Atopic dermatitis in West Highland white terriers - Part III: early life peripheral blood regulatory T cells are reduced in atopic dermatitis.

BACKGROUND: Regulatory T (Treg) cells are involved in homeostasis of immune regulation and suppression of inflammation and T-cell polarisation. Current knowledge regarding the role of Treg cells in the initiation of allergic disease is limited for both people and dogs. OBJECTIVES: To explore the role of circulating Treg cells and their possible influencing factors, on the development of atopic dermatitis (AD). METHODS AND MATERIALS: This study followed part of a birth cohort of West Highland white terrier dogs and classified them according to eventual clinical signs of AD (i.e. allergic versus healthy). The Treg phenotypes were assessed longitudinally by flow cytometry at 3, 3-12 and 12-36 months of age, and associated with development of AD. Different early life antigenic factors [endotoxins and allergens in house dust, Toxocara canis-specific immunoglobulin (Ig)E/IgG, allergen-specific and total IgE, skin microbiota] were measured at three months of age, and a possible association with Treg cell levels was assessed. RESULTS: The percentages of CD4+ CD25+ Foxp3+ Treg cells in healthy dogs were significantly higher at in 3-month-old (mean 4.5% healthy versus 3.3% allergic; P = 0.021) and <1-year-old (4.0% healthy versus 2.9% allergic; P = 0.028) dogs when compared to percentages of Treg cells in dogs that developed AD. There was a significantly positive correlation between the relative abundance of Lachnospiraceae on the skin and CD4+ CD25+ Foxp3+ Treg cells in puppies that became allergic (r = 0.568, P = 0.017). CONCLUSION AND CLINICAL IMPORTANCE: Further large-scale studies are needed to identify the practical value of these findings in AD diagnosis, treatment and prevention.

Atopic dermatitis in a cohort of West Highland white terriers in Switzerland. Part II: estimates of early life factors and heritability.

BACKGROUND: There is accumulating evidence in studies of allergic diseases in humans and dogs that environmental experiences during the first months of life can influence the development of allergic disease. No prospective study has evaluated this in veterinary medicine. HYPOTHESIS/OBJECTIVES: To assess early-life risk factors for canine atopic dermatitis (cAD) and estimate its heritability. ANIMALS: A West Highland white terrier birth cohort (n = 107) followed up to three years of age recording the development of cAD. METHODS AND MATERIALS: The effect of environmental factors [house dust mites (HDM), hygiene, feeding, lifestyle] and early-life determinants [breeder, mode of delivery, birth season, sex, litter size, early-life immunoglobulin E (IgE) levels] were assessed, using Stata SE 15.1 statistical analysis. Heritabilities were estimated using the R program packages MCMCglmm and QGglmm. RESULTS: Maternal allergic status [P = 0.013, odds ratio (OR 3.3)], male sex (P = 0.06), mode of delivery (P = 0.12), breeder (P = 0.06), presence of HDM (P = 0.11) and environmental hygiene level (P = 0.15) were identified as possible influence factors by bivariate analyses. In the multivariate analysis the male sex was significantly associated with the development of cAD in the offspring (P = 0.03, OR 2.4). The heritabilities on the observed scale were 0.31 (direct), 0.04 (maternal genetic effects) and 0.03 (maternal permanent environmental effects). CONCLUSION AND CLINICAL IMPORTANCE: These results suggest that several environmental factors could influence the development of cAD but clearly demonstrate the genetic influence of the individual and the dam. Further studies are needed to identify specific environmental factors, which could be potential targets for primary disease intervention.

Atopic dermatitis in West Highland white terriers - part I: natural history of atopic dermatitis in the first three years of life.

BACKGROUND: Canine atopic dermatitis (cAD) is a common allergic skin disease that is known to affect individuals early in life; the natural history of its initial development has not been documented. Some breeds such as West Highland white terriers (WHWTs) are highly predisposed to cAD. OBJECTIVES: To follow 100 WHWT puppies during their first three years and to record the onset of clinical signs of cAD. ANIMALS: One hundred and eight puppies from 29 litters were included and 90 were followed for three years. METHODS AND MATERIALS: Puppies were examined initially while with their breeders. After adoption, the owners were contacted twice each year and dogs were examined by veterinarians if signs compatible with cAD were detected; diagnosis of cAD was by two different definitions. The onset, location of the clinical signs and severity of cAD, as well as co-morbidities were recorded. RESULTS: The prevalence of cAD in the cohort was 52%. Most affected dogs (60%) developed signs of cAD during their first year of life and males were over-represented. The location of clinical signs mirrored those of previous descriptions. The severity of cAD was mild in 36% and severe in 13% of affected WHWTs. Dogs with cAD often exhibited other atopic diseases, but only gastro-intestinal signs were significantly different between WHWTs with and without cAD. Adverse reaction to foods was diagnosed in 24% of dogs. CONCLUSION AND CLINICAL IMPORTANCE: This longitudinal study of puppies from a predisposed breed sheds new light on the early development of cAD in WHWTs.

A pilot study of total and allergen-specific IgE serum levels during anestrous, estrous and pregnancy in healthy female dogs.

BACKGROUND: Allergen-specific IgE serology is used for the determination of sensitization status in dogs with atopic dermatitis; the influence of the female reproductive cycle on the results of such methods has not been studied in dogs. OBJECTIVES: To compare the total and allergen-specific IgE of healthy bitches during anestrous, estrous and pregnancy. ANIMALS: Eight privately owned, healthy bitches. METHODS: Total and allergen-specific IgE levels were determined in eight bitches at three different time-points of their reproductive cycle: anestrous, estrous and pregnancy. RESULTS: Total IgE was significantly decreased (median: 74%) in female dogs during pregnancy when compared to anestrous. In 14 of 216 (6%), allergen-specific IgE test results were variably positive and negative at different stages of the reproductive cycle. This variation, however, was not related to changes in total serum IgE levels. CONCLUSIONS: Total IgE serum levels are reduced during pregnancy in female dogs. However, results of one allergen-specific IgE test did not appear to be markedly altered by the reproductive cycle in healthy bitches.

Total and Toxocara canis larval excretory/secretory antigen- and allergen-specific IgE in atopic and non-atopic dogs.

BACKGROUND: Total IgE concentrations are higher in dogs than in humans. Persistent Toxocara canis larval infection is prevalent in dogs and is associated with substantial specific antibody reactions. A correlation, however, between total IgE and T. canis-specific antibody levels in dogs has not been evaluated. OBJECTIVES: To determine the relationship between total IgE, T. canis-specific IgG and IgE, and allergen-specific IgE levels in atopic and non-atopic dogs, and to evaluate possible confounding factors. ANIMALS: Sera of 30 atopic and 30 non-atopic client-owned dogs. METHODS: Total IgE, T. canis-specific antibody and allergen-specific IgE levels were evaluated by ELISA. RESULTS: Total IgE, T. canis-specific antibody and allergen-specific IgE levels were significantly higher in non-atopic compared to atopic dogs. A positive correlation was demonstrated between T. canis-specific IgG and T. canis-specific IgE; T. canis-specific IgG and total IgE; T. canis-specific IgE and total IgE; and allergen-specific IgE and total IgE. No differences were detected on the basis of age, gender, vaccination status; deworming or season between atopic and non-atopic dogs. Previous immunomodulatory treatment and cause of atopy did not influence antibody levels of atopic dogs. CONCLUSIONS: Toxocara canis-specific IgE appears to be a major component of total IgE in dogs. Total and T. canis-specific IgE levels are higher in non-atopic compared to atopic dogs. It is speculated that T. canis infection may have a protective effect against the development of canine atopic dermatitis and/or that elevations in total serum IgE level are often not associated with atopic dermatitis.