatologist, Hulusi Behçet, in 1937. About 10-15% of patients can have gastrointestinal (GI) involvement, which makes it challenging to differentiate from Crohn’s disease. Here we describe the case of a patient diagnosed with both Behcet’s and Crohn’s disease. Case description/methods: A 25-year-old male from the county of Georgia presented with a history of perirectal abscess and fistula for 6 months. He reported worsening abdominal pain, bloody diarrhea, and drainage at the site of the fistula. On examination, he was found to have oral ulcers (Fig. 1A), genital ulcers (Fig. 1B), an anorectal fistula with purulent discharge (Fig. 1C), acneiform skin lesions on the back, joint pains with stiffness, and photosensitivity. He had been diagnosed with Behcet’s disease by rheumatology about 5 months back after meeting the Revised International Criteria for Behcet’s disease. He was started on colchicine, which controlled his extra-intestinal symptoms; however, he continued to have perirectal pustular drainage and bloody diarrhea. CT enterography showed an anorectal fistula, and he was referred to GI for further management. Fecal calprotectin was elevated to 165 ug/mg and the Saccharomyces cerevisiae IgG was positive (31.6). He underwent upper endoscopy and colonoscopy, which showed a duodenal bulb ulcer and multiple clean-based longitudinal ulcers (2-5 mm) in the descending colon (Fig. 1D), sigmoid colon (Fig. 1E) and rectum (Fig. 1F). Biopsies showed focal active ileitis, along with focal active colitis in the right colon, descending colon, and rectum. Behcet’s disease can have GI involvement with discrete round ulcers in the ileo-cecal region. Fistula and abscess formation are extremely rare (<1% chance). With the presence of a positive Saccharomyces cerevisiae antibody, an anorectal fistula, and active colitis in the right and left colon, it was concluded that our patient likely had both Behcet’s disease and Crohn’s disease. He was started on Humira, which completely resolved his symptoms and healed the anorectal fistula.Figure 1.: Physical examination and colonoscopy findings. Discussion: Intestinal Behcet’s and Crohn’s disease mimic each other, and it is hard to differentiate the two from each other. Round fewer ulcers and the absence of a cobblestone appearance are hallmarks of intestinal Behcet’s disease. Fistulizing Behcet’s disease is extremely rare and, if seen, should prompt the physician to search for an alternative diagnosis.

S2397 First Reported Case of Kikuchi-Fujimoto Disease in a Crohn’s Disease Patient

Introduction: Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare entity, mostly associated with autoimmune conditions such as SLE. It is benign, focal, self-limited, and despite abundant literature, its pathogenesis remains unknown. We report a unique case of KFD in a patient with coexisting Crohn’s disease. Case description/methods: A 23-year-old female with no medical history was evaluated for Iron deficiency anemia and anorexia. She underwent a colonoscopy which revealed normal colonic mucosa, however, an ulcerated and congested terminal ileum was seen. Biopsies were significant for acute cryptitis and granuloma. Serology was positive for anti–Saccharomyces cerevisiae antibody and fecal calprotectin was elevated. She was initially started on oral corticosteroids and later transitioned to azathioprine and Adalimumab, with a good response. 7 months later, she was planned for a repeat colonoscopy to check for endoscopic healing, however, at her pre-procedure COVID testing, she was noted to have rubbery painless LAD of the right neck. The procedure was postponed and she was immediately asked to discontinue her medications. She was referred to an oncologist. A CT chest was unremarkable and an excisional biopsy of the largest of the lymph node revealed necrotizing lymphadenitis, favoring KFD. Infectious workup was negative. Over the next 2 months, her LAD spontaneously resolved without the need for medications. A repeat colonoscopy was aborted due to poor prep. A follow-up MRE revealed long segment mid and distal Crohn's ileitis, and fecal calprotectin remained elevated. She was started on oral budesonide with plans to restart biological therapy after repeating a colonoscopy. Discussion: KFD may rarely involve the terminal ileum, potentially masquerading as Crohn’s disease. Our patient, however, had histological findings pathognomic for Crohn’s and her ileitis did not resolve with the resolution of LAD. Lymphoma remains a feared adverse outcome of both immunomodulators and Anti-TNF medications, thus necessitating their cessation upon signs of LAD. However negative EBV testing, an unrevealing chest CT, and a benign histological diagnosis of KFD may allow our patient to safely resume these medications to treat her Crohn's.Figure 1.: Excisional Lymph node biopsy specimen demonstrating necrotizing histiocytic lymphadenitis. No infectious organisms were identified (Negative PAS, Warthin-Starry stain, Tuberculosis, HSV 1/2 and EBV immunohistochemistry).

S2837 An Uncommon Diagnosis Presenting as Acute Blood Loss Anemia

INTRODUCTION: Cryptogenic Multifocal Ulcerous Stenosing Enteritis (CMUSE) is a rare disease that is difficult to diagnose because of the nonspecific clinical manifestations and vague radiological findings across multiple diagnostic modalities. This abstract aims to present a case of CMUSE, re-iterate how its presentation can mimic other common GI conditions, and emphasize the importance of its consideration when the common GI conditions do not align with a patient's presentation. CASE DESCRIPTION/METHODS: 78 year old male presents with two episodes of hematochezia. Pt denied prior history of anemia or melena and was not on oral anticoagulation. He completed a colonoscopy which revealed pan diverticulosis and internal hemorrhoids. He continued to have intermittent hematochezia with significant anemia. A pill cam was then completed and showed distal small bowel with active bleeding from unclear etiology. A distal small bowel stricture was noted to be present, and for this reason, the pill cam was unable to pass. CT enterography was then recommended; this did not reveal a colonic stricture as was seen on the pill cam study, but rather, it revealed a 1cm enhancing nodule in the distal small bowel. Surgery was consulted for small bowel laparoscopy with plan for resection of the nodule to obtain pathology. Two small bowel tumors were observed in the distal ileum approximately 10cm apart in addition to a jejunal diverticulum with thickened tissue. Pathology reported non-specific shallow ulceration confined to the mucosa and submucosa and no identifiable granulomas. Working differential diagnoses at that time included: Crohn’s Disease, CMUSE, and Drug Induced Ulceration with Stenosis. Immunological work revealed negative C-ANCA, P-ANCA, Saccharomyces Cerevisiae Antibodies: IgG 4.5, IgA 5.2 (Relative Ranges 0–24.9). After negative antibody titers, the working diagnosis in this patient is CMUSE. DISCUSSION: Although this patient did not present with an ileus as many patients with CMUSE do, the anemia 2/2 GI bleeding, ulcerations and capsule retention in the distal small bowel are consistent with the diagnosis. Tao et al reported in 2019 that the most effective form of treatment is immunotherapy and surgery, the reported patient receiving the latter. However, the recurrence rate is high, and some patients become steroid dependent. Increasing awareness of this condition can contribute to identification of the optimal treatment of this rare condition in an effort to improve the lives of those affected.Figure 1.: One centimeter enhancing nodule in the distal small bowel noted on CT enterography.Figure 2.: Active bleeding in distal small bowel noted on pill cam study.

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa

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The purpose of study is to establish features of autoimmune reaction of children with Crohn's disease. The sampling included 62 patients aged from 2 to 17 years with diagnosis of Crohn's disease. The evaluation was carried out concerning concentration in blood serum of immunoglobulins IgA, IgM, IgG, IgЕ, antibodies to Saccharomyces cerevisiae (ASCA) classes IgA, IgG и IgЕ, antibodies to Candida albicans classes IgA, IgM, IgG и IgЕ, anti-neutrophilic cytoplasmic antibodies (ANCA) to myeloperoxidase (MPO), to proteinase 3 (PR3), anti-nuclear antibodies (ANA), antibodies to DNAds, DNAss (to double-helical and single-stranded DNA), antibodies to antigens of small and large intestines, pancreas, circulating immune complexes. The hyperimmunoglobulinemia was diagnosed in 47 (75.8%) out of 62 patients with Crohn's disease. The increased level of IgM in blood was detected in 29 patients (46.8%). The hyperimmunoglobulinemia У was established in 19 (30.6%) out of 62 children. The hypoimmunoglobulinemia was detected in 22 (35.5%) of patients and in 17 (77.3%) out of them the disimmunoglobulinemia type IV (isolated decreasing of concentration of IgA). The evaluation of rate of occurrence of specifc antibodies in blood serum demonstrated that in patients most frequently was detected presence of specifc IgE to Saccharomyces cerevisiae (70.9%). The increased level of ASCA (IgA, IgG) was detected in 22 (35.5%) patients. The concentration of antibodies to DNAds, DNAss in blood exceeded standard value in 4.8% and 16.1% patients correspondingly. The increased level of circulating immune complex was established in 20 (32.3%) patients. The concentration of ANA corresponded to standard values in all 62 (100%) patients. The evaluation of results of correlation analysis established a strong positive correlation of concentration in blood of antibodies to antigens of small and large intestines; average positive correlation of level of antibodies to antigens of small intestine and IgM, ANCA PR3, ASCA IgE, antibodies to Candida albicans classes IgM, IgG, IgE, antibodies to antigens of pancreas; average degree of positive correlation between concentration of antibodies to antigens of large intestine and IgA, IgM, circulating immune complex, ANCA PR3, DNAss, ASCA IgE, antibodies to antigens of pancreas; strong positive correlation between concentrations of IgA to Candida albicans and ANA. The detection of auto-to antibodies Saccharomyces cerevisiae, Candida albicans, ANCA, antigens of small and large intestines, pancreas and expressed degree of correlation of many indices of autoimmune reaction indicate to intensity of immune pathological process under Crohn's disease. Under Crohn's disease, the formation of antibodies to ASCA is a prognostically unfavorable sign. The immune diagnostic under Crohn's disease is necessary for evaluating severity of course of disease, differential diagnostic, establishment of prognosis and selection of individual immune correcting therapy.

353 Anti–Saccharomyces cerevisiae antibodies (ASCA) are biomarkers of moderate-to-severe hidradenitis suppurativa (HS), but not of severe plaque psoriasis: Results from a prospective, multicenter study

353 Anti–Saccharomyces cerevisiae antibodies (ASCA) are biomarkers of moderate-to-severe hidradenitis suppurativa (HS), but not of severe plaque psoriasis: Results from a prospective, multicenter study

Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease: 2-year clinical experience.

Antibodies to saccharomyces cerevisiae (ASCA), antibodies to perinuclear anti-neutrophil cytoplasmic (pANCA), pancreatic autoantibodies (PAB) and antibodies against intestinal goblet cells (GAB) are important in diagnosing Crohn's disease (CD) and ulcerative colitis (UC). However, little is known about their diagnostic value in real clinical practice in China. This retrospective study aimed to present our 2-year clinical experience with those biomarkers in diagnosis of CD and UC. A total of 140 patients with UC, 128 patients with CD, and 224 patients with intestinal associated diseases as disease controls were included. Serum ASCA were determined by ELISA. Serum pANCA, GAB, and PAB were tested by indirect immunofluorescent assay. Retrospective review of laboratory results and clinical information was performed. ASCA and ASCA+/pANCA- showed poor abilities in differentiating CD from UC, CD from intestinal Behçet's disease (BD), or CD from intestinal tuberculosis (ITB). In contrast, PAB exhibited good capacities in differentiating CD from UC, CD from intestinal BD, and CD from ITB. IgG pANCA demonstrated a high sensitivity and specificity in differentiating UC from CD. pANCA+/ASCA- or pANCA+/PAB- displayed a high sensitivity and specificity in differentiating UC from CD. GAB showed poor potential in differentiating UC from CD. PAB were positively correlated with early disease onset, ileocolonic disease, and perianal disease in CD patients. Our data suggest that pANCA and PAB are helpful in diagnosis of UC and CD, respectively, while ASCA and GAB were not. Our findings indicate a clear need for additional biomarkers for diagnosis of CD in China.

Auto-antibodies in patients with inflammatory bowel disease unclassified.

Inflammatory bowel disease unclassified (IBDU) is considered to be an aberrant immune response with loss of tolerance to many antigens. This paper tries to address whether there is any value to test for auto-antibodies in such patients. 60 patients with inflammatory bowel disease unclassified participated in the study. Auto-antibodies to nuclear antigen, intestinal goblet cell, exocrine part of pancreatic acinar cells, perinuclear antineutrophil cytoplasmic, cytoplasmic antineutrophil cytoplasmic and Saccharomyces cerevisiae were tested and compared to 20 ulcerative colitis (UC) patients and 30 healthy controls matched for age and sex. There was a significant difference (p=0.000) between patients and control group in anti-exocrine part of pancreatic acinar cells, perinuclear antineutrophil cytoplasmic and Saccharomyces cerevisiae auto-antibodies. There was also a significant difference between IBDU and UC patients in the auto-antibodies directed against intestinal goblet cells, (p=0.000) exocrine part of pancreas (p=0.000) and anti Saccharomyces cerevisiae antibody (p=0.000). Due to the autoimmune nature of indeterminate colitis, involvement of some antigens from gastrointestinal tract or the bile system in the initiation of this disease is likely.

Serum Anti-Saccharomyces Cerevisiae Antibodies in Greek Patients with Behcet's Disease

We tested 59 Greek patients with Behcet's Disease (BD) for serum anti-Saccharomyces cerevisiae antibodies. No increase of these antibodies was detected in the cases compared to 55 healthy unrelated blood donors from the same population. This finding is in contrast with the correlation between Saccharomyces cerevisiae antibodies and BD as reported in other populations. It seems that environmental factors may contribute to disease expression in different populations, producing different effects according to the individual's genetic predisposition. Saccharomyces cerevisiae antibodies do not seem to be of any significance in the Greek population.

Crohn's Disease of the Ileal Pouch 16 Years After Proctocolectomy for Ulcerative Colitis

This 34-year-old man is referred to our institution for possible Crohn’s disease. He was diagnosed with ulcerative colitis at age 6 years. His disease was eventually refractory to medical therapy, and he underwent a 2-stage proctocolectomy with ileal J-pouch to anal sewn anastomosis and temporary ileostomy at age 17 years. After takedown of the ileostomy his bowel function stabilized, with 6 stools daily with abdominal cramping pain, fecal urgency, and smallvolume nocturnal fecal incontinence. He had minimal improvement in symptoms with alternating courses of metronidazole and ciprofloxacin. Pouch endoscopy at age 33 showed multiple pouch ulcers. The anti–Saccharomyces cerevisiae antibodies (ASCA) and the perinuclear antineutrophil cytoplasmic antibody (p-ANCA) were negative. He had temporary relief of symptoms with courses of prednisone 20 mg daily, with recurrence after discontinuation. He developed postprandial abdominal cramping pain, abdominal distention, and nausea that gradually worsened and was not relieved by prednisone 40 mg daily. He did not improve with azathioprine. He developed severe bronchospasm during initial infusion of infliximab, and it was discontinued. At the time of referral he appears about 5 kg below ideal weight. The pouch-anal anastomosis is normally patent. Pouch endoscopy reveals multiple deep ulcers in the pouch and ulcers and narrowing of the lumen in the pre-pouch ileum (Figure 1), and biopsies show nonspecific ileitis. A contrast pouchogram shows a fistula from the pouch to the proximal ileum and a stricture in the pre-pouch ileum, with dilatation of the more proximal ileum (Figure 2). He undergoes abdominal exploration; there is a tight stricture at the junction of the pre-pouch ileum and the proximal pouch, and the distal 20 cm of the pre-pouch ileum is markedly dilated. There is a tight stricture in the midpouch, and the proximal pouch is very large. The pouch is disconnected from the anus and reduced in size. Two strictureplasties are performed, and the pouch is reanastomosed to the anus, and a temporary diverting ileostomy is placed. Azathioprine and adalimumab are started. The temporary ileostomy is taken down after 6 months. At 2 years after his most recent surgery, he reports about 6 stools daily, with rare nocturnal fecal incontinence and daily mild abdominal cramping pain. He continues on azathioprine and adalimumab. Pouch endoscopy shows scattered superficial ulcers in the pouch, with a normal pre-pouch ileum. Laboratory studies including C-reactive protein are normal (Figure 3). Case Discussion Despite advances in diagnostic methods during the past 30 years, there remains uncertainty in differentiating ulcerative colitis from Crohn’s disease of the colon in about 10% of patients. This subset of colitis has been termed indeterminate colitis, and more recently the term inflammatory bowel disease unclassified (IBDU) has been proposed. In a European multicenter study of 97 patients with indeterminate colitis as defined by clinical, radiographic, endoscopic, and histologic criteria, 48.5% were negative for both ASCA and p-ANCA. After a mean follow-up of 9.9 years, only 14.9% of those patients with IBDU who were ASCA and p-ANCA negative developed Crohn’s disease (as did the patient in this case discussion) or ulcerative colitis compared with 48% of patients with a positive serology, with ASCA/p-ANCA as a predictor of Crohn’s disease and ASCA/p-ANCA as a predictor of ulcerative colitis. This patient most likely had Crohn’s disease from the onset, with recurrence in the ileal pouch and pre-pouch ileum after colectomy and pouch anal anastomosis. It was not possible to determine by endoscopy whether inflammatory changes limited to the pouch were due to idiopathic pouchitis or to Crohn’s disease. Pouch biopsies occasionally show noncaseating granulomas, indicative of Crohn’s disease, but this is the exception, and no granulomas were found on biopsies in this patient. There was a pouch to ileal fistula as well as ulceration and stenosis in the pre-pouch ileum; these are hallmarks of Crohn’s disease and are not features of idiopathic pouchitis. The patient had minimal improvement with metronidazole and ciprofloxacin, and this is atypical for patients with idiopathic pouchitis, because a majority responds favorably to antibiotics. Failure to achieve an acceptable symptomatic improvement with antibiotics raises the possibility of another etiology for the pouch inflammation, such as Crohn’s disease as in the case of this patient, or obstruction for a

Presence of Anti-Microbial Antibodies in Liver Cirrhosis – A Tell-Tale Sign of Compromised Immunity?

BackgroundBacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections.Methodology/Principal FindingsSera of 676 patients with various chronic liver diseases (autoimmune diseases:266, viral hepatitis C:124, and liver cirrhosis of different etiology:286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae(ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p = 0.003), as well as multiple seroreactivity (p = 0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR:1.62, 95%CI:1.16–2.25), co-morbidities (OR:2.22, 95%CI:1.27–3.86), and ASCA positivity (OR:1.59, 95%CI:1.07–2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p = 0.03) and multiple seropositivity (p = 0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p = 0.018, OR:1.85) and co-morbidities (p<0.001, OR:2.02) by Cox-regression analysis.Conclusions/SignificanceThe present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies.

T1284 Anti- Saccharomyces Cerevisiae Antibody (ASCA) is a Useful Diagnostic Tool to Differentiate Crohn's Disease From Intestinal Tuberculosis

T1284 Anti- Saccharomyces Cerevisiae Antibody (ASCA) is a Useful Diagnostic Tool to Differentiate Crohn's Disease From Intestinal Tuberculosis

Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability

Various genes may influence intestinal barrier function, including MAGI2, MYO9B, and PARD3, which are associated with celiac disease. Because direct measurement of intestinal permeability is difficult, antibodies against gliadin (AGA) and Baker's yeast (anti- Saccharomyces cerevisiae antibodies [ASCA]) can be used as an indirect test. The objective of this study was to investigate whether intestinal permeability, represented by AGA, was correlated with MAGI2, MYO9B, and PARD3. Analyses were performed in patients with Down syndrome, a population with suspected increased intestinal permeability. Correlations between AGA and ASCA were investigated. Patients with Down syndrome ( n = 126) were genotyped for six single-nucleotide polymorphisms in MAGI2 (rs1496770, rs6962966, rs9640699), MYO9B (rs1457092, rs2305764), and PARD3 (rs10763976). An allele dosage association of these risk genes and AGA levels was performed. The correlation between AGA and ASCA was studied. A strong correlation was found between AGA and ASCA ( p < 0.01). The patient group with one or more risk genotypes had lower mean AGA levels (trend test p = 0.007) and consisted of a larger number of patients with normal AGA levels ( p = 9.3 × 10 −5). Celiac-associated risk genotypes are associated with lower AGA values instead of elevated ones. Thus, other immunologic phenomena play a role in the increased prevalence of elevated AGA in patients with Down syndrome, possibly involving altered induction and/or maintenance of tolerance.

Mannose-binding lectin level and deficiency is not associated with inflammatory bowel diseases, disease phenotype, serology profile, and NOD2/CARD15 genotype in a large Hungarian cohort

Mannose-binding lectin (MBL) is a major, soluble, pattern-recognition molecule and an important component of the innate host defense. The role of MBL in inflammatory bowel diseases (IBDs) is controversial. We determined the prevalence of MBL deficiency in a Hungarian IBD patients' cohort, and whether it is associated with the antimicrobial antibody formation or particular clinical manifestations. Nine hundred ninety IBD patients and 225 healthy subjects were investigated. Sera were assayed for MBL and a panel of antimicrobial antibodies (anti-OMP, anti- Saccharomyces cerevisiae antibodies, and antiglycans) by ELISA. TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. Median MBL level was not significantly different between IBDs (Crohn's disease [CD]: 929; ulcerative colitis [UC]: 810 ng/ml) and the control group (1027 ng/ml), as well as the prevalence of absolute MBL deficiency (<100 ng/ml) (CD: 15.0%, UC: 18.4%, controls: 15.6%). The presence of a low MBL level (<500 ng/ml) was not associated with any of the examined serologic markers, or their combinations. In addition, there was no association with the clinical presentation, disease course, or response to treatment. TLR4 variant genotype was more common in CD patients without MBL deficiency (11% vs. 1.7%, OR: 7.29, 95% CI: 1.08–53.9, p = 0.02). We failed to confirm any association between MBL deficiency and serologic marker positivity. MBL deficiency was not predictive for clinical phenotype or disease activity in IBDs.

NOD2 Mutations and Anti- Saccharomyces cerevisiae Antibodies Are Risk Factors for Crohn's Disease in African Americans

NOD2 mutations and anti-Saccharomyces cerevisiae antibodies (ASCAs) are established risk factors of Crohn's disease (CD) in whites but have not been assessed in African-American (AA) adults with CD. AAs with CD and controls were recruited by the Mid-Atlantic African-American IBD Study as part of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium. Genotyping for the three common CD NOD2 mutations (Leu1007fsinsC, G908R/2722g>c, and R702W/2104c>t) and ASCA enzyme-linked immunosorbent assays were performed in 183 AA CD patients and in 143 controls. Logistic regression was used to calculate adjusted odds ratios (ORs) for the association between ASCA and disease phenotype. ASCA sensitivity and specificity values were 70.5 and 70.4%, respectively. On univariate analysis, ASCA was significantly associated with younger age at diagnosis, ileal involvement, and complicated (stricturing/penetrating) behavior. On multivariate analysis, ASCA titer (per 25 Units) was associated with ileal involvement (OR 1.18, 95% confidence interval (CI): 1.04-1.34), complicated behavior (OR 1.13, 95% CI: 1.01-1.28), and surgery (hazard ratio: 1.11, 95% CI: 1.02-1.21). Cigarette smoking and CD family history were also significantly associated with surgery. NOD2 carriers (all heterozygotes) were more common among CD cases than controls (8.2 vs. 2.1%; OR 4.17%, 95% CI: 1.18-14.69). The NOD2 mutation population attributable risk was 6.2%. In comparison with whites, ASCA in AAs has a similar sensitivity but a lower specificity for CD. ASCA is associated with ileal involvement, complicated behavior, and surgery in AAs with CD. NOD2 is a risk gene for AA CD, although mutation frequency and population attributable risk are much lower than in whites.

P280 - Faecal calprotectin remains stable in inactive Crohn's disease patients

P280 - Faecal calprotectin remains stable in inactive Crohn's disease patients

P281 - The prevalence of antibodies against cyclic citrullinated peptide (anti-CCP) is low in patients with inflammatory bowel disease with or without arthritis

P281 - The prevalence of antibodies against cyclic citrullinated peptide (anti-CCP) is low in patients with inflammatory bowel disease with or without arthritis

Infliximab in clinical routine: experience with Crohnʼs disease and biomarkers of inflammation over 5 years

Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab. To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA). During 1999-2008, CD patients were monitored for disease activity by Harvey-Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies. A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey-Bradshaw index decreased with infusions during the first year of treatment (P < 0.0001), whereas hemoglobin (P < 0.01) and albumin (P <0.001) increased, C-reactive protein (P < 0.01) decreased, platelets (P <0.001) increased, and leukocytes (P< 0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P < 0.0001), and nitrite (P < 0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found. Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.