Walter Morales1, Ali Rezaie1, Gillian Barlow1, Mark Pimentel2. 1. Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 240E, Los Angeles, CA, 90048, USA. 2. Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 240E, Los Angeles, CA, 90048, USA. pimentelm@cshs.org.
Abstract
BACKGROUND: ELISA testing for anti-CdtB and anti-vinculin can discriminate patients with irritable bowel syndrome with diarrhea (IBS-D) from those with inflammatory bowel disease (IBD). However, recent findings suggest the antigens can suffer from epitope instability. AIM: This study aimed to assess effects of incorporating epitope stabilization on test characteristics for distinguishing IBS-D from IBD subjects. METHODS: Plasma samples from IBS-D subjects from a large-scale clinical trial and subjects with endoscopically active IBD without concurrent immunomodulator therapy were used. After epitope stabilization, CdtB and vinculin were used in ELISA testing. Optical density readings were compared between IBS-D and IBD subjects. RESULTS: Samples from 100 IBS-D and 31 IBD (22 UC and 9 CD) subjects were tested. IBS-D subjects had higher anti-CdtB titers (P = 0.0001) and higher anti-vinculin titers (P = 0.004) than IBD subjects. The specificities of anti-CdtB and anti-vinculin to differentiate IBS-D from IBD were 93.5% and 90.9%, respectively, with sensitivities of 43.0% and 52.2%, respectively. The positive likelihood ratios of identifying IBS-D with anti-CdtB and anti-vinculin were 6.7 and 5.7, respectively. Assuming a pretest probability of 57% for diagnosis of IBS-D in patients with abdominal pain and change in bowel habits, testing positive for both antibodies resulted in a posttest probability of > 98%. CONCLUSIONS: Performing epitope stabilization for CdtB and vinculin enhances the test characteristics of ELISAs for anti-CdtB and anti-vinculin in discriminating IBS-D from IBD. Measurement of anti-CdtB and anti-vinculin with this second-generation methodology may further advance our understanding of the role of immunity in functional bowel diseases.
BACKGROUND: ELISA testing for anti-CdtB and anti-vinculin can discriminate patients with irritable bowel syndrome with diarrhea (IBS-D) from those with inflammatory bowel disease (IBD). However, recent findings suggest the antigens can suffer from epitope instability. AIM: This study aimed to assess effects of incorporating epitope stabilization on test characteristics for distinguishing IBS-D from IBD subjects. METHODS: Plasma samples from IBS-D subjects from a large-scale clinical trial and subjects with endoscopically active IBD without concurrent immunomodulator therapy were used. After epitope stabilization, CdtB and vinculin were used in ELISA testing. Optical density readings were compared between IBS-D and IBD subjects. RESULTS: Samples from 100 IBS-D and 31 IBD (22 UC and 9 CD) subjects were tested. IBS-D subjects had higher anti-CdtB titers (P = 0.0001) and higher anti-vinculin titers (P = 0.004) than IBD subjects. The specificities of anti-CdtB and anti-vinculin to differentiate IBS-D from IBD were 93.5% and 90.9%, respectively, with sensitivities of 43.0% and 52.2%, respectively. The positive likelihood ratios of identifying IBS-D with anti-CdtB and anti-vinculin were 6.7 and 5.7, respectively. Assuming a pretest probability of 57% for diagnosis of IBS-D in patients with abdominal pain and change in bowel habits, testing positive for both antibodies resulted in a posttest probability of > 98%. CONCLUSIONS: Performing epitope stabilization for CdtB and vinculin enhances the test characteristics of ELISAs for anti-CdtB and anti-vinculin in discriminating IBS-D from IBD. Measurement of anti-CdtB and anti-vinculin with this second-generation methodology may further advance our understanding of the role of immunity in functional bowel diseases.
Authors: A Lupascu; M Gabrielli; E C Lauritano; E Scarpellini; A Santoliquido; G Cammarota; R Flore; P Tondi; P Pola; G Gasbarrini; A Gasbarrini Journal: Aliment Pharmacol Ther Date: 2005-12 Impact factor: 8.171
Authors: Luis Alberto Bravo-Vázquez; Ixchel Medina-Ríos; Luis David Márquez-Gallardo; Josué Reyes-Muñoz; Francisco I Serrano-Cano; Surajit Pathak; Antara Banerjee; Anindya Bandyopadhyay; Asim K Duttaroy; Sujay Paul Journal: Dig Dis Sci Date: 2022-05-04 Impact factor: 3.487