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EV ACVD Study > ECVD Canine Allergy Videos > Flashcards

ECVD Canine Allergy Videos Flashcards

1
Q

Unusual AD distribution in WHWT

A

Caudal dorsum
(r/o fleas)

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2
Q

Unusual AD distribution in GSD

A

Lateral thighs, neck
(r/o sarcoptes)

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3
Q

Unusual AD distribution in Shar Pei

A

Generalized

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4
Q

Unusual clinic lesions of AD in boxer

A

Urticaria, otitis

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5
Q

Unusual clinic lesions of AD in Dalmations

A

Decreased pruritus w/o lesions

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6
Q

Unusual clinic lesions of AD in GSD

A

Decreased pruritus w/o lesions; increased pyotraumatic dermatitis

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7
Q

Unusual clinic lesions of AD in Golden Retriever

A

Increased pyotraumatic dermatitis

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8
Q

Unusual clinic lesions of AD in Labrador retriever

A

Increased pyotraumatic dermatitis; dry skin, interdigital furunculosis

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9
Q

Unusual clinic lesions of AD in Shar Pei

A

Decreased pruritus without lesions; increased otitis

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10
Q

Unusual clinic lesions of AD in WHWT

A

Increased Malassezia dermatitis and seborrhea; decreased conjunctivitis

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11
Q

Breed of dog in Switzerland with very strong genetic likelihood of developing cAD

A

WHWT
(maternal)

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12
Q

T or F: If neither parent has cAD, 0% risk of developing cAD

A

False. But higher chance of cAD with 1 parent and highest chance with both parents

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13
Q

Test to see which pathways are involved in cAD, help you find candidate genes to evaluate for pathogenesis of cAD

A

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)

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14
Q

S100A8 gene as it relates to skin barrier

A

Pro-inflammatory molecule on the epidermal differentiation complex (EDC)
-Correlated with severity of cAD and TNFa
-EDC includes filaggrin, loricin, involucrin

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15
Q

Gene sets common to cAD, hAD, asthma (5)

A

1) Eosinophilic allergic responses
2) Monocyte chemotacic protein (MCP) cluster
3) IL-1 family cluster
4) IFN- inducible genes
5) Keratin genes

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16
Q

NAME THAT GENE

Pro-inflammatory molecule on the epidermal differentiation complex (EDC)
-Correlated with severity of cAD and TNFa
-EDC includes filaggrin, loricin, involucrin

A

S100A8

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17
Q

Founder effect

A

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

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18
Q

T or F: Filaggrin mutations are associated with cAD in WHWT

A

False
(Roque et al 2009)

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19
Q

Mutation in cAD dogs across breeds, geography

A

TSLP receptor

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20
Q

“Hypothesis free” way to look at genomes between affected and unaffected (but related) dogs

A

Genome wide linkage studies

(GWAS does NOT need related dogs, but only can look at SNPs)

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21
Q

GWLS study with 90 WHWT: gene with highest linkage score to cAD

A

S100A8

(FLG not associated in whwt again)

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22
Q

Which breed had linkage of cAD with D Farinae IgE levels

A

WHWT

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23
Q

Which breed had association of cAD and Acarus, Tyrophagus IgE levels

A

Labradors

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24
Q

Gene associated with cAD in Golden Retrievers

A

Filaggrin
RAB3C

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25
Q

Gene associated with cAD in GSD

A

Plakophilin 2
Gene enhancers associated with a risk haplotype

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26
Q

Gene associated with cAD in WHWT

A

Cytochrome P450 26B1

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27
Q

Protein released by damaged epithelial cells– associated with cAD

A

TSLP receptor

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28
Q

Enzyme that modulates T-cell and B-cell antigen responses– associated with cAD

A

Protein tyrosine phosphatase
(PTPN22)

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29
Q

Gene that encodes for PAR (protease activated receptors)– associated with cAD

A

F2R

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30
Q

Genes associated with positive IDST (4)

A

CMA1 (mast cell chymase)
SAA-1 (soluble PRR, can bind HDM antigens)
SPINK5 (encodes for LEKTI, which inhibits kallikreins, which degrades corneodesmosomes)
S100A8 (DAMP)

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31
Q

Chromosome associated with high IgE in labrador retrievers

A

CFA5

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32
Q

Chromosome associated with high IgE in WHWT

A

CFA35

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33
Q

Environmental influences that INCREASE cAD (5)

A

1) Urban
2) Regular bathing
3) C-section
4) Household hygiene
5) HDM exposure

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34
Q

Environmental influences that DECREASE cAD (4)

A

1) Rural
2) Multi-animal household
3) Non-commercial food
4) Skin barrier protective diet

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35
Q

How do allergens get into the body to cause cAD?

A

1) Epicutaneous
2) Oral
3) Inhaled

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36
Q

True or False: it is possible that immunotherapy can work through nonallergic mechanisms

A

TRUE

Mannan conjugated DerP2 benefits in dogs that are sensitized to OTHER allergens (NOT HDM)

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37
Q

3 functional tests to assess allergen sensitization –> rarely used

A

1) Prausnitz-Kustner (PK) test
2) Lymphocyte stimulation test
3) Basophil degranulation test– quantifies amount of cell-bound IgE

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38
Q

True or False: There is a strong correlation between positive IgE tests and clinical pattern of allergy

A

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

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39
Q

T or F: Seasonal timing matters when performing serum testing

A

TRUE

Serum IgE may only be present during flare season. Memory T cells are still there, but IgE is gone from serum –> false negatives

40
Q

True or false: Non-related allergens will NOT cross-react

A

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)

41
Q

Why do we get false positives on serum allergy tests?

A

IgE may be present, but that version of IgE is non-rheogenic (cannot induce MC degranulation)

42
Q

True or false: Cross-reactive carbohydrate determinants affect IDST

A

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)

43
Q

Which allergens have more CCD against them

A

Pollens. Weed, grass, tree

> > > dust mite, flea allergens

44
Q

Which 2 medications were found to decrease serum IgE to allergens compared to untreated dogs? (Canning et al 2021)

A

Cyclosporine, Lokivetmab

We may need to re-think withdrawing medication prior to serum testing, as they may actually affect outcomes

45
Q

T or F: Atopic dogs without malassezia hypersensitivity still have higher levels of IgE to Malassezia than non-atopic dogs

A

True

46
Q

Does Staphylcoccal hypersensitivity exist?

A

Probably. Some dogs have higher levels of anti-Stapylococcal IgE than healthy dogs.

Tim Nuttal thinks this is similar to Malassezia hypersensitivity

47
Q

Which type of infection does CAFR have an increased prevalence of?

A

Malassezia

48
Q

T or F: there are cross reactions between pork and ruminants

A

TRUE

49
Q

T or F: there are cross reactions between soy and grains

A

TRUE

50
Q

Which version of food processing can result in REDUCED IgE binding (so less CAFR)

A

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

51
Q

Protein contact dermatitis

A

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

52
Q

Skin barrier defects in cAD (6)

A

1) Increased TEWL
2) Abnormal keratinocyte morphology
3) Abnormal filaggrin expression
4) Abnormal lipid metabolism
5) Abnormal lipid lamellae
6) Abnormal ceramide profiles

53
Q

Essential fatty acid metabolism

A

-Promote fewer inflammatory eicosinoids (LTB4, PGE2)
-Help promote healthier lipid layer in skin

54
Q

T or F: atopic dogs have an altered lipid profile in NONLESIONAL skin of ceramides, sphingomyelins, acylcarnitines

A

True

Different from healthy skin, different from lesional atopic skin

55
Q

T or F: changes in lipid profile with treatment with lokivetmab or oclacitinib

A

TRUE

BUT did not correlate with improved clinical outcome

56
Q

Inflammatory signals released by keratinocytes (6)

A

1) ICAM-1
2) MHC class II
3) TARC
4) TNFalpha
5) IL-8
6) TSLP

57
Q

How does the microbiome affect the skin barrier? (3)

A

Healthy bacteria are associated with:
1) Increased ceramides
2) Decreased TEWL
3) Decreased SCORFAD

58
Q

Effect of topical emollients on skin microbiome

A

Recovers a more diverse microbiome
(human study)

59
Q

Bathing’s impact on skin barrier

A

-TEWL increased after baths

-Also emollient only baths (no chx, miconazole) still decreased Malassezia population

Don’t overbath healthy dogs

60
Q

Cytokines upregulated in ACUTE inflammation (Olivry 2016 transcriptomics study)

A

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!!

61
Q

When is IL-31 expressed in acute inflammation?

A

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

62
Q

T or F: IL-31 levels correlate well with skin lesions

A

FALSE
No correlation based on Mochizuki + Olivry study 2021

63
Q

What causes different versions of the IL-31 receptor?

A

3 variants of IL-31 receptor based on SPLICING
2 long variants- nonfunctional
1 short variant- nonfunctional

64
Q

Which form of IL-31 RA is present in HEALTHY skin?

A

The SHORT (nonfunctional form!)

65
Q

Which form of IL-31 RA is present in CHRONICALLY inflamed skin

A

Downregulation of BOTH long and short variants of IL-31 RA

BUT there is an INCREASE in IL-31 itself in chronically inflamed skin

66
Q

Other than pruritus, what are 3 other roles of IL-31?

A

-Involved in acute inflammation
-Epidermal thinning
-Altered skin barrier

67
Q

Changes to the IL-31 RA structure can result in increase in _______ activity, which may induce CHRONIC inflammatory patterns

A

Oncostatin-M

68
Q

Which circulating inflammatory markers are elevated in cAD? (5)

A

-IL-17
-IL-31
-Total IgE
-Neutrophils
-Eosinophils

(A different study showed variation in IL-17, IL-22, and IL-31 expression)

69
Q

Which 3 inflammatory response types are markers of acute atopic inflammation

A

Th2
Th17
Th22

70
Q

Which cell makes a lot of TSLP

A

Keratinocytes

71
Q

Which cell does TSLP act on

A

Activates Langerhans cells and T cells

72
Q

Which type of inflammation does TSLP promote

A

Th2 differentiation

mutation in TSLP R associated with cAD

73
Q

Which cytokines does TSLP induce production of

A

IL-4
IL-13

74
Q

How much TSLP is present in nonlesional atopic skin compared to healthy skin

A

Significantly more TSLP in atopic skin, even if nonlesional

75
Q

In CHRONIC cAD, in addition to Th2 cytokine increase, what other types of cytokines are increased?

A

Th1 (IFNgamma, TNFalpha)

Also Th22, Th17

76
Q

TNFalpha levels in LESIONAL chronic cAD skin correlates with ______

A

Severity of disease

77
Q

Which breed had a distinct cytokine profile for their cAD, compared to other breeds of atopic dogs

A

Staffordshire bull terriers (Mazrier et al 2021)

78
Q

T or F: Altered levels of CXCL8, IL-7, IL-15, SCF/c-kit, GM-CSF are present in CAD skin +/- plasma

A

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

79
Q

Increases in IL-10 and FoxP3+ cells indicate ________ (success or failure) of ASIT

A

Success

80
Q

IL-10 has been increased in _____ form of ASIT, but not ______ or _______
(SCIT, SLIT, ILIT)

A

IL-10 only found to be increased in ILIT in 1 study (Martini et al 2021)

Variable things seen in different papers

81
Q

Lower levels of _______ cells at an early age was associated with a higher risk of cAD at an older age in WHWT

A

TReg cells

82
Q

Which cells are increased in cAD, with a weak correlation with disease severity?

A

CD4+/CD25+/FOXP3+ TReg cells
(per Nuttal’s ECVD lecture)

83
Q

T or F: TReg levels DECLINE in dogs with cAD over time

A

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

84
Q

In addition to IL-31, what are other itch signaling molecules? (7)

A

1) Histamine
2) PAR2
3) TRPM8- menthol
4) TRPV1- capsaicin
5) Cannabinoid receptors
6) Opiod receptors
7) Substance P- NK1 & GABA

85
Q

Lower levels of _______ cells at an early age was associated with a higher risk of cAD at an older age in WHWT

A

TReg cells

86
Q

What happens to the diversity of microorganisms on cAD skin?

A

Decreased diversity

Skewed to Staphylococcus

87
Q

Which of the below has the largest influences on skin microbiome?

-Household
-Sex
-Health
-Body site

A

Household had the largest influence on skin microbiome composition!

88
Q

Result of Clavamox treatment on microbiome population

A

Reduces Staphylococcal population, but allows other bacteria to flourish –> restores microbiome diversity

89
Q

What allows atopic children to have a more diverse microbiome during an atopic flare?

A

Proactive treatment, rather than just reactive treatment during a flare

90
Q

Which immune cell helps regulate skin barrier and tolerance?

A

ILCs

ILC respond to TSLP, IL-33, IL-25 from keratinocytes and microbial alarm signals –> activate Th2 inflammation, degrade the skin barrier

91
Q

In addition to skin microbiome, which other microbiome can affect skin health?

A

Gut microbiome

Gut dysbiosis is associated with human asthma and eczema

92
Q

Protective or Susceptibility to cAD: antibiotic use

A

Susceptibility

93
Q

Protective or Susceptibility to cAD: probiotics, macrobiotic diet

A

Protective

94
Q

Protective or Susceptibility to cAD: Endotoxins

A

Protective

95
Q

Biodiversity hypothesis

A

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

96
Q

T or F: Probiotics can potentially ameliorate progression of cAD

A

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)

97
Q
A

EV ACVD Study (21 decks)

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