Background/Purpose: Microscopic gut inflammation is present in about 50% of spondyloarthritis (SpA) patients. Two types can be distinguished: an acute type resembling infectious enterocolitis, and a chronic type similar to early Crohn’s disease. Although subclinical, microscopic gut inflammation appears to be a prognostic factor in SpA, linked with more extensive disease and a less favorable outcome. At this moment, however, reliable biomarkers are missing. The calgranulins S100A8/S100A9 and S100A12 are very sensitive markers of innate immune activation. They are released from monocytes and granulocytes in the early phase of the immune response and exert important pro-inflammatory effects via Toll-like receptor 4 dependent mechanisms. Calgranulins can be measured in serum and stool. Moreover, the S100A8/S100A9 heterodimer, also called calprotectin, has been established for a long time as a fecal marker of disease activity in inflammatory bowel disease. Our aim was to  assess whether calgranulins can be used as biomarkers for microscopic gut inflammation in SpA.

Methods: Serum levels of calgranulins were measured in 103 newly diagnosed SpA patients and 24 healthy controls. Ninety seven SpA patients underwent an ileocolonoscopy to assess the presence of microscopic gut inflammation. Ileal and colonic biopsies were histologically scored and subsequently immuno-stained for S100A8 and S100A9.

Results and Conclusion: Serum levels of S100A8/S100A9 and S100A12 were significantly higher in SpA patients versus healthy controls (p= 0,035 and p = 0,024). Levels correlated moderately with CRP, but not with ASDAS, BASDAI or swollen joint count. SpA patients with the acute type of microscopic gut inflammation (N= 17) had significantly higher calgranulin levels compared to those with normal gut histology (N= 56) (p = 0,021 for S100A8/S100A9 and p = 0,05 for S100A12). Furthermore, immunohistology showed high staining of S100A8 and S100A9 on acutely inflamed gut biopsies, compared to absent/minimal staining on normal biopsies. Chronically inflamed biopsies (N=24) stained positive only when they had high inflammatory activity (in ~ 50% of cases). Importantly, NSAID intake had neither influence on immunohistology stainings nor on serum levels of calgranulins. To conclude, we found that calgranulin levels, both systemically and locally, marked the presence of acute microscopic gut inflammation in SpA. These results illustrate their high sensitivity as they reflected inflammation present only on a subclinical level. Therefore we anticipate that they may be of particular value in detecting (or excluding) latent (systemic) disease.

Acknowledgements: The research leading to these results has received funding from the European Union’s 7^th Framework Program under EC-GA No.  305266  “MIAMI”.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/calgranulin-levels-are-elevated-in-spondyloarthritis-and-reflect-the-presence-of-acute-microscopic-gut-inflammation/