Canine atopic dermatitis – what have we learned?

Nuttall, Tim; Uri, Maarja; Halliwell, R.E.W.

doi:10.1136/vr.f1134

Cited by 31 publications

(33 citation statements)

References 87 publications

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“…Yet, they are present also in many other tissues, like the heart, brain, kidneys and joints [8,9]. Once activated by either IgE-dependent or IgE-independent, MCs degranulate, a process that results in the exocytosis of an impressive array of pro-inflammatory and immuno-regulatory mediators that initiate immediate phase inflammatory responses and late phase reactions [10,11]. Particularly, MCs release Th2 polarizing cytokines such as IL4, IL10, and IL13 which can induce a stimulated naive CD4+ T cell to become a Th2 cell when activated in the lymph node [12].…”

Section: Introductionmentioning

confidence: 99%

Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis

Abramo

Campora

Albanese³

et al. 2014

BMC Vet Res

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BackgroundDespite the precise pathogenesis of atopic dermatitis (AD) is unknown, an immune dysregulation that causes Th2-predominant inflammation and an intrinsic defect in skin barrier function are currently the two major hypotheses, according to the so-called outside-inside-outside model. Mast cells (MCs) are involved in AD both by releasing Th2 polarizing cytokines and generating pruritus symptoms through release of histamine and tryptase. A link between MCs and skin barrier defects was recently uncovered, with histamine being found to profoundly contribute to the skin barrier defects.Palmitoylethanolamide and related lipid mediators are endogenous bioactive compounds, considered to play a protective homeostatic role in many tissues: evidence collected so far shows that the anti-inflammatory effect of palmitoylethanolamide depends on the down-modulation of MC degranulation.Based on this background, the purpose of the present study was twofold: (a) to determine if the endogenous levels of palmitoylethanolamide and other bioactive lipid mediators are changed in the skin of AD dogs compared to healthy animals; (b) to examine if MC number is increased in the skin of AD dogs and, if so, whether it depends on MC in-situ proliferation.ResultsThe amount of lipid extract expressed as percent of biopsy tissue weight was significantly reduced in AD skin while the levels of all analyzed bioactive lipid mediators were significantly elevated, with palmitoylethanolamide showing the highest increase.In dogs with AD, the number of MCs was significantly increased in both the subepidermal and the perifollicular compartments and their granule content was significantly decreased in the latter. Also, in situ proliferation of MCs was documented.ConclusionsThe levels of palmitoylethanolamide and other bioactive lipid mediators were shown to increase in AD skin compared to healthy samples, leading to the hypothesis that they may be part of the body’s innate mechanisms to maintain cellular homeostasis when faced with AD-related inflammation. In particular, the increase may be considered a temptative response to down-regulating the observed elevation in the number, functionality and proliferative state of MCs in the skin of AD dogs. Further studies are warranted to confirm the hypothesis.

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Section: Introductionmentioning

confidence: 99%

Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis

Abramo

Campora

Albanese³

et al. 2014

BMC Vet Res

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“…IMPA is a type III autoimmune disease in which antigen-antibody complexes accumulate in the joint space and lead to ongoing inflammation (Johnson and Mackin 2012). AD is an allergic syndrome caused by an aberrant immune response to an environmental exposure (Olivry et al 2010; Nuttall et al 2013). This suggests that DLA-79*001:02 may play a role in functions that are common across these diseases such as pathways which perpetuate an exuberant immune response.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs

et al. 2015

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Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher’s exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12), and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared to the reference allele, DLA-79*001:01) resulting in F33L and N37D amino acid changes. These mutations occur in the peptide binding pocket of the protein, and based upon our computational modeling studies are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly, and to determine the specific mechanism by which the identified variants alter canine immune system function.

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“…Canine atopic dermatitis (CAD) is a common, genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features [1,2], having a prevalence of 20-30% [3]. In terms of origin, this disease is complex and multifactorial and involves genetic factors [4,5], immune dysregulation, allergic sensitization, skin barrier defects, cutaneous microbiome, and environmental factors [6][7][8]. The pathogenesis of canine and human atopic dermatitis is not fully understood [9].…”

Section: Introductionmentioning

confidence: 99%

Multidose intramuscular allogeneic adipose stem cells decrease the severity of canine atopic dermatitis: A pilot study

Enciso

Amiel-Pérez

Pando³

et al. 2019

Vet World

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Aim:The aim of this pilot study was to evaluate the therapeutic and safety performance of an intramuscular treatment protocol of multidose of allogeneic adipose stem cells (ASCs) isolated, characterized, and expanded ex vivo from a healthy canine donor. Materials and Methods:Twelve dogs diagnosed with canine atopic dermatitis (CAD) were intramuscularly treated with 0.5×10 6 of cryopreserved ASCs from a healthy immunized young canine Ehrlichia canis free donor weekly for 6 weeks. Treatment efficacy was evaluated by the pruritus index and the CAD Lesion Index (CADLI) test. Safety and adverse effects were determined by injection site reaction, weight, blood chemistry, liver function, and whole blood count.Results: Canine ASCs obtained from a donor met the minimum qualities required for this type of cells and showed viability of 90% after thawing. The efficacy of the CADLI score and the pruritus index in 12 dogs with atopic dermatitis was statistically significant efficacy. No adverse reactions were observed at the intramuscular application site, or in relation to animal weight, blood cell populations, or liver and renal function. Conclusion:These results suggest that intramuscular administration of cryopreserved ASCs to dogs with atopic dermatitis is a promising cellular therapeutic product for the relief of the symptoms of this disease; however, the duration of the effects obtained with this dose and with other doses should be evaluated, as well as possible immune reactions. As far as we know, this is the first report of the use of multiple intramuscular doses cryopreserved ASCs to treat atopic dermatitis.

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Canine atopic dermatitis – what have we learned?

Cited by 31 publications

References 87 publications

Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis

Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis

Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs

Multidose intramuscular allogeneic adipose stem cells decrease the severity of canine atopic dermatitis: A pilot study

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