ICADA molecular pathogenesis of cAD Flashcards
T or F: the inheritance of cAD is Mendelian modality
F. Polygenic, epigenetic changes
Which dogs have a SNP mutation in the filaggrin gene (FLG), associated with their cAD?
UK Labrador retrievers
Primary Afferent nerve receptors in the skin
*Unmyelinated C fibers
*Thinly myelinated Aδ fibers
Where are the cell bodies of the nerves the innervate the skin?
Dorsal root ganglion
Where does the dorsal root ganglia synapse in the spinal cord to further induce activation of the itch signaling pathway
Dorsal horn of the spinal cord
What length of time defines “chronic” pruritus
6 weeks
2 divisions of peripheral itch transmission
*Histamine-dependent
*Non-histamine dependent
Is human AD primarily histamine-dependent or nonhistamine dependent?
NONhistamine dependent
No studies in dogs, so extrapolating from humans
RNA for which pruritogenic proteins are upregulated in cAD?
*Cathepsin S
*CTSC
*Chymase
*Mastin
*Substance P
*Neuromedin B
*Nerve growth factor
*NGF receptor TrkA
*Periostin
*Leukotriene synthesis enzymes (ALOX5, ALOX5AP, LTA4H)
T or F: mRNA for IL-31 is upregulated in cAD skin
F. Santoro believes rRNA may be temporary, unstable, or issues with our primers.
What receptor complex does IL-31 bind to, initiating pruritus
*IL-31RA
*Oncostatin M receptor (OSMR)
Downstream: phosphorylates JAK, STAT, PI3K/AKT
T or F: intraepidermal nerve fiber density is increased in cAD skin
TRUE
Is there increased or decreased FLG2 expression in cAD skin?
Decreased
Function of FLG2
Activates SASPase (protease that processes profilaggrin to filaggrin)
Is there an increase or decreased in FLG expression in cAD skin?
Increased!
Unusual. Different from humans
