Su1792 Factors Contributing to Indeterminate QuantiFERON®-TB Gold In-Tube Test Results in Patients With Inflammatory Bowel Diseases

Breath Methane and Hydrogen Composition in Inflammatory Bowel Disease (IBD) Is Strikingly Different From Non-IBD Patients and Is Associated With IBD-Associated Genes: A Large-Scale Database Linkage Analysis Ali Rezaie, Mark Pimentel, Bianca W. Chang, Dana Pan, Kathleen Shari Chua, Greg Lentz, Matthew Sonesen, Renier Estiandan, Eric Vasiliauskas, Stephan Targan, Xiaofei Yan, Dalin Li, Dermot McGovern Introduction: In IBD patients who exhibit overlapping irritable bowel syndrome (IBS)-like symptoms gut microbial dysbiosis and small intestinal bacterial overgrowth (SIBO) have been implicated. As such, there has been increasing interest for the use of breath testing (BT) in IBD, as a simple and non-invasive diagnostic tool. In non-IBD patients overgrowth of hydrogen (H2) or hydrogen sulfide (H2S) producing bacteria lead to diarrhea and excessive methane (CH4) production is associated with constipation. We sought to characterize the BT patterns of IBD patients as compared to non-IBD and explore the IBD-related gene and serology associations. Methods: A database of 14,847 consecutive lactulose BTs, performed between Nov 2005 and Oct 2013 was developed. Repeated BTs were excluded using probabilistic record linkage. BTs were classified into 4 categories: Normal: CH4 <10 parts per million (ppm) and H2 rise <20 ppm within 90 min, H2-predominant SIBO: CH4<10 ppm and H2 rise >20 ppm within 90 min, Excessive CH4 producer: CH4 ‡10 ppm, Flatline: CH4 = 0 ppm and H2£3 ppm with variation £1 ppm within 120 min. BT data was linked to our IBD database (n= 5537) to identify IBD patients and their clinical history, phenotype (Montreal classification), genotype and IBD associated serology. Subjects with known ulcerative colitis (UC) or Crohn's disease (CD) were compared to non-IBD patients with IBS-like symptoms. Results: Of 12,340 subjects with a BT, 211 CD, 99 UC and 12,030 non-IBD patients with IBS-like symptoms were identified. (Table 1) H2+ SIBO was prevalent in CD, UC and nonIBD patients (range 39-47%, p=0.2). (Fig 1) Patients with CD (OR=0.18; 95% CI, 0.380.07) and UC (OR=0.4; 95% CI, 0.91-0.16) were significantly less likely to produce excessive CH4 compared to non-IBD patients. All CD patients (7/7) and 2/7 UC patients with excessive CH4 production experienced severe constipation. Flatline BT was significantly more prevalent in CD (OR=2.6; 95% CI 1.5-4.4). BT pattern had no association with disease phenotype. Flatline BT was associated with the known FUT2 IBD associated SNP (OR=0.3, p= 0.002) and also a FUT1 SNP (OR 10.1, p= 9.9x 10-5). Excess CH4 production was associated with known IBD locus CD226 (OR. 6.4, p= 0.0049). Excessive CH4 producers with UC have lower OmpC antibodies than other UC patients (p=0.01). Conclusion: SIBO is frequently present in IBD patients with IBS-like symptoms. Methanogenesis is significantly suppressed in IBD patients; however, if present it is associated with severe constipation especially in CD. A flatline breath test is more prevalent in CD which may suggest excessive H2S production. Genetic variants in fucosyltransferase genes (FUT1 and FUT2) are associated with flatline BT. Further evaluation and characterization of IBD-SIBO associations may allow for development of novel approaches to treat overlapping IBD-IBS symptoms. Table 1. Patient characteristics and phenotype.

Figure 1: Denotes in vitro data on. A) protein expression in LPS+CaCl treated cells and controls by western blotting, B) morphological cell changes and anti-vimentin immunosflourescense and DAPI stainings on LPS+CaCl treated cells and controls C) VICM levels in supernatants from LPS + CaCl treated cells and controls by ELISA. **:P<0.01, ***:P<0.001 *Montreal classification Su1792 Factors Contributing to Indeterminate QuantiFERON®-TB Gold In-Tube Test Results in Patients With Inflammatory Bowel Diseases Prianka Singapura, Aylin Tansel, Neeharika Kalakota, Guillermina Cruz, Jose-Miguel Yamal, Manreet Kaur BACKGROUND: QuantiFERON®-TB Gold in-tube (QFT-G) test is widely used to screen for latent mycobacterium tuberculosis in patients with inflammatory bowel diseases (IBD) prior to initiation of anti tumor necrosis factor (anti-TNF) therapy. A significant proportion of these tests are reported as indeterminate; prompting additional testing. The aim of this study was to evaluate factors associated with indeterminate QTF-G test results among patients with IBD. METHODS: Adults with QFT-G test results and a concomitant diagnosis of IBD receiving their care at a tertiary referral center between 2011-2013 were included. We performed a case control study comparing IBD patients with indeterminate and determinate (positive or negative) results on QFT-G test. Data on demographics, clinical features, laboratory parameters and medication use were obtained by chart review. Univariate analyses were performed using Chi-square test for categorical and Wilcoxon rank sum test for continuous variables. Variables with p-value less than 0.25 were included in the multiple logistic regression model. Backwards selection was employed with significance level of 0.05. Odds ratio (OR) from logistic regression and their 95% confidence interval (CI) were reported. RESULTS: A total of 205 patients with IBD (112 Crohn's disease and 93 ulcerative colitis) were included in the final analyses. Indeterminate results were noted in 22.4% of patients. Patients with indeterminate QFT-G results were more likely to be on systemic corticosteroid therapy [65.2% vs 44%, p= 0.01], have lower hemoglobin levels [11.7 g/dl vs 12.7g/dl, p= 0.001], higher eryrthrocyte sedimentation rate (ESR) (26.2 vs 17.4, p= 0.02), higher Creactive protein (CRP) levels (3.1 mg/dl vs 1.8 mg/dl, p= 0.01) and lower serum albumin levels (3.8 g/dl vs 4.2 g/dl, p < 0.0001). On multivariable analyses corticosteroid use [OR= 2.57; 95% CI, 1.17- 5.66, p= 0.02] and albumin levels (OR= 0.42; 95%CI, 0.19-0.93, p= 0.03) remained significantly associated with indeterminate QFT-G results. CONCLUSION: Systemic corticosteroid treatment was associated with an increased likelihood of having an indeterminate result on QFT-G test in patients with IBD.

Figure 1. Percentage of breath test categories in non-IBD patients with IBS-like symptoms, CD and UC. P values correspond to the comparisons with non-IBD group. There is no statistically significant difference between breath test patterns of CCD and UC patients.

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AGA Abstracts

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