Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: The microbiome is hypothesized to influence human health and disease. Changes in resident bacteria, termed dysbiosis, occur in spondyloarthritis (SpA) and inflammatory bowel disease (IBD), which is subdivided into Crohn’s Disease (CD) and Ulcerative Colitis (UC). However, the immunologic consequences of dysbiosis in SpA and IBD have not been established. Intraepithelial lymphocytes (IELs) are T cells within the intestinal epithelium that are in close contact with bacteria. As such, they are prime candidates to link the microbiome with downstream immune functions that result in SpA and IBD. We sought to correlate IELs with resident bacteria in individuals with SpA and IBD relative to controls.
Methods: Subjects with biopsy-proven IBD, axial SpA fulfilling ASAS criteria, and controls undergoing standard of care colonoscopies were recruited. Subjects with antibiotic use within two weeks, NSAID use, other rheumatic diseases, and enteropathic arthritis were excluded. A rectal swab was obtained for microbiome analysis by 16S sequencing and peripheral blood was analyzed for WBC, CRP, and HLAB27. Colonic pinch biopsies of grossly normal-appearing tissue from all participants were obtained during routine colonoscopy or research flexible sigmoidoscopy. IELs were harvested from the biopsies and characterized by flow cytometry for the surface markers CD3, CD4, CD8α, CD8β, CD45, TCRγδ, and TCRβ. Secreted cytokines, TNF-α, IFN-γ, IL-6, and IL-17A, were measured by ELISA in the supernatants of mitogen stimulated IELs. Cytokine secretion were then ranked and analyzed. Statistical analyses were performed with Kruskal-Wallis and Spearman’s Rank.
Results: Thus far 13 controls, 10 cases of CD, 6 cases of UC, and 4 patients with SpA have been evaluated. Our preliminary data demonstrates IELs from subjects with CD had increased IL-17A, (p=0.03) TNF-α, (p=0.04) and IFN-γ (p<0.01) whereas UC had higher IL-1β compared to CD (p=0.03) or controls (p=0.03). Evaluating cytokines in relationship to the microbiome revealed a correlation between TNFα and the Simpson Index of Diversity in UC (Spearman’s rank=0.943, p<0.01). In CD, Fusobacterium had negative correlation with TNFα+ IFNγ + IL-1β (Spearman’s rank=-0.786, p=0.02). These relationships were not seen in other groups. The recruited SpA patients so far are all HLAB27 positive Caucasian males with a mean age of 35.8. They had been diagnosed an average of 8.5 years ago and had an average BASDAI of 5.2, and CRP of 10.8 mg/L. Preliminary data of the SpA patients suggests the presence of dysbiosis and a trend towards less IELs compared to controls (p=0.08).
Conclusion: Our data indicate differences in IEL populations between UC, CD, and controls. SpA patients are being actively recruited and their data will be analyzed. Reviewing the results from our IBD cohort, we hypothesize that patients with SpA will also have higher levels of inflammatory cytokine expression than controls which will have their own unique relationships with colonic microbiota. Our study is relevant to the pathogenesis of SpA and IBD as it shows that IEL cytokine secretion is associated with dysbiosis and this correlation varies by disease type.
To cite this abstract in AMA style:Ohri N, Gerich M, Fennimore B, Ir D, Robertson C, Frank D, Caplan L, Wagner B, Kuhn K. Bacterial Dysbiosis Associates with Functional Intraepithelial Lymphocyte Changes in Inflammatory Bowel Disease and Spondyloarthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/bacterial-dysbiosis-associates-with-functional-intraepithelial-lymphocyte-changes-in-inflammatory-bowel-disease-and-spondyloarthritis/. Accessed July 11, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bacterial-dysbiosis-associates-with-functional-intraepithelial-lymphocyte-changes-in-inflammatory-bowel-disease-and-spondyloarthritis/