Multiplexed Imaging to Improve and Define Diagnosis and Subsequent Treatment for Patient Suffering from Gulf War Illness Using CyTOF and Codex
Abstract
Inflammation-associated gastrointestinal difficulties such as chronic diarrhea, bloating, constipation, abdominal pain are among the most prevalent shared symptoms in patients with Gulf War Illness (GWI), and pose a significant challenge to Veteran quality of life. These difficulties are currently being addressed by two primary strategies. The first directly targets the bacterial communities that naturally reside in the gut, which evidence suggests may be altered in patients with GWI. While dietary restrictions appear to ameliorate symptoms, direct modification of these communities has not yielded improvements in quality of life. The second approach directly uses anti-inflammatories, most notably the TNF-blockers used in more widespread autoimmune disorders such as inflammatory bowel disease (IBD) and rheumatoid arthritis, and holds substantial promise for treating GI symptoms. However, evidence from IBD and rheumatoid arthritis indicates that these therapies often encounter high (up to 50%) resistance rates, and have considerable side effects. Our previous work in IBD suggests that this resistance can be predicted based on how inflammatory cells are spatially arranged; resistance cannot be sufficiently predicted without taking spatial context into account. Here, we propose a pilot study to investigate the potential for adapting our insights from IBD patients to the treatment of GWI patients. We first propose to examine the cellular profiles in patient blood to determine which patients are the most severely affected by inflammation. Since the location of the inflammation in the GWI gut is not yet known, we then propose to obtain biopsies, from patients with the strongest inflammatory signatures, throughout the length of the patient GI tract. These samples will be quickly screened for inflammatory signatures, followed by an in-depth, spatial analysis of the most affected samples. We will specifically look for spatial cell arrangements similar to those we have previously observed in IBD, especially those associated with treatment resistance. Finally, we will perform a preliminary visualization of the local bacterial communities, to see how bacterial communal structures impact inflammatory cellular arrangements. If successful, this grant will demonstrate the potential for guiding anti-inflammatory treatment in GWI patients, while dramatically contributing to the body of knowledge regarding gut-associated GWI inflammation. Insights from this grant could readily be applied in a clinical setting within several years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110670
Entities
People
- Stephan Rogalla
Organizations
- Stanford University
- United States Army