Autoimmune rheumatologic diseases

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Gut-derived Tnf as Risk Factor for the Development of Sacroiliac Inflammation

Thursday, June 15
5:45 PM - 7:00 PM

An intruiging link exists between gut and joint inflammation in spondyloarthritis (SpA), with about 50% of SpA patients having subclinical gut inflammation, which represents a risk factor for development of Crohn's disease, sacroiliitis and evolution into ankylosing spondylitis. However, the underlying mechanisms are still relatively poorly understood. Our goal was to examine the relationship between TNF, microscopic gut inflammation and axial inflammation. Therefore we examined in situ expression of TNF, TNFR1 and TNFR2 using triple in situ hybridisation in gut biopsies of human SpA patients and found marked upregulation of TNF, TNFR1 and TNFR2 in inflamed versus non-inflamed biopsies. In line with this, we found that patients with gut inflammation had a higher need for anti-TNF therapy and their degree of clinical response after anti-TNF was also markedly higher. We speculated that TNF in the gut represents an important risk factor for disease severity and progression in SpA. To investigate this further we generated a mouse-model over-expressing human TNF in the ileum. These mice, together with wild type littermates, were evaluated for the development of arthritis up until the age of 13 weeks. Transgenic mice exhibit a runt phenotype and hallmarks of inflammatory bowel disease. While in peripheral joints no clear signs of arthritis were observed, the sacroiliac joints in transgenic mice, by contrast, showed marked signs of inflammation. These data propose a new paradigm that gut-derived TNF is sufficient to trigger sacroiliitis and provide an alternate explanation on the relationship between gut inflammation and axial inflammation in SpA.

Karlijn Debusschere

PhD-student
UGent - IRC-VIB

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    Heleen Cypers

    Ghent University

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      Peggy Jacques

      Ghent University

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        Filip Van den Bosch

        Ghent University - UZ Gent

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          Donald Souza

          Senior Scientist
          Boehringer Ingelheim

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            Maryanne Brown

            Senier principal scientist
            Boehringer Ingelheim

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              Gerald Nabozny

              Executive director Immunology and Respiratory Diseases Research
              Boehringer Ingelheim

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                Devan Dove

                Scientist
                Boehringer Ingelheim

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                  Alexander Klimowicz

                  Principal scientist
                  Boehringer Ingelheim

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                    Dirk Elewaut

                    UGent-IRC VIB

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