Untersuchungen zur Anwendung ausgewählter serologischer und fäkaler Biomarker und deren diagnostischen sowie prognostischen Nutzen bei Hunden mit chronischentzündlichen Entero

Studies on the use of selected serological and fecal biomarkers and their diagnostic and prognostic benefits in dogs with chronic inflammatory enteropathies

Canine chronic inflammatory enteropathies are multifactorial diseases, whose aetiopathogeneses have yet to be fully understood. A classification as food-responsive enteropathy (FRE), antibioticresponsive enteropathy (ARE) and inflammatory bowel disease (IBD) is possible by means of the response to a specific treatment. These disease forms are mostly difficult to differentiate clinically. Thus, it is the goal of various studies to establish biomarkers, whose purpose it is to increase the timely sensitivity of early diagnostics and prognostics of the disease. This prospective, singlecenter study examined, whether a simultaneous measurement of the biomarkers S100A12, calprotectin, C-reactive protein (CRP) and N-methylhistamine (NMH) in serum and/or faeces can improve the monitoring of canine chronic inflammatory enteropathies. Markers were to be identified, which could be of diagnostic and/or prognostic value, either alone or in combination. To this end, 32 dogs with chronic intermittent or persistent gastrointestinal symptoms presented from March 2015 to March 2018 at the Small Animal Clinic of the Freie Universität Berlin were included in this study. Data on their medical history, signalment, clinical disease activity (Canine Inflammatory Bowel Disease Activity Index (CIBDAI)), laboratory parameters as well as imaging diagnostics and endoscopy were analysed. Based on their response to a specific therapy, the animals were classified into the groups FRE (n= 11), ARE (n= 9) and IBD (n= 12). The measurement of the biomarkers ensued, whenever possible, at time of initial examination, followup and final presentation. The response to therapy or the improvement of symptoms were classified as clinical, partial or absent remission, respectively.
The data on the three diagnosis groups were compared. No significant differences between the diagnosis groups regarding medical history, signalment or symptoms were seen. The CIBDAI was significantly increased in the dogs with IBD compared to dogs with FRE or ARE (p= 0.015) at time of the initial examination. Dogs of the IBD-group achieved a complete clinical remission (p= 0.046) less often. A significant difference between the disease groups (p= 0.048) was also seen for calprotectin measured in serum. Dogs with IBD showed significantly increased calprotectin concentrations in serum compared to dogs with FRE or ARE. Based on this strong positive correlation between S100A12 and calprotectin in serum (rs = 0.810; p <0.0001), the sole measurement of calprotectin in serum seems sufficient. The faecal markers S100A12 and calprotectin showed the highest concentrations at initial examination in the FRE-group. During disease progression, both markers reached the highest concentrations in the IBD-group. Therefore, follow-up measurements of these markers could be indicative of the disease activity. As both markers also strongly correlated in faeces (rs = 0.934; p <0.0001), the measurement of one of these markers - calprotectin or S100A12 - in faeces seems sufficient. Moreover, the NMH measured in serum seems to facilitate a prognostic prediction regarding the response to therapy at initial examination. Dogs with partial or absent clinical remission showed significantly increased serum NMH concentrations (p= 0.007) compared to dogs with complete remission. Furthermore, dogs with IBD presented with increased faecal NMH-values, both at initial examination as well as at follow-up examinations, than dogs with FRE or ARE. Based on the findings of this study NMH in serum and faeces as well as serum Calprotectin appear to be beneficial when diagnosing chronic- inflammatory enteropathies in dogs.
The faecal markers seem to be indicative of a renewed clinical deterioration. Thus, the faecal biomarkers are best suited for follow-up examinations, while the serum biomarkers enable a prediction regarding diagnosis and prognosis at initial examination, or show the clinical activity during disease progression, respectively. The small study population constitutes the largest limitation of this study. Larger prospective studies should follow, to verify the ascertained correlations herein.