ECVD Canine Allergy Videos Flashcards
Unusual AD distribution in WHWT
Caudal dorsum
(r/o fleas)
Unusual AD distribution in GSD
Lateral thighs, neck
(r/o sarcoptes)
Unusual AD distribution in Shar Pei
Generalized
Unusual clinic lesions of AD in boxer
Urticaria, otitis
Unusual clinic lesions of AD in Dalmations
Pruritus w/o lesions
Unusual clinic lesions of AD in GSD
Pruritus w/o lesions; increased pyotraumatic dermatitis
Unusual clinic lesions of AD in Golden Retriever
Increased pyotraumatic dermatitis
Unusual clinic lesions of AD in Labrador retriever
Increased pyotraumatic dermatitis; dry skin, interdigital furunculosis
Unusual clinic lesions of AD in Shar Pei
Pruritus without lesions; increased otitis
Unusual clinic lesions of AD in WHWT
Increased Malassezia dermatitis and seborrhea; decreased conjunctivitis
Breed of dog in Switzerland with very strong genetic likelihood of developing cAD
WHWT
(maternal)
T or F: If neither parent has cAD, 0% risk of developing cAD
False. But higher chance of cAD with 1 parent and highest chance with both parents
Test to see which pathways are involved in cAD, help you find candidate genes to evaluate for pathogenesis of cAD
mRNA microarray studies
(Change can be in pathway to REGULATE tissue change, rather than changes in the skin itself –> visually normal cAD skin is NOT the same as actually normal skin)
S100A8 gene as it relates to skin barrier
Pro-inflammatory molecule on the epidermal differentiation complex (EDC)
-Correlated with severity of cAD and TNFa
-EDC includes filaggrin, loricin, involucrin
Gene sets common to cAD, hAD, asthma (5)
1) Eosinophilic allergic responses
2) Monocyte chemotacic protein (MCP) cluster
3) IL-1 family cluster
4) IFN- inducible genes
5) Keratin genes
NAME THAT GENE
Pro-inflammatory molecule on the epidermal differentiation complex (EDC)
-Correlated with severity of cAD and TNFa
-EDC includes filaggrin, loricin, involucrin
S100A8
Founder effect
Explains regional differences in allergies
-If 1 allergic dog is the sire of many other dogs in 1 region, then they will be more likely to have cAD
T or F: Filaggrin mutations are associated with cAD in WHWT
False
(Roque et al 2009)
Mutation in cAD dogs across breeds, geography
TSLP receptor
“Hypothesis free” way to look at genomes between affected and unaffected (but related) dogs
Genome wide linkage studies
(GWAS does NOT need related dogs, but only can look at SNPs)
GWLS study with 90 WHWT: gene with highest linkage score to cAD
S100A8
(FLG not associated in whwt again)
Which breed had linkage of cAD with D Farinae IgE levels
WHWT
Which breed had association of cAD and Acarus, Tyrophagus IgE levels
Labradors
Gene associated with cAD in Golden Retrievers
Filaggrin
RAB3C
Gene associated with cAD in GSD
Plakophilin 2
Gene enhancers associated with a risk haplotype
Gene associated with cAD in WHWT
Cytochrome P450 26B1
Protein released by damaged epithelial cells– associated with cAD
TSLP receptor
Enzyme that modulates T-cell and B-cell antigen responses– associated with cAD
Protein tyrosine phosphatase
(PTPN22)
Gene that encodes for PAR (protease activated receptors)– associated with cAD
F2R
Genes associated with positive IDST (4)
CMA1 (mast cell chymase)
SAA-1 (soluble PRR, can bind HDM antigens)
SPINK5 (encodes for LEKTI, which inhibits kallikreins, which degrades corneodesmosomes)
S100A8 (DAMP)
Chromosome associated with high IgE in labrador retrievers
CFA5
Chromosome associated with high IgE in WHWT
CFA35
Environmental influences that INCREASE cAD (5)
1) Urban
2) Regular bathing
3) C-section
4) Household hygiene
5) HDM exposure
Environmental influences that DECREASE cAD (4)
1) Rural
2) Multi-animal household
3) Non-commercial food
4) Skin barrier protective diet
How do allergens get into the body to cause cAD?
1) Epicutaneous
2) Oral
3) Inhaled
True or False: it is possible that immunotherapy can work through nonallergic mechanisms
TRUE
Mannan conjugated DerP2 benefits in dogs that are sensitized to OTHER allergens (NOT HDM)
3 functional tests to assess allergen sensitization –> rarely used
1) Prausnitz-Kustner (PK) test
2) Lymphocyte stimulation test
3) Basophil degranulation test– quantifies amount of cell-bound IgE
True or False: There is a strong correlation between positive IgE tests and clinical pattern of allergy
FALSE. Positive IgE serum test does not actually correlate with seasonality/indoor/outdoor of disease clinically
Many dogs have positives to seasonal allergens, with no seasonality and vice versa
T or F: Seasonal timing matters when performing serum testing
TRUE
Serum IgE may only be present during flare season. Memory T cells are still there, but IgE is gone from serum –> false negatives
True or false: Non-related allergens will NOT cross-react
FALSE
Toxocara canis and D farinae
Sarcoptes and HDMs
(PPV of sarcoptes tests can be LOW in dogs sensitized to D farinae)
(Dogs that are sensitized to HDM appear positive to sarcoptes, but not other way around)
Why do we get false positives on serum allergy tests?
IgE may be present, but that version of IgE is non-rheogenic (cannot induce MC degranulation)
True or false: Cross-reactive carbohydrate determinants affect IDST
FALSE. But they do affect serum tests.
–> more false positives, decreased specificity on serum tests.
–> CCD-blockers incubation before ELISA test can reduce false positive responses
-Allergen-associated cross-reacting glycoproteins
-Cannot bind to mast-cell-bound IgE
-Not of clinical significance EXCEPT alpha-galactose (tick allergen with red meat cross reactivity)
Which allergens have more CCD against them
Pollens. Weed, grass, tree
> > > dust mite, flea allergens
Which 2 medications were found to decrease serum IgE to allergens compared to untreated dogs? (Canning et al 2021)
Cyclosporine, Lokivetmab
We may need to re-think withdrawing medication prior to serum testing, as they may actually affect outcomes
T or F: Atopic dogs without malassezia hypersensitivity still have higher levels of IgE to Malassezia than non-atopic dogs
True
Does Staphylcoccal hypersensitivity exist?
Probably. Some dogs have higher levels of anti-Stapylococcal IgE than healthy dogs.
Tim Nuttal thinks this is similar to Malassezia hypersensitivity
Which type of infection does CAFR have an increased prevalence of?
Malassezia
T or F: there are cross reactions between pork and ruminants
TRUE
T or F: there are cross reactions between soy and grains
TRUE
Which version of food processing can result in REDUCED IgE binding (so less CAFR)
Cooked foods, wet foods –> denatures epitope
Higher IgE with high temp dry processing!! Can lead to glycosylation of proteins, forming glycoproteins, which are more allergenic than regular proteins
Raw also has high IgE binding
*Not published but super interesting
Protein contact dermatitis
Type I and IV sensitivity
Skin lesions in areas that make contact with allergy –> develop a few hours after exposure to allergen
Contact sensitivity to a protein (plant or animal protein), rather than to a chemical
Serology negative
Patch test positive
Skin barrier defects in cAD (6)
1) Increased TEWL
2) Abnormal keratinocyte morphology
3) Abnormal filaggrin expression
4) Abnormal lipid metabolism
5) Abnormal lipid lamellae
6) Abnormal ceramide profiles
Essential fatty acid metabolism
-Promote fewer inflammatory eicosinoids (LTB4, PGE2)
-Help promote healthier lipid layer in skin
T or F: atopic dogs have an altered lipid profile in NONLESIONAL skin of ceramides, sphingomyelins, acylcarnitines
True
Different from healthy skin, different from lesional atopic skin
T or F: changes in lipid profile with treatment with lokivetmab or oclacitinib
TRUE
BUT did not correlate with improved clinical outcome
Inflammatory signals released by keratinocytes (6)
1) ICAM-1
2) MHC class II
3) TARC
4) TNFalpha
5) IL-8
6) TSLP
How does the microbiome affect the skin barrier? (3)
Healthy bacteria are associated with:
1) Increased ceramides
2) Decreased TEWL
3) Decreased SCORFAD
Effect of topical emollients on skin microbiome
Recovers a more diverse microbiome
(human study)
Bathing’s impact on skin barrier
-TEWL increased after baths
-Also emollient only baths (no chx, miconazole) still decreased Malassezia population
Don’t overbath healthy dogs
Cytokines upregulated in ACUTE inflammation (Olivry 2016 transcriptomics study)
IL-31
IL-13 RA2 (receptor)
NGF
ALOX5, LTA4 (leukotriene)
Histamine
IL-6
IL-4
IL-33 (weird this is increased but TSLP is decreased??)
DOWN regulation of TSLP!!
When is IL-31 expressed in acute inflammation?
Expressed EARLY AND TRANSIENT (in skin)— but not realistic, because you will probably have more persistent exposure to allergen
Levels peak at 24-48 hours. Cytopoint should work within 24 hours
Increase in expression of IL-31RA on keratinocytes and nerves
Higher level in BLOOD, very transient in the skin
T or F: IL-31 levels correlate well with skin lesions
FALSE
No correlation based on Mochizuki + Olivry study 2021
What causes different versions of the IL-31 receptor?
3 variants of IL-31 receptor based on SPLICING
2 long variants- functional
1 short variant- nonfunctional
Which form of IL-31 RA is present in HEALTHY skin?
The SHORT (nonfunctional form!)
Which form of IL-31 RA is present in CHRONICALLY inflamed skin
Downregulation of BOTH long and short variants of IL-31 RA
BUT there is an INCREASE in IL-31 itself in chronically inflamed skin
Other than pruritus, what are 3 other roles of IL-31?
-Involved in acute inflammation
-Epidermal thinning
-Altered skin barrier
Changes to the IL-31 RA structure can result in increase in _______ activity, which may induce CHRONIC inflammatory patterns
Oncostatin-M
Which circulating inflammatory markers are elevated in cAD? (5)
-IL-17
-IL-31
-Total IgE
-Neutrophils
-Eosinophils
(A different study showed variation in IL-17, IL-22, and IL-31 expression)
Which 3 inflammatory response types are markers of acute atopic inflammation
Th2
Th17
Th22
Which cell makes a lot of TSLP
Keratinocytes
Which cell does TSLP act on
Activates Langerhans cells and T cells
Which type of inflammation does TSLP promote
Th2 differentiation
mutation in TSLP R associated with cAD
Which cytokines does TSLP induce production of
IL-4
IL-13
How much TSLP is present in nonlesional atopic skin compared to healthy skin
Significantly more TSLP in atopic skin, even if nonlesional
In CHRONIC cAD, in addition to Th2 cytokine increase, what other types of cytokines are increased?
Th1 (IFNgamma, TNFalpha)
Also Th22, Th17
TNFalpha levels in LESIONAL chronic cAD skin correlates with ______
Severity of disease
Which breed had a distinct cytokine profile for their cAD, compared to other breeds of atopic dogs
Staffordshire bull terriers (Mazrier et al 2021)
T or F: Altered levels of CXCL8, IL-7, IL-15, SCF/c-kit, GM-CSF are present in CAD skin +/- plasma
True
*CXCL8: neutrophil chemoattractant
*IL-7: B cell, T cell, NK development
*IL-15: promotes T cells
*SCF: mast cell growth and activation factor
* GM-CSF: promotes macrophages, dendritic cells, neutrophils/eosinophils, lymphocytes, platelets
Increases in IL-10 and FoxP3+ cells indicate ________ (success or failure) of ASIT
Success
IL-10 has been increased in _____ form of ASIT, but not ______ or _______
(SCIT, SLIT, ILIT)
IL-10 only found to be increased in ILIT in 1 study (Martini et al 2021)
Variable things seen in different papers
Lower levels of _______ cells at an early age was associated with a higher risk of cAD at an older age in WHWT
TReg cells
Which cells are increased in cAD, with a weak correlation with disease severity?
CD4+/CD25+/FOXP3+ TReg cells
(per Nuttal’s ECVD lecture)
T or F: TReg levels DECLINE in dogs with cAD over time
FALSE
This does happen in normal dogs. But TReg levels seem to be increased in cAD later on. However, low levels of TReg as a young dog is associated with cAD later in life
In addition to IL-31, what are other itch signaling molecules? (7)
1) Histamine
2) PAR2
3) TRPM8- menthol
4) TRPV1- capsaicin
5) Cannabinoid receptors
6) Opiod receptors
7) Substance P- NK1 & GABA
Lower levels of _______ cells at an early age was associated with a higher risk of cAD at an older age in WHWT
TReg cells
What happens to the diversity of microorganisms on cAD skin?
Decreased diversity
Skewed to Staphylococcus
Which of the below has the largest influences on skin microbiome?
-Household
-Sex
-Health
-Body site
Household had the largest influence on skin microbiome composition!
Result of Clavamox treatment on microbiome population
Reduces Staphylococcal population, but allows other bacteria to flourish –> restores microbiome diversity
What allows atopic children to have a more diverse microbiome during an atopic flare?
Proactive treatment, rather than just reactive treatment during a flare
Which immune cell helps regulate skin barrier and tolerance?
ILCs
ILC respond to TSLP, IL-33, IL-25 from keratinocytes and microbial alarm signals –> activate Th2 inflammation, degrade the skin barrier
In addition to skin microbiome, which other microbiome can affect skin health?
Gut microbiome
Gut dysbiosis is associated with human asthma and eczema
Protective or Susceptibility to cAD: antibiotic use
Susceptibility
Protective or Susceptibility to cAD: probiotics, macrobiotic diet
Protective
Protective or Susceptibility to cAD: Endotoxins
Protective
Biodiversity hypothesis
Modern version of hygiene hypothesis
Loss of macrodiversity in the environment and microdiversity within an individual leads to –>
1) Microbe dysbiosis
2) Immune dysfunction
3) Inflammatory dysresponse, lack of tolerance
4) Clinical symptoms of AD
T or F: Probiotics can potentially ameliorate progression of cAD
True
One study when giving probiotics to mother, affecting her puppies (Marsella)
Another study showed increased lesion scores, pruritus, and TEWL. BUT not change in microbiome (Santoro)
