Fecal Calprotectin Concentrations in Cats with Chronic Enteropathies

Abstract

Diagnosis of feline chronic inflammatory enteropathies (CIE) and the differentiation from small cell intestinal lymphoma (SCL) can be challenging. Intestinally expressed calprotectin (S100A8/A9 protein complex) appears to be part of the complex pathogenesis of feline chronic enteropathies (FCE). Fecal calprotectin is a non-invasive biomarker for intestinal inflammation in humans and dogs but has not yet been evaluated in cats. We hypothesized that fecal calprotectin (fCal) concentrations are increased in FCE, correlate with clinical and/or histologic disease severity, and distinguish cases of CIE from SCL. This case-control study included fecal samples and patient data from cats with CIE (n = 34), SCL (n = 17), other gastrointestinal (GI) diseases (n = 16), and cats with no clinical signs of GI disease (n = 32). fCal concentrations were measured using the immunoturbidimetric fCal turbo assay (Bühlmann Laboratories). Compared to healthy cats, fCal concentrations were significantly increased in CIE, SCL, and other diseases (all p < 0.0001), but were not different between these three groups (all p > 0.05), or between cats with extra-GI diseases and healthy controls. These findings suggest that fCal may have utility as a clinical biomarker for FCE but not for intestinal disease differentiation. It further supports the role of calprotectin in the pathogenesis of the spectrum of FCE, which includes CIE and SCL.

Keywords: biomarker; feline chronic enteropathy; food-responsive enteropathy; gastrointestinal diet; hydrolyzed diet; inflammatory bowel disease; small cell lymphoma; steroid-responsive enteropathy.

Figure 1

Flowchart of all cats with the differential diagnosis of chronic enteropathy included in the study and those cats with complete follow-up information. Abbreviations: CE = chronic enteropathy; CIE = chronic inflammatory enteropathy; CR = complete remission; DD = differential diagnosis; FRE = food-responsive enteropathy, GI = gastrointestinal; IRE = immunosuppressant-responsive enteropathy; n = number (count); NR = no response; SCL = small-cell lymphoma; PR = partial remission. State of remission was based on clinical signs, partial remission in SCL cases was defined as “stable disease”. Classification as PR or CR was not documented for 4 cats in the CIE group.

Figure 2

Violin plot showing fecal calprotectin (fCal) concentrations in all cats (n = 99) included in the study. All disease groups of cats had significantly higher fCal concentrations than healthy control cats (all p < 0.0001), with no differences among cats with chronic inflammatory enteropathy (CIE), small-cell alimentary lymphoma (SCL), or other gastrointestinal (GI) or extra-GI diseases (all p > 0.05). A total of 22 cats in the CIE group, 10 cats in the SCL group, 7 cats in the diseased control group, and all of the healthy controls had fCal levels within the reference interval. Gray-shaded area below the horizontal dashed line represent the reference interval (<64 µg/g) [43]. Note the broken y-axis.

Figure 3

Violin plot showing fecal calprotectin (fCal) concentrations in all 7 groups of cats enrolled in the study. Fecal calprotectin concentrations did not distinguish cases of food-responsive enteropathy (FRE; median: 45 µg/g, IQR: 14–258 µg/g) from immunosuppressant-responsive enteropathy (IRE; median: 63 µg/g, IQR: 28–324 µg/g; p = 0.5189) or small-cell intestinal lymphoma (SCL; median: 50 µg/g, IQR: 21–181 µg/g; p = 0.9842). Fecal calprotectin concentrations were highest in cats with acute gastrointestinal (GI) disease (median: 168 µg/g, IQR: 6–540 µg/g), with no significant difference compared to any chronic enteropathy group (all p > 0.05). Cats with extra-GI disease had the lowest fCal concentrations (median: 10 µg/g, IQR: 3–118 µg/g), showing no difference from healthy controls (p = 0.6919). Cats with other GI diseases (e.g., neoplasia) could not be included in the statistical analysis due to the small group size. Gray-shaded area below horizontal dashed line: reference interval (<64 µg/g) [43]. Note the broken y-axis.

Figure 4

Violin plot showing fecal calprotectin concentrations in cats with IRE and complete follow-up (n = 11) included in the study. Fecal calprotectin concentrations were numerically higher in cats with IRE and partial or no response (PR/NR) to treatment (median: 63 µg/g, IQR: 31–444 µg/g) compared to those cats with complete clinical remission (CR; median: 28 µg/g, IQR: 8–143 µg/g) but the difference was not statistically significant (p = 0.1564). Gray-shaded area below horizontal dashed line: reference interval (<64 µg/g) [43].