Trafficking of antigens from gut to sacroiliac joints and spine in reactive arthritis and spondyloarthropathies: Mainly through lymphatics?

Bacterial trafficking from gut to mesenteric lymph nodes is physiologic only for a few commensal species, like Alcaligenes which produces antimicrobial-substances inhibiting growth of pathogenic bacteria. In reactive arthritis, some living bacteria transiently manage to travel from gut to joints/enthesis within dendritic cells and/or macrophages. Migration of dead or dormant bacteria outside the gut in spondyloarthropathies, including those associated with Crohn's disease, can occur either through blood or lymphatics. Migration through lymphatics instead of blood depends on the host, but also on the subset of pathogen, as shown for Salmonella. Retrograde trafficking within lymphatics of immune cells infected by dormant or dead bacteria, from mesenteric lymph nodes or thoracic duct to sacroiliac joint and spine, might contribute to axial involvement in some spondyloarthropathies and related disorders, since: 1- large influxes of pathogens can overwhelm lymph nodes, and Yersinia can even replicate within lymph nodes; 2- Whipple cells have been shown to circulate in thoracic duct lymph; 3- expansion of lymphatics is a prominent feature of gastro-intestinal inflammation, and obstruction of gut lymphatics a hallmark of Crohn's disease; 4- lymph reflux has been demonstrated in models of mesenteric lymph vessel obstruction; 5- reflux to sacroiliac has been observed in patients with chyluria undergoing lymphography; 6- lymphatics are present in the outer periosteum and paraspinal ligaments surrounding intervertebral discs and connected to thoracic duct. Accordingly, further studies on the trafficking of dendritic cells, macrophages and lymphocytes from gut to joints and spine in animal models of reactive arthritis or spondyloarthropathies should also focus on lymphatic routes.