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Please click on one of the links below to find out more information
about what research is going on at North Carolina State University.
1. NCSU SCWT Colony
2. PLE/PLN
3. Mode of inheritance of PLE/PLN
4. Pathogenesis of PLE/PLN
1. NCSU SCWT Colony
We have a colony of dogs that were born to affected SCWT. We have 6
purebred SCWT (3 male, 3 female, born 7/94 and 2/95), 8 SCWT x beagle
(4 males, 4 females, born 10/96) and 4 inbred SCWT (1 male, 3 females,
born 7/97). We have evaluated all dogs in the colony at regular intervals
for clinical manifestations of PLE/PLN. All of the 6 purebred SCWT have
PLE, 2 definitely have PLN and another 2 may have PLN. All 4 inbred
SCWT have PLE. It is still too early to comment on the SCWT x beagle
dogs, although if the syndrome is found in these dogs, it is inherited
as a dominant trait.
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Pictured here are some of the SCWT in the North Carolina State
University colony. |
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2. PLE/PLN
The earliest abnormal finding in our 6 purebred SCWT was eosinophilia
(peripheral eosinophils > 750/µl) occurring in 6/6 dogs at
a median age of 6 months. Eosinophilia has persisted beyond 15 months
of age in 4/6 dogs. Fecal API concentration increased (>6 µg/g) in
6/6 dogs at a median age of 8 months; however, increases have been sporadic
in 5 dogs while persisting in only 1 female dog. Hypoglobulinemia (serum
globulin <2.5 g/dl) developed in 5/6 dogs at a median age of 23.5
months. Hypoalbuminemia (serum albumin < 2.5 g/dl) has occurred in
3 dogs at 19, 19 and 26 months of age. Questionable increases in urine
protein:creatinine ratios (>0.5) have occurred in 3 dogs at 12, 12,
and 15 months of age whereas definitive increases in urine protein:creatinine
ratios (>1.0) have occurred in only 2 dogs at 20 ad 22 months of
age. Evaluation of renal biopsy specimens revealed mild glomerular abnormalities
in 4 dogs at 12 months of age but definitive changes of glomerulonephritis
have been seen in only 1 dog at 24 months of age. The number of intestinal
mucosal eosinophils, as determined by morphometric analysis, was increased
in intestinal biopsy specimens obtained via gastroduodenoscopy as early
as 12 months of age in 6/6 dogs. This finding has been persistent in
5 dogs.
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3. Mode of inheritance of PLE/PLN
We do not yet know the mode of inheritance of PLE/PLN in SCWT. The
dogs of our colony will be used to make this determination.
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4. Pathogenesis of PLE/PLN
We hypothesize that food hypersensitivity reactions are involved in
the pathogenesis of PLE/PLN of SCWT. Our initial investigation of the
association of food hypersensitivities and PLE/PLN involved feeding
our original 6 affected SCWT gluten, a potential food allergen found
in wheat, for 6 weeks. The dogs were 17-24 months of age at the time
of the study and had only mild manifestations of the disease. There
was a relative increase in duodenal mucosal lymphocytes/plasma cells
and a significant decrease in serum globulin concentration after gluten
administration. However, there were no significant differences in fecal
API or serum albumin concentrations or urine protein:creatinine ratios
after gluten administration. Although gluten administration did evoke
some changes, the changes were mild.
To further evaluate for the presence of food hypersensitivity
reactions in affected dogs, we performed gastroscopic food sensitivity
testing (GFST) followed by oral challenge (provocation) in our 6 purebred
dogs. At the time of this study, the dogs were 28-39 months of age and
still had only mild clinical signs of disease. Extracts of corn, egg,
soybean, wheat, chicken, milk and lamb were used for GFST. Five of 6
dogs had definitive positive reactions: milk, 4; lamb, 2; wheat, 1;
chicken, 1. During oral challenge, dogs were given 7 test meals of chicken,
corn, cottage cheese, farina wheat, lamb, tofu, and lactose-free milk
over a 14 day period. Abnormal clinical signs (pruritus, vomiting, increased
fecal softness or increased defecation frequency) were observed during
oral challenge study in all 6 dogs: chicken, 5; corn, 5; tofu, 3; cottage
cheese, 2; milk, 2; farina wheat, 2; lamb, 2. Serum albumin was significantly
decreased and fecal API was significantly increased after oral challenge
but there were no differences in serum globulin concentrations or urine
protein:creatinine ratios. Although there was a high occurrence of reactions
to lamb and milk, none of the dogs have been given lamb or cow's milk
prior to the study.
Preliminary data supports that mast cell degranulation
responses are different between SCWT affected with PLE/PLN and control
dogs. Affected SCWT had significantly less histamine released per mast
cell from jejunal biopsies when cells were stimulated with concanavalin
A or IgE.
References:
Littman MP, Damback DM, Vaden SL, Giger U. Familial
protein-losing enteropathy and/or protein-losing nephropathy in soft-coated
wheaten terriers: 222 cases (1983-1997). J Vet Intern Med, 2000; 14:
68-80.
Vaden SL, Hammerberg B, Davenport DJ, Orton SM, Trogdon
MM, Melgarejo LT, VanCamp SD, Williams DA. Food hypersensitivity reactions
in soft coated wheaten terriers with protein losing enteropathy or protein-losing
nephropathy or both: gastroscopic food sensitivity testing, dietary
provocation and fecal immunoglobulin E. J Vet Intern Med, 2000; 14:
60-67.
Vaden SL, Sellon RK, Melgarejo LT, Williams DA, Trogdon
MM, VanCamp SD, Argenzio R. Evaluation of intestinal permeability and
gluten sensitivity in soft coated wheaten terriers with familial protein-losing
enteropathy, protein-losing nephropathy, or both. Amer J Vet Res, 2000,
61:518-524.
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