Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis

Abstract

IntroductionMicroscopic bowel inflammation is present in up to 50% of patients with spondyloarthritis (SpA) and is associated with more severe disease. Currently no reliable biomarkers exist to identify patients at risk. Calprotectin is a sensitive marker of neutrophilic inflammation, measurable in serum and stool.ObjectivesTo assess whether serum and faecal calprotectin in addition to C-reactive protein (CRP) can be used to identify patients with SpA at risk of microscopic bowel inflammation.MethodsSerum calprotectin and CRP were measured in 125 patients with SpA. In 44 of these patients, faecal samples were available for calprotectin measurement. All 125 patients underwent an ileocolonoscopy to assess the presence of microscopic bowel inflammation.ResultsMicroscopic bowel inflammation was present in 53 (42.4%) patients with SpA. Elevated serum calprotectin and CRP were independently associated with microscopic bowel inflammation. Faecal calprotectin was also significantly higher in patients with microscopic bowel inflammation. Patients with CRP and serum calprotectin elevated had a frequency of bowel inflammation of 64% vs 25% in patients with low levels of both. When either CRP or serum calprotectin was elevated, the risk was intermediate (40%) and measuring faecal calprotectin provided further differentiation. Hence we suggest a screening approach where initially serum calprotectin and CRP are assessed and, if necessary, faecal calprotectin. The model using this scenario provided an area under the ROC curve of 74.4% for detection of bowel inflammation.ConclusionsCalprotectin measurements in stool and serum, in addition to CRP, may provide a promising strategy to identify patients with SpA at risk of bowel inflammation and could play a role in overall patient stratification.

Calprotectin in rheumatic diseases

“…92,93 Other studies have described lower or similar CLP serum levels in patients with SpA compared with RA. 88,94 One study by Cypers et al…”

“…97 The mucosal contribution to the increase in circulating CLP levels may explain the modest correlation with SpA disease activity. 94 CLP decreases rapidly upon effective treatment with TNF-a-inhibitors and secukinumab in both axial and peripheral SpA and it has been suggested as a useful biomarker for disease monitoring, where it performs even better than high-sensitivity CRP. 91,95 Baseline CLP was also found to be an independent predictor of radiographic spinal progression in axial SpA in a cohort of German patients.…”

“…Indeed, almost no correlation was found between CLP and Ankylosing Spondylitis Disease Activity Score, 82 Bath AS disease activity index, or Bath AS functional index. 89,91,92,[94][95][96] Notably, CLP is secreted not only in the joints, but also in other inflamed tissues such as the gastrointestinal mucosa. Up to 50% of patients with SpA have subclinical bowel inflammation, which is associated with increased serum levels of CLP.…”

The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases

“…The diagnosis of intestinal inflammation in SpA is essentially made using endoscopy as reliable biomarkers are lacking. Recently, however, elevated serum calprotectin and C-reactive protein (CRP) were demonstrated to be independently associated with microscopic bowel inflammation [30]. During intestinal inflammation, fecal calprotectin is elevated because of the migration of neutrophils to the inflamed intestinal mucosa [31].…”

“…In this study, the authors suggested a screening approach where initially serum calprotectin, CRP, and, if necessary, fecal calprotectin are assessed. The model using this scenario provided an area of 74.4% under the Receiver Operating Characteristic (ROC) curve for the detection of bowel inflammation [30].…”