Basement Membrane Zone

Question 1

what is the basement membrane zone?

Answer 1

a complex structure that provides dermo-epidermal adhesion and regulates many important processes such as cell differentiation, motility, and the transmission of extracellular signals.

Question 2

what do the ultrastructures of the BMZ include?

Answer 2

Hemidesmosomes (BP 230, BP 180)
Lamina lucida (BP 180)
Lamina densa (laminin 332, collagen IV)
Sublamina densa (collagen VII)

Question 3

what are hemidesmosomes?

Answer 3

small structures on the inner surface of basal keratinocytes that are composed of many structural proteins. They are similar in form to desmosomes when visualized by electron microscopy.

Question 4

how are hemidesmosomes different from desmosomes?

Answer 4

While desmosomes link two cells together, hemidesmosomes attach one cell to the extracellular matrix

Question 5

what is Bullous Pemphigoid Antigen 1?

Answer 5

BP 230. it belongs to the plakin family of proteins, has cytoplasmic localization and is important for the organization of the cytoskeletal architecture

Question 6

what is bullous pemphigoid antigen 2?

Answer 6

Now referred to as type XVII collagen, BP 180 is a transmembrane protein connecting basal keratinocytes and cytoskeleton (via BP 230) to dermal collagen VII (via laminin 332).

Question 7

what is the second layer of the BMZ? where?

Answer 7

Immediately underlying hemidesmosomes is a thin structure known as the lamina lucida (LL). Newer techniques using high-pressure freeze substitution electron microscopy suggest that LL may be an artifact of tissue preparation and dehydration.

Question 8

what is the lamina densa composed of?

Answer 8

mostly type IV collagen and laminins

Question 9

what is type IV collagen?

Answer 9

this is one of the most abundant collagenous glycoproteins of the BMZ, comprising more than half of its mass. it is a heteropolymer which polymerizes into a triple helix and lattice formation

Question 10

the most abundant non-collagenous BMZ glycoproteins?

Answer 10

laminins

Question 11

he key BMZ laminin is?

Answer 11

laminin 332

Question 12

Laminin-332 binds to?

Answer 12

this binds to the transmembrane protein of the hemidesmosome integrin α6β4 using the G domain on its α3 chain, as well as to type VII collagen using its NC-1 domain, bridging the BMZ.

Question 13

what is type VII collagen made of?

Answer 13

large protein, composed of three identical alpha-chains that form anchoring fibrils

Question 14

what is the role of type VII collagen?

Answer 14

it is necessary to maintain epidermal-dermal cohesion, since it binds to both type I and type IV collagens, which further allows the type VII collagen molecule to join the lamina densa to the papillary dermis

Question 15

what is the process of a routine biopsy? what does it determine?

Answer 15

taken from the edge of blister and processed by regular histologic (hematoxylin & eosin, H&E) staining to determine blister level and inflammatory infiltrate.

Question 16

what does DIF do?

Answer 16

helps detect molecules such as immunoglobulins and complement (C3) within biopsy specimens.

Question 17

where are DIF samples taken from?

Answer 17

The skin samples are taken from perilesional skin.

Question 18

what does DIF detect? how?

Answer 18

Commercially-available fluorescein-conjugated antibodies against human immunoglobulins or complement are used to detect in-situ (in the patient skin) deposits of immunoreactants under the fluorescence microscope.

Question 19

what does IIF detect?

Answer 19

detects circulating antibody against BMZ in the patient’s serum

Question 20

what are the two steps of IIF?

Answer 20

In the first step, the patient serum is applied to a foreign substrate such as normal human skin (sometimes with an artificial split at the level of the lamina lucida created by salt), monkey esophagus, or rodent bladder. The circulating antibodies from the sera bind to the BMZ antigen in the substrate. In the second step, the antibody antigen complex is detected by fluorescein-conjugated antibody and visualized under the fluorescence microscope.

Question 21

what is ELISA used for? why is it helpful?

Answer 21

used as an initial screen for detection of patient’s circulating
autoantibodies. Based on the principle of antibody-antibody interaction, this test allows for easy visualization of results and can be completed in a short period of time.

Question 22

what type of IgG is used in DIF

Answer 22

tissue bound IgG

Question 23

what type of IgG is used in IIF?

Answer 23

circulating IgG

Question 24

what are the inherited blistering disorders of the BMZ called/group name?

Answer 24

epidermolysis bullosa. 4.
 Bullous pemphigoid
 Mucous membrane pemphigoid
 Epidermolysis bullosa acquisita
 Pemphigus vulgaris (discussed in the Epidermis section)

Question 25

what is the most common autoimmune bullous dermatosis?

Answer 25

bullous pemphigoid

Question 26

BP occurs in whom? how does it appear?

Answer 26

occurs primarily in the elderly. BP starts with pleomorphic clinical features, eg highly pruritic urticaria without blistering. then tense blisters with serous or rarely even hemorrhagic content appear in phases. blisters are extremely stable

Question 27

why are the BP blisters stable?

Answer 27

in contrast to the pemphigus group of diseases, the roof of the blister consists of the entire epidermis

Question 28

what are the autoantibodies directed against?

Answer 28

antibodies are directed against BP antigen 1 (BP 230) and BP antigen 2 (BP 180), causing subepidermal blisters

Question 29

what does DIF show? IIF? ELISA?

Answer 29

DIF shows linear deposits of IgG and C3 along the BMZ. IIF usually shows linear staining of on the epidermal side of salt-split skin. The BP 180 and BP 230 ELISA show positive results correlating with the disease activity.

Question 30

BP treatment? outcomes?

Answer 30

Less severe cases can be treated with high potency steroids. Oral steroids and other immunosuppressants are used for severe disease with caution due to potential side effects in the elderly population. better prognosis than PV.

Question 31

who does Mucous Membrane Pemphigoid affect? what do they get?

Answer 31

predominantly affects older people and is characterized by recurrent blistering of mucous membranes, but also the skin. Patients with this disorder develop scars, strictures, synechiae, and in 20% of cases, blindness.

Question 32

what are the antibodies formed in MMP?

Answer 32

majority of patients have antibodies against BP 180, but some patients have antibodies targeting BP 230, integrin β4, and laminin 332. in a subtype of MMP, anti-laminin 332 (epiligrin) pemphigoid, an association with malignancies has been reported in 30 % of cases; thus appropriate cancer screening examinations should be performed.

Question 33

what does DIF in MMP show? IIF?

Answer 33

DIF in MMP shows linear deposits of IgG and C3 along the BMZ. The IIF shows linear staining of epidermal, dermal and epidermal, or dermal (in the case of anti-laminin 332 MMP) side of salt-split skin substrate.

Question 34

what is EBA?

Answer 34

epidermolysis bullosa acquisita. rare autoimmune bullous dermatosis. Even slight trauma elicits blistering and erosions of the skin.

Question 35

EBA sites? results in?

Answer 35

mechanically-stressed areas such as hands, feet, elbows and knees. Healing of lesions leaves atrophy, milia, scars, and pigmentation disorders. Severe cases characterized by fibrosis of hands and feet. Nail dystrophy possible. often involvement of the oral mucosa in the form of hemorrhagic erosions.

Question 36

what is the EBA target antigen?

Answer 36

target antigen is type VII collagen.

Question 37

what does DIF show? IIF? ELISA?

Answer 37

DIF shows deposits of IgG and C3 along the BMZ. The IIF shows staining of dermal side of salt-split skin. Commercially-available ELISA testing is not available.

Question 38

what is epidermolysis bullosa (EB)?

Answer 38

Mutations in the genes encoding BMZ proteins result in the group of inherited skin fragility disorders known as EB.

Question 39

what does the absence of malfunction of these proteins lead to?

Answer 39

erosions and blisters after minimal mechanical trauma. broad spectrum of skin finding, depending on disease subtype. mutations in 10 different genes have been identified in different subtypes of EB.

Question 40

what are the targeted proteins in EB?

Answer 40

Targeted proteins include keratins 5 and 14, plectin, collagen types VII and XVII, α6β4 integrin, and laminin 332.

Question 41

what is epidermolysis bullosa simplex?

Answer 41

typically inherited in an autosomal dominant manner. The target proteins are keratins 5 and 14, which are present in basal keratinocytes

Question 42

what is junctional EB?

Answer 42

typically inherited in an autosomal recessive manner. The target proteins are laminin 332 and BP 180 at the BMZ.

Question 43

Dystrophic EB is?

Answer 43

inherited in both an autosomal dominant and recessive manner. The target protein is type VII collagen of the dermis.

Question 44

pemphigus vulgaris antigen?

Answer 44

desmoglein 1,3

Question 45

herlitz epidermolysis bullosa antigen?

Answer 45

laminin 332

Question 46

mucous membrane pemphigoid antigen?

Answer 46

laminin 332