Basement membrane zone - Croatia Flashcards
What is the function of integrins?
adhesion molecules that link the actin cytoskeleton to molecules of extracellular matrix
What are the main components of the anchoring fibrils in the sublamina densa?
collagen VII
Autoimmunity against BPAG2 (BP180, collagen XVII) results in what clinical disease? What species are affected?
Bullous pemphigoid – dogs, cats, pigs, horses; Mucous membrane (cicatricial) pemphigoid – dogs, cats; Linear IgA bullous disease – dogs
What breed of dogs is over-represented with mucous membrane pemphigoid?
GSDs
What body regions are frequently affected with Epidermolysis Bullosa Acquisita?
haired skin in areas of friction – axillae, groin, pinnae, footpads; oral cavity, lips, concave pinnae
In salt-split skin, what proteins will be on the “floor”?
laminin-332, collagen VII
In linear IgA dermatosis, anti-BMZ IgA and IgG is detected on which side of salt-split skin (ceiling or floor)?
Ceiling – epidermal side (collagen XVII part of hemidesmosome)
Sites of involvement for mixed autoimmune subepidermal blistering disease?
haired skin involvement with oral cavity lesions
To what do perlecans bind?
themselves, collagen IV, laminin (alpha-chains) – located inside lamina densa
Rowing of individual neutrophils and/or histiocytes along the basement membrane is a common histological feature of what disease?
epidermolysis bullosa acquisita
What would be a differential diagnosis for ulcerations at the lips/perilabial area?
mucoucutaneous lupus, mucous membrane pemphigoid
Recessive dystrophic epidermolysis bullosa has been reported in what species?
humans, white alpine and Assaf sheep, Rotes Hohenvieh and Voderwald cattle, dogs, cats
Mutations in LAMA3 (laminin alpha-3 chain) results in what clinical disease? In what species?
Junctional Epidermolysis Bullosa; GSP, American saddlebred horses, Belgian blue cattle
What is the function of keratins in keratinocytes?
forms cytoskeleton of epithelial cells
Histopathological features of bullous pemphigoid
dermo-epidermal separation (vesicle formation), inflammation in vesicles varible – neutrophils +/- eosinophils; degranulated mast cells in upper dermis
Is plectin part of the outer or inner plaque of the hemidesmosome?
inner plaque (intracytoplasmic)
Autoimmunity against laminin-5 has been associated with what clinical disease? In what species
Mucous membrane (cicatricial) pemphigoid: humans, one dog; Acquired junctional epidermolysis bullosa: reported in 5 dogs; Mixed subepidermal autoimmune blistering disease (dogs)
Epidermolysis Bullosa Simplex, basal, has been associated with mutations in what genes? In what species?
Keratin-5 (KRT5) and plectin (PLEC); KRT5 in Friesian-Jersey cattle, PLEC in a quarterhorse, Eurasier dogs
What is the most common autoimmune subepidermal blistering disease in humans? How common is it in dogs?
bullous pemphigoid, rare in dogs – less than 10% of AISBDs
To what does collagen VII bind?
laminin-332 (laminin-5), collagen IV, collagen I
To what in the hemidesmosome does collagen IV bind?
itself (collagen IV), laminin network via nidogens + fibulins, perlecan
What is the function of nidogens?
Link laminins and collagen
Junctional Epidermolysis Bullosa has been reported in what species?
lethal variant: humans, dogs, horses, cattle; localized: GSP, American saddlebreds, Belgian blue cattle, draft horses (Belgian, Breton, Comtois and Italian), German black-headed sheep; Intermediate: Charolais cattle, Churra sheep
Acquired junctional epidermolysis bullosa can result from autoimmunity against what structure?
Laminin 332 (laminin-5)
Anti-BMZ IgG autoantibodies can be detected in the (ceiling/floor) in Epidermolysis Bullosa Acquisita
Floor (target is in lamina densa, i.e. dermis – collagen VII)
Bullous pemphigoid results from autoimmunity against what structures?
BP230 (BPAG1-e) = plakin, BP180 (BPAG2, collagen XVII)
To what in the hemidesmosome does BPAG1-e (BP230) bind?
keratin intermediate filaments, collagen XVII (cytoplasmic head), integrin beta-4 (carboxyl terminus)
Recessive dystrophic epidermolysis bullosa is associated with mutations in genes that encode for what structures?
collagen VII
When keratinocytes start migration from stratum basale to stratum spinosum, what part of hemidesmosome is cleaved?
collagen XVII– results in a new protein that lacks a cytoplasmic and transmembrane domain (LAD-1)
What collagens are found in the epidermal basement membrane?
collagen XVII, IV and VII
Mutations in the gene that encodes for keratin-5 (KRT5) results in what clinical disease? In what species is it reported?
Basal Epidermolysis Bullosa (EB) Simplex variants; cattle
Epidermolysis Bullosa Simplex has been associated with mutations in genes that encode for what molecules?
plectin, keratin-5
What in the basement membrane is stained by Periodic Acid-Schiff stain? Why?
perlecans, stains polysaccharides (the proteoglycans)
What is LAD-1?
cleaved product of collagen XVII that lacks a cytoplasmic and transmembrane domain
Bullous pemphigoid has been reported in what species?
dogs, cat (1 case), Yucatan mini-pigs, horses (2-3 cases)
Mutations in COL7A1 (Collagen VII) results in what clinical disease? In what species?
Dystrophic Epidermolysis Bullosa; sheep, cattle, dogs, cats, ostrich
T/F: Autoantibodies, predominantly IgG and complement, can be detected along the basement membrane zone in mucous membrane pemphigoid.
TRUE
T/F: There are varying phenotypes associated with Dystrophic Epidermolysis Bullosa. Why or why not?
True - can have a complete absence of collagen VII or alteration of function (due to truncation of molecules or change in conformation)
Mutations in the gene that encodes for laminin-5 (LAMA3, LAMB3, LAMC2) have been associated with what diseases? In what species?
lethal junctional epidermolysis bullosa (dogs, horses, cattle); localized junctional epidermolysis bullosa (LAMA3: German shorthaired pointers, American saddlebreds, Belgian blue cattle), LAMC2: Belgian, Breton, Comtois and Italian draft horses, German black-headed sheep
What is the function of plakins?
cytolinkage, can bind multiple types of proteins
What is the most important laminin in the epidermal basement membrane?
Laminin-5 (LM332 = 3 alpha chains, 3 beta chains, 2 gamma chains)
T/F: Footpad involvement is commonly seen with both mucous membrane pemphigoid and epidermolysis bullosa acquisita
False - only EBA
What therapies have been used in treatment of mucous membrane pemphigoid?
glucocorticoids, tetracycline + niacinamide, azathioprine, chlorambucil, mycophenolate, cyclosporine
Mutations in ITGB4 (integrin beta-4) result in what clinical disease? In what species?
Junctional Epidermolysis Bullosa; Charolais cattle, Churra sheep
Linear IgA Dermatosis results from autoantibodies to what structure?
processed extracellular domain of collagen XVII
What are the two keratins present in the stratum basale keratinocytes?
keratin-5 and keratin-14