P1446 - Serum IgA Levels Are Significantly Decreased After Rifaximin Therapy in Patients With Diarrhea-Predominant Irritable Bowel Syndrome Whose Inflammatory State May Be Linked to Anti-Vinculin Antibodies

Award: Presidential Poster Award

Award: Presidential Poster Award

Walter Morales, ¹, Gonzalo Parodi, ¹, Brennan Chuang, ¹, Stacy Weitsman, MS¹, Ruchi Mathur, MD², Ali Rezaie, MD³, Mark Pimentel, MD⁴, Gabriela Leite, PhD^1
1Cedars-Sinai Medical Center - MAST Program, West Hollywood, CA; ²Cedars-Sinai Medical Center - MAST Program, Los Angeles, CA; ³Cedars Sinai Medical Center - MAST Program, West Hollywood, CA; ⁴Cedars-Sinai Medical Center, West Hollywood, CA

Introduction: The role of immunoglobulins such as IgG, IgM, and IgA in gut immunity has expanded from controlling commensal and pathogenic bacteria at mucosal barriers to include an intricate role in our systemic immunity. Studies have shown that select commensal bacteria induce facets of systemic IgA-mediated immunity. In diarrhea-predominant IBS (IBS-D), autoantibodies to vinculin are produced in response to acute gastroenteritis. In this study, we evaluate the effect of rifaximin treatment on serum autoimmunity and immunoglobulins, bridging an underlying immunologic complexity with its treatment in IBS-D patients.

Methods: IBS-D patients, diagnosed under Rome III criteria that presented with abdominal pain, bloating, and “loose stool” for at least 2 out of 7 days were recruited into the study. Upon inclusion, patients received rifaximin 550mg TID for 2 weeks. Blood samples were collected pre- and post-treatment. Samples were evaluated for simultaneous analysis of IgA, IgM, IgG1, IgG2, IgG3, and IgG4 on the FlexMap 3D (Luminex, Austin, TX) using the MILLIPLEX® MAP Human Isotyping kit (Millipore, Burlington, MA). In addition, serum was used to assess the level of anti-vinculin antibodies.

Results: 30 IBS-D patients were included. The cohort was 67% female with an average age of 40.60±13.66 years. Post-treatment blood was collected, on average, 19.9 days after baseline. Baseline serum IgA was 1.33±0.72 g/L. The IgA levels were significantly lowered after treatment (0.96±0.50 g/L) (p< 0.0001) (Figure 1a). This change was related to rifaximin in general and was not related to whether patients responded to rifaximin or not. Levels of IgM, IgG1, IgG2, IgG3, IgG4 were not significantly different from baseline after treatment. Anti-vinculin levels were measured at baseline and after treatment. There were no changes in anti-vinculin levels with rifaximin treatment. However, the level of anti-vinculin antibodies correlated with overall levels of IgG4 (Spearman r_s=0.411, p=0.027) (Figure 1b).

Discussion: In this study, for the first time, we demonstrate a reduction in IgA levels with the use of rifaximin to treat subjects with IBS-D. This may reflect a change in the response to luminal antigens such as bacteria. Autoantibodies to vinculin are associated with IgG4, a subclass associated with systemic, multi-organ autoimmune diseases. Further study into serum immunoglobulins, links to the microbiota of IBS-D patients, and a multifactorial action of rifaximin is needed.



Disclosures:


Walter Morales, ¹, Gonzalo Parodi, ¹, Brennan Chuang, ¹, Stacy Weitsman, MS¹, Ruchi Mathur, MD², Ali Rezaie, MD³, Mark Pimentel, MD⁴, Gabriela Leite, PhD¹. P1446 - Serum IgA Levels Are Significantly Decreased After Rifaximin Therapy in Patients With Diarrhea-Predominant Irritable Bowel Syndrome Whose Inflammatory State May Be Linked to Anti-Vinculin Antibodies, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.