Basement membrane zone - Croatia Flashcards
(116 cards)
1
Q
What is the function of integrins?
A
adhesion molecules that link the actin cytoskeleton to molecules of extracellular matrix
2
Q
What are the main components of the anchoring fibrils in the sublamina densa?
A
collagen VII
3
Q
Autoimmunity against BPAG2 (BP180, collagen XVII) results in what clinical disease? What species are affected?
A
Bullous pemphigoid – dogs, cats, pigs, horses; Mucous membrane (cicatricial) pemphigoid – dogs, cats; Linear IgA bullous disease – dogs
4
Q
What breed of dogs is over-represented with mucous membrane pemphigoid?
A
GSDs
5
Q
What body regions are frequently affected with Epidermolysis Bullosa Acquisita?
A
haired skin in areas of friction – axillae, groin, pinnae, footpads; oral cavity, lips, concave pinnae
6
Q
In salt-split skin, what proteins will be on the “floor”?
A
laminin-332, collagen VII
7
Q
In linear IgA dermatosis, anti-BMZ IgA and IgG is detected on which side of salt-split skin (ceiling or floor)?
A
Ceiling – epidermal side (collagen XVII part of hemidesmosome)
8
Q
Sites of involvement for mixed autoimmune subepidermal blistering disease?
A
haired skin involvement with oral cavity lesions
9
Q
To what do perlecans bind?
A
themselves, collagen IV, laminin (alpha-chains) – located inside lamina densa
10
Q
Rowing of individual neutrophils and/or histiocytes along the basement membrane is a common histological feature of what disease?
A
epidermolysis bullosa acquisita
11
Q
What would be a differential diagnosis for ulcerations at the lips/perilabial area?
A
mucoucutaneous lupus, mucous membrane pemphigoid
12
Q
Recessive dystrophic epidermolysis bullosa has been reported in what species?
A
humans, white alpine and Assaf sheep, Rotes Hohenvieh and Voderwald cattle, dogs, cats
13
Q
Mutations in LAMA3 (laminin alpha-3 chain) results in what clinical disease? In what species?
A
Junctional Epidermolysis Bullosa; GSP, American saddlebred horses, Belgian blue cattle
14
Q
What is the function of keratins in keratinocytes?
A
forms cytoskeleton of epithelial cells
15
Q
Histopathological features of bullous pemphigoid
A
dermo-epidermal separation (vesicle formation), inflammation in vesicles varible – neutrophils +/- eosinophils; degranulated mast cells in upper dermis
16
Q
Is plectin part of the outer or inner plaque of the hemidesmosome?
A
inner plaque (intracytoplasmic)
17
Q
Autoimmunity against laminin-5 has been associated with what clinical disease? In what species
A
Mucous membrane (cicatricial) pemphigoid: humans, one dog; Acquired junctional epidermolysis bullosa: reported in 5 dogs; Mixed subepidermal autoimmune blistering disease (dogs)
18
Q
Epidermolysis Bullosa Simplex, basal, has been associated with mutations in what genes? In what species?
A
Keratin-5 (KRT5) and plectin (PLEC); KRT5 in Friesian-Jersey cattle, PLEC in a quarterhorse, Eurasier dogs
19
Q
What is the most common autoimmune subepidermal blistering disease in humans? How common is it in dogs?
A
bullous pemphigoid, rare in dogs – less than 10% of AISBDs
20
Q
To what does collagen VII bind?
A
laminin-332 (laminin-5), collagen IV, collagen I
21
Q
To what in the hemidesmosome does collagen IV bind?
A
itself (collagen IV), laminin network via nidogens + fibulins, perlecan
22
Q
What is the function of nidogens?
A
Link laminins and collagen
23
Q
Junctional Epidermolysis Bullosa has been reported in what species?
A
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
24
Q
Acquired junctional epidermolysis bullosa can result from autoimmunity against what structure?
A
Laminin 332 (laminin-5)
25
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)
26
Bullous pemphigoid results from autoimmunity against what structures?
BP230 (BPAG1-e) = plakin, BP180 (BPAG2, collagen XVII)
27
To what in the hemidesmosome does BPAG1-e (BP230) bind?
keratin intermediate filaments, collagen XVII (cytoplasmic head), integrin beta-4 (carboxyl terminus)
28
Recessive dystrophic epidermolysis bullosa is associated with mutations in genes that encode for what structures?
collagen VII
29
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)
30
What collagens are found in the epidermal basement membrane?
collagen XVII, IV and VII
31
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
32
Epidermolysis Bullosa Simplex has been associated with mutations in genes that encode for what molecules?
plectin, keratin-5
33
What in the basement membrane is stained by Periodic Acid-Schiff stain? Why?
perlecans, stains polysaccharides (the proteoglycans)
34
What is LAD-1?
cleaved product of collagen XVII that lacks a cytoplasmic and transmembrane domain
35
Bullous pemphigoid has been reported in what species?
dogs, cat (1 case), Yucatan mini-pigs, horses (2-3 cases)
36
Mutations in COL7A1 (Collagen VII) results in what clinical disease? In what species?
Dystrophic Epidermolysis Bullosa; sheep, cattle, dogs, cats, ostrich
37
T/F: Autoantibodies, predominantly IgG and complement, can be detected along the basement membrane zone in mucous membrane pemphigoid.
TRUE
38
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)
39
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
40
What is the function of plakins?
cytolinkage, can bind multiple types of proteins
41
What is the most important laminin in the epidermal basement membrane?
Laminin-5 (LM332 = 3 alpha chains, 3 beta chains, 2 gamma chains)
42
T/F: Footpad involvement is commonly seen with both mucous membrane pemphigoid and epidermolysis bullosa acquisita
False - only EBA
43
What therapies have been used in treatment of mucous membrane pemphigoid?
glucocorticoids, tetracycline + niacinamide, azathioprine, chlorambucil, mycophenolate, cyclosporine
44
Mutations in ITGB4 (integrin beta-4) result in what clinical disease? In what species?
Junctional Epidermolysis Bullosa; Charolais cattle, Churra sheep
45
Linear IgA Dermatosis results from autoantibodies to what structure?
processed extracellular domain of collagen XVII
46
What are the two keratins present in the stratum basale keratinocytes?
keratin-5 and keratin-14
47
What is the most common haired skin body region exhibiting skin lesions with mucous membrane pemphigoid in dogs?
concave pinna
48
In the single report of bullous systemic lupus erythematosus, which came first, cutaneous subepidermal vesicles or systemic signs?
systemic signs
49
T/F: Mucosal involvement in bullous pemphigoid is uncommon.
True - primarily a skin-dominant autoimmune subepidermal blistering disease
50
In Epidermolysis bullosa acquisita, staining of salt-split skin with collagen IV results in stain on the top or bottom of the blister?
Top -- (collagen IV is within the basal keratinocyte), separation is deep (target is collagen VII)
51
Mutations in the gene that encodes for plectin (PLEC) has been associated with what clinical disease(s)? In what specie(s)?
Epidermolysis Bullosa Simplex and Laminitis (horses); Epidermolysis Bullosa Simplex (EBS Plectin) in Eurasier dogs
52
What are clinical signs associated with Epidermolysis Bullosa Acquisita?
vesicles and bullae, erosions and ulcers, erythematous macules and patches
53
To what family does BPAG1-e (BP230) belong?
plakin
54
Junctional Epidermolysis bullosa acquisita results from autoantibodies against what structure(s)?
laminin-332 (laminin-5) -- the alpha-3 and beta-3 chains
55
What is the common signalment for epidermolysis bullosa acquisita?
young animals (median age 1.2 years), Great Danes over-represented
56
T/F: Systemic signs are commonly reported with mucous membrane pemphigoid.
False -- signs reflect location of lesions (i.e. oral cavity pain, reduced appetite, halitosis, etc.)
57
What are clinical lesions associated with mucous membrane pemphigoid?
erosions/ulcers (#1), intact vesicles/bullae, scarring (infrequent)
58
T/F: Both circulating and tissue-bound autoantibodies can be detected in Epidermolysis bullosa acquisita.
TRUE
59
Genetic mutations in genes ITGB4 (encodes for integrin beta-4) have been associated with what disease(s) in what specie(s)?
Junctional Epidermolysis Bullosa, generalized intermediate (JEB-gen intermed) in Charolais calves and Churra sheep
60
To what in the hemidesmosome does integrin alpha-6/beta-4 bind?
outer plaque, alpha-6 chain: NC16A extracellular domain of collagen XVII (BPAG2, BP180); beta-4 chain: cytoplasmic carboxyl terminus binds to head of collagen XVII, plectin, BPAG1-e; aminal terminus of both chains binds laminin-5 and laminin-10 (inner plaque)
61
What are the main components of the anchoring filaments?
collagen XVII (BPAG2, BP180)
62
Autoantibodies in canine mucous membrane pemphigoid have been detected against what structures?
collagen XVII (BPAG2, BP180), BP230 (BPAG1e), laminin-332 (laminin-5)
63
Synonyms for Collagen XVII
BPAG2, BP180
64
Bullous systemic lupus erythematosus clinically resembles what other disease?
epidermolysis bullosa acquisita
65
What are the epidermal plakins found in hemidesmosomes?
BPAG-1, plectin
66
T/F: Mucous membrane pemphigoid is confined to the mucosae and mucocutaneous junctions.
False - the skin can be affected with minor lesions (10-30% of cases have skin lesions)
67
What is the mode of transmission of inherited epidermolysis bullosa?
autosomal recessive
68
What are anchoring filaments?
connect hemidesmosomes to anchoring fibrils throughout the lamina lucida
69
What is the difference in autoantigen between canine Junctional Epidermolysis Bullosa Acquisita and traditional EBA?
JEBA - laminin-332, EBA- collagen VII
70
What are the sites of attachment of keratin filaments?
nucleus (nuclear laminin B), desmosome, hemidesmosome, other keratin intermediate filaments
71
Canine mixed autoimmune subepidermal blistering disease clinically resembles what other disease?
bullous pemphigoid
72
Mutations in LAMC2 (laminin gamma-2 chain) results in what clinical disease? In what species?
Junctional Epidermolysis Bullosa; draft breed horses of European origin (Breton, Comtois, Belgian), German black-head mutton sheep, Danish Herefords
73
In what species has epidermolysis bullosa acquisita been reported?
humans, dogs
74
What is the most common autoimmune subepidermal blistering disease in dogs?
mucous membrane pemphigoid
75
To what in the basement membrane zone does laminin-332 bind?
alpha-3 binds integrin alpha-6/beta-4, beta-3 binds to NC1 domain of collagen VII, BPAG2 (collagen XVII)
76
Autoantibodies in mixed Autoimmune subepidermal blistering disease have been detected against what structures?
laminin-332 AND collagen VII
77
Mucous membrane pemphigoid can result from autoimmunity against what structures?
BP230 (BPAG1-e)= plakin, BP180 (BPAG2, collagen XVII) - NC domain and carboxyl terminus
78
Histopathological features of epidermolysis bullosa acquisita
dermo-epidermal separation (vesicle formation), inflammation in vesicles varible -- neutrophils +/- eosinophils; early lesions - subepidermal vacuoles with rowing of neutrophils +/- histiocytes along BMZ
79
In salt-split skin, what diseases will result in stain uptake (i.e. autoantibodies) in either the roof or the floor?
mucous membrane pemphigoid, Junctional EBA
80
What are the main components of the inner plaque of the hemidesmosome?
plectin + BPAG1-e
81
What are the main components of a collagen domain?
triads of glycine-amino acid 1- amino acid 2
82
Epidermolysis Bullosa Acquisita can result from autoimmunity against what structure?
collagen VII (NC domain)
83
Junctional Epidermolysis Bullosa has been associated with mutations in what genes?
ITGB4 (integrin beta-4), laminin 332: LAMA3 (alpha-3 chain), LAMC2 (gamma-2 chain)
84
Besides the skin, where else is collagen IV found?
glomerular basement membrane
85
In salt-split skin, what diseases will result in stain uptake (i.e. autoantibodies) in the roof (i.e. epidermis)?
bullous pemphigoid, MMP (where target antigen is XVII), linear IgA dermatosis
86
Where are focal contacts present?
keratinocyte membrane, lamina densa
87
What clinical diseases in animals have been associated with mutations in EPPK1 or autoantibodies against epiplakin-1?
none
88
What distinguishes junctional epidermolysis bullosa from epidermolysis bullosa simplex, basal?
clefting occurs above perlecan or between alpha-6 integrin and collagen IV (above lamina densa) in junctional EB
89
T/F: Systemic signs are commonly reported with epidermolysis bullosa acquisita.
True-- pruritus, pain, lethargy, fever, lymphadenopathy, anorexia
90
Mutations in the gene that encodes for collagen VII (COL7A1) results in what clinical disease? In what species?
Recessive Dystrophic Epidermolysis Bullosa (RDEB, various subtypes) -- white alpine and Assaf sheep, Rotes Hohenvieh and Voderwald cattle, dogs, cats
91
Autoimmunity against BPAG1-e (BP230) results in what clinical disease?
Bullous pemphigoid (dogs); Mucous membrane pemphigoid (dogs); Paraneoplastic Pemphigus (dogs)
92
In what species has acquired junctional epidermolysis bullosa been reported?
dogs
93
What are the main components of the lamina densa of the hemidesmosome?
collagen IV + laminin + nidogens + perlecan + proteoglycans + fibulins
94
Autoimmunity against collagen VII results in what clinical disease(s)? In what species?
Epidermolysis Bullosa Acquisita** (dogs), Type I bullous Systemic Lupus Erythematosus (reported in one dog)
95
What are the main components of the outer plaque of the hemidesmosome
integrin alpha-6/beta-4 + cytoplasmic domain of collagen XVII (=BPAG2, BP180)
96
Mixed subepidermal Autoimmune blistering disease can result from autoimmunity against what structure?
Laminin 332 (laminin-5)
97
Histopathological features of canine mucous membrane pemphigoid
subepidermal or submucosal vesicles -- intact usually devoid of inflammation; dermal inflammation usually mild with both neutrophils and eosinophils seen below vesicles or the intact epithelium
98
What is the second most common autoimmune subepidermal blistering disease in dogs?
epidermolysis bullosa acquisita
99
Where is the best place to biopsy when an autoimmune subepidermal blistering disease is suspected?
ulcer margin with adjacent intact skin
100
Where does plectin bind in the hemidesmosome?
keratin intermediate filaments, integrin beta-4 (cytoplasmic tail), collagen XVII (cytoplasmic head)
101
What body sites are commonly affected with mucous membrane pemphigoid?
oral cavity, nose/nasal planum, lips, anogenital, periocular, concave pinna
102
To what in the hemidesmosome does collagen XVII (BPAG2, BP180) bind?
cytoplasmic side: globular head of collagen XVII interacts with integrin beta-4, plectin, and BPAG1-e; transmembrane section: NC16A (noncollagenous segment) binds to aminal terminus of integrin alpha-6, carboxyterminus binds to laminin-5 (in lamina densa)
103
Junctional Epidermolysis bullosa acquisita in dogs affects what areas of the body?
haired skin, footpads, oral mucosa
104
Clinical signs associated with bullous pemphigoid
deep erosions/ulcers, erythematous macules/patches/plaques, vesicles/bullae
105
T/F: Both circulating and tissue-bound autoantibodies can be detected in bullous pemphigoid.
TRUE
106
What are clinical signs associated with Dystrophic Epidermolysis Bullosa?
vesicles (flaccid, clear or hemmorhagic) at mucocutaneous junctions and areas of friction (lips, muzzle, ears, groin, coronary bands, soles, footpads)
107
What are perlecans also known as?
heparan sulfate proteoglycan
108
In what species has mixed subepidermal autoimmune blistering disease been reported?
dogs
109
T/F: Mucous membrane pemphigoid has been reported in the cat.
True - two cats, autoantibodies targeting collagen XVII and laminin-332
110
where in the hemidesmosome-anchoring fibril adhesion complex is collagen IV found?
lamina densa
111
What is the common signalment for bullous pempigoid in dogs?
middle aged (median age 5 years), daschunds and GSDs reported in 2/9 cases each
112
T/F: Circulating autoantibodies of anti-BMZ proteins are a common feature of mucous membrane pemphigoid.
False -- low sensitivity
113
Epidermolysis bullosa simplex, suprabasal, has been associated with mutations in what gene? In what species?
PKP1 (plakophilin-1), Chesapeake Bay retrievers (caused ectodermal dysplasia-skin fragility syndrome)
114
In salt-split skin, what diseases will result in stain uptake (i.e. autoantibodies) in the floor (i.e. dermis)?
Epidermolysis bullosa acquisita, MMP (where target antigen is laminin-332), Junctional EBA, mixed AISBD, bullous SLE
115
Junctional Epidermolysis Bullosa has been associated with mutations in genes that encode for what structures?
integrins (beta-4), laminin-5 (laminin 332) - mutations in alpha-3 chain, beta-3 or gamma-2 chain
116
What are focal contacts?
inter-hemidesmosomal adhesion structures that are mostly functional during wound healing & epidermal migrations
