IgA-coated enriched in Crohn's disease spondyloarthritis promote T17-dependent inflammation.

TitleIgA-coated enriched in Crohn's disease spondyloarthritis promote T17-dependent inflammation.
Publication TypeJournal Article
Year of Publication2017
AuthorsViladomiu M, Kivolowitz C, Abdulhamid A, Dogan B, Victorio D, Castellanos JG, Woo V, Teng F, Tran NL, Sczesnak A, Chai C, Kim M, Diehl GE, Ajami NJ, Petrosino JF, Zhou XK, Schwartzman S, Mandl LA, Abramowitz M, Jacob V, Bosworth B, Steinlauf A, Scherl EJ, Wu H-JJoyce, Simpson KW, Longman RS
JournalSci Transl Med
Date Published2017 02 08
KeywordsAnimals, Biomarkers, Colitis, Crohn Disease, Dextran Sulfate, Epithelium, Escherichia coli, Humans, Immunity, Mucosal, Immunoglobulin A, Immunophenotyping, Inflammation, Interleukin-10, Interleukin-23, Intestines, Joints, Mice, Inbred C57BL, Spondylarthritis, Th17 Cells

Peripheral spondyloarthritis (SpA) is a common extraintestinal manifestation in patients with active inflammatory bowel disease (IBD) characterized by inflammatory enthesitis, dactylitis, or synovitis of nonaxial joints. However, a mechanistic understanding of the link between intestinal inflammation and SpA has yet to emerge. We evaluated and functionally characterized the fecal microbiome of IBD patients with or without peripheral SpA. Coupling the sorting of immunoglobulin A (IgA)-coated microbiota with 16 ribosomal RNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coated in patients with Crohn's disease-associated SpA (CD-SpA) compared to CD alone. isolates from CD-SpA-derived IgA-coated bacteria were similar in genotype and phenotype to an adherent-invasive (AIEC) pathotype. In comparison to non-AIEC , colonization of germ-free mice with CD-SpA isolates induced T helper 17 cell (T17) mucosal immunity, which required the virulence-associated metabolic enzyme propanediol dehydratase (). Modeling the increase in mucosal and systemic T17 immunity we observed in CD-SpA patients, colonization of interleukin-10-deficient or K/BxN mice with CD-SpA-derived lead to more severe colitis or inflammatory arthritis, respectively. Collectively, these data reveal the power of IgA-seq to identify immunoreactive resident pathosymbionts that link mucosal and systemic T17-dependent inflammation and offer microbial and immunophenotype stratification of CD-SpA that may guide medical and biologic therapy.

Alternate JournalSci Transl Med
PubMed ID28179509
PubMed Central IDPMC6159892
Grant ListK08 DK099381 / DK / NIDDK NIH HHS / United States
R01 AI107117 / AI / NIAID NIH HHS / United States
R56 AI107117 / AI / NIAID NIH HHS / United States