A case with Crohn’s disease-associated spondyloarthritis exhibiting enhanced pro-inflammatory cytokine responses to Toll-like receptor ligands
Hajime Honjo,1 Tomohiro Watanabe,1 Natsuki Okai,1 Masashi Kono,1 Ken Kamata,1 Kosuke Minaga,1 Yoriaki Komeda,1 Shigeyoshi Tsuji,2 Masatoshi Kudo1
1 Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka, Japan
2 Department of Orthopedics/Rheumatology, National Hospital Organization, Osaka Minami Medical Center, Kawachi-Nagano, Osaka, Japan
Abstract
Background: Despite the high incidence of spondyloarthritis (SpA) as an extra-intestinal manifestation of Crohn’s disease (CD), the immunopathogenesis of CD-associated SpA remains largely unknown.
Objective: We tried to explore molecular mechanisms accounting for the development of CD-associated SpA in a patient successfully treated with infliximab.
Methods: Peripheral blood mononuclear cells (PBMCs) before infliximab treatment were stimulated with Toll-like receptor (TLR) ligands to measure pro-inflammatory cytokine responses. Endoscopic biopsy samples before and after infliximab treatment were subjected to quantitative polymerase chain reaction.
Results: PBMCs from this CD-associated SpA patient exhibited higher production of pro-inflammatory cytokines upon stimulation with TLR ligands than PBMCs from healthy controls. Induction of remission by infliximab was associated with the downregulation of pro-inflammatory cytokine responses in the small intestinal mucosa, which is continually exposed to TLR ligands.
Conclusion: Excessive pro-inflammatory cytokine responses to TLR ligands might underlie the immunopathogenesis of CD-associated SpA.
Key words: Crohn’s disease, spondyloarthritis, Toll-like receptor, intestinal microflora, pro-inflammatory cytokines