Background

The basement membrane zone (BMZ) of the skin is a dynamic area of research. It is the anchoring complex joining the epidermis and derms of the skin. To best understand the importance of the different components of the BMZ, the corresponding disease states are included. The anchoring complex is composed of the hemidesmosomes, anchoring filaments, and anchoring fibrils. See the keratinocyte for more information regarding the hemidesmosome.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

The basic structure of the BMZ is an interaction between the following structures:

Component	Description
Basal keratinocytes-epidermal side	BP180 BP230 Plectin
Basal keratinocytes-dermal side	BP180/NC16A alpha6beta4 integrin
Lamina lucida	p200 Laminin 6 p105
Lamina densa	BP180 Laminin 5
Sublamina densa	Collagen type VII Dermal collagen including collagen type IV
Components spanning the BMZ (transmembrane proteins)	BP180 Plectin

 

Proteins Localized to the Hemidesmosome

Plectin BP230 BP180 alpha6beta4 integrin

 

Basement Membrane Components	Type IV collagen-Lamina densa Laminin-Lamina lucida Heparan sulfate-Clusters on either side of LD Bullous pemphigoid antigen-Basal cell plasma membrane EBA antigen-Lamina densa-sublamina densa
	Bullous pemphigoid antigens Laminin 5 Uncein Ladinin (LAD-1) EBA antigen
Bullous Pemphigoid Antigen
BPAg1 (230kd)	Intracellular associated with hemidesmosomes Homology with desmoplakin 70% of BP pts have circulating Ab to this
BPAg2 (180kd)	Intra and extracellular with collagen-like domains Also called collagen XVII Extramembranous protion is antigenic epitope site for BP and HG
Laminin 5	Lamina lucida Identical to epiligrin Also called BM600, nicein, and kalinin Antibodies found in: Antiepiligrin cicatricial pemphigoid Some forms of junctional EB
Uncein	Anchoring filament related to laminin 5 Antibodies found in: Overlap syndrome with features of CP and EBA
Ladinin (LAD-1)	Component of anchoring filaments Lamina lucida Antibodies found in: Linear IgA disease Chronic bullous disease of childhood
EBA Antigen	Within and subjacent to lamina densa Constituent molecule of anchoring fibrils attaching BM to underlying dermis Noncollagenous domain of type VII collagen Mainly synthesized by keratinocytes

The pathologist has a number of tools that can further identify the location of some of these structures.

INDIRECT IMMUNOFLUORESCENCE MICROSCOPY WITH 1 MOL/L SALT-SPLIT HUMAN SKIN

Epidermal side of split	Bullous pemphigoid Pemphigoid gestationis Lichen planus pemphigoides
Dermal side of split	Epidermolysis bullosa acquisita Anti-p200 pemphigoid Anti-p105 pemphigoid
Both epidermal and dermal	Linear IgA disease Cicatricial pemphigoid Bullous SLE

When these structures and proteins are studied in detail, it is easy to understand why this Salt Split Skin technique has localization of the various components to the epidermal, dermal, or both sides of the BMZ.

Molecular Interactions	Autoimmune Disorder	Genetic Disease	Affected Gene	Variant of Epidermolysis bullosa (EB)
Keratin intermediate filaments, micortubules, actin, BP180, beta4 integrin	Paraneoplastic pemphigus	EB with muscular dystrophy EB Ogna ?	PLEC1	Hemidesmosomal
Keratin intermediate filaments, BP180	Bullous pemphigoid Pemphigoid gestationis Lichen planus pemphigoides Linear IgA disease Cicatricial pemphigoid	-	-	-
alpha6beta4 integrin, BP230, plectin, laminin	Bullous pemphigoid Pemphigoid gestationis Lichen planus pemphigoides Linear IgA disease Cicatricial pemphigoid	Generalized atrophic benign EB (GABEB)	COL17A1	Hemidesmosomal
beta4 integrin, BP180, NC16A, laminin 5 alpha6 integrin, BP180, plectin, laminin5	Cicatricial pemphigoid	EB with pyloric atresia	ITGA6 ITGB4	Hemidesmosomal
Laminin 6, alpha6beta4 integrin, BP180, type VII collagen	Cicatricial pemphigoid Bullous SLE	Herlitz Junctional EB, GABEB, Localized junctional EB	LAMA3 LAMB3 LAMC2	Junctional
Laminin 5	Cicatricial pemphigoid Bullous SLE	-	-	-
Laminin 5, type IV collagen	EBA Bullous SLE	Dystrophic EB	COL7A1	Dystrophic

Adv Dermatol 2000; 16;113-157.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Alpha6beta4 integrin-Beta 4 integrin subunit is noncovalently bound to alpha6 subunit. Trasmembrane alpha6beta4 integrin interacts with the anchoring complex (BP180, plectin, laminin 5). Also plays a role in hemidesmosome assembly. After ligation with laminin 5, it is important for cell proliferation, differentiation, and migration.

Cell

Collagen VII-Collagen variant present in the skin basement membrane within the anchoring fibrils.

Keratinocyte

Laminin 5-Widely distributed in various epithelia. Localizes to the anchoring filaments of the lamina lucida and also within the lamina densa of the basement membrane zone.

Plectin-Cytoskeletal linker protein in skin and muscle-member of the plakin family. Located in the hemidesmosomal and hemidesmosomal plaques interacting with the cytoskeletal proteins. Separation occurs at the level of the hemidesmosomal plaque

Salt split skin assay-Normal skin incubated with 1M NaCl which separates the epidermis from dermis. The epidermal half contains the upper lamina lucida, hemidesmosomes, and BP antigen. The dermal half contains laminin 5, lamina densa, and anchoring fibrils.

Skin

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Special Stains
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Last Updated April 10, 2006

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