Page 666 - Clinical Small Animal Internal Medicine

634 Section 6 Gastrointestinal Disease

Perinuclear Antineutrophilic Cytoplasmic concentrations of calprotectin correlate very well with
VetBooks.ir Antibodies clinical disease activity in children with IBD.
An immunoassay for measurement of canine calpro-
Perinuclear antineutrophilic cytoplasmic antibodies
(pANCA) have been useful in the diagnosis of human tectin in serum and fecal samples is now available, and it
was shown that a serum calprotectin concentration of
IBD for decades. These antibodies are serum autoanti- ≥296.0 μg/L as a cut‐off had a sensitivity of 82.4% and
bodies similar to antinuclear antibodies (ANA), which specificity of 68.4% for distinguishing dogs with idio-
seem to be more specific for intestinal disease than ANA pathic IBD from healthy dogs. However, calprotectin
in dogs. They are detected by indirect immunofluores- concentrations were not significantly correlated with the
cence assays where a typical pattern of perinuclear stain- clinical severity, serum C‐reactive protein concentration,
ing of canine granulocytes can be seen. or severity of histopathologic changes. The clinical use-
In the first study which assessed the possible clinical
usefulness of pANCA in dogs with IBD, sensitivity for fulness of this test when used in serum or fecal samples
still needs to be confirmed in prospective studies.
pANCA was 0.51 and specificity ranged between 0.56
and 0.95. pANCA proved to be a highly specific marker
for CE in dogs when the group of dogs with chronic diar- Immunohistochemistry for P‐Glycoprotein
rhea of other causes were tested against the group of on Intestinal Biopsies
dogs with CE (specificity 0.95). This is in agreement with P‐glycoprotein (p‐gp) is a transmembrane protein func-
reports from human medicine that show a specificity of tioning as a drug‐efflux pump in the intestinal epithe-
up to 94% for pANCA when distinguishing between IBD lium. Human patients with IBD who fail to respond to
and healthy controls as well as patients with non‐IBD treatment with glucocorticosteroids express high levels
diarrhea. Furthermore, when pANCA were tested in a of p‐gp in lamina propria lymphocytes.
group of dogs with FRD versus SRD, a positive pANCA So far, two research groups have evaluated p‐gp expres-
titer was significantly associated with FRD. sion in biopsies of dogs with CE. In one study, duodenal
The pANCA assay could therefore provide valuable
help to the veterinarian presented with the clinical pic- biopsies from 48 dogs were evaluated by immunohisto-
chemistry. The dogs treated with prednisolone showed a
ture of a dog with chronic diarrhea and possible IBD. If significantly higher p‐gp expression in lamina propria
the result is positive, a food‐responsive chronic enter- lymphocytes after treatment compared with expression
opathy is highly likely, but if the result is negative, CE before treatment. In contrast, the group treated solely
cannot be excluded. with an elimination diet showed no difference in p‐gp
pANCA also seem to be associated with the syndrome
of familial protein‐losing enteropathy in soft‐coated scores before and after treatment. Moreover, a statisti-
cally significant association between refractoriness to
wheaten terriers (SCWTs). pANCA were detectable in steroid treatment and high p‐gp expression was found in
the serum of dogs on average 1–2 years before the onset the steroid treatment group. In another recent study, p‐
of clinical disease and were highly correlated with gp expression was compared between dogs with CE and
hypoalbuminemia. This test could serve as a useful healthy controls, and was found to be higher in duodenal
adjunct for this specific disease in SCWTs as an early epithelial cells of dogs with CE compared to control
screening test. dogs. These results indicate that epithelial and lamina
Care must be taken in interpreting a positive pANCA
test result if other inflammatory or immune‐mediated propria lymphocyte expression of p‐gp is upregulated in
dogs with CE, and they are even higher after predniso-
diseases are present in the dog. A recent study showed lone treatment. In addition, high p‐gp expression could
that many dogs with various vector‐borne diseases or indicate possible multidrug resistance and should be
immune‐mediated hemolytic anemia (IMHA) were pos- taken into account when dealing with dogs who have
itive for pANCA. Unfortunately, this test is not commer- failed steroid treatment before.
cially available yet, but could become one of the standard
tests for work‐up of CE in the future.
Genetic Testing

Calprotectin and S100A12 Over the last decade, numerous genes have been found
to be associated with an increased risk of development
Calprotectin and S100A12 are calcium‐binding proteins of IBD in human beings, many of them implicated in the
that are abundant in the granules of neutrophils and innate immune response in the intestine. In dogs, it has
macrophages. In people with IBD, serum and fecal con- always been obvious to clinicians that IBD could have a
centrations of these proteins have been found to be genetic component. This is particularly evident in breeds
increased compared to healthy people. In addition, fecal like the boxer, which is predisposed to granulomatous