Table 1.

Major proteases in pemphigoid diseases.

Protease	Class	Location in PD	Functions in PD	References
NE	serine protease	BP—blister fluids	BP, EBA Hemidesmosomal protein degradation (COL17 and laminin-332)	(95, 122–127)
MMP-2 (gelatinase A, 72 kDa type IV collagenase)	Metalloprotease	BP—blister fluids, lesional skin EBA—sera MMPh—tear, sera	EBA Complexed with Hsp-90	(124, 156, 165, 166)
MMP-3 (stromelysin-1)	Metalloprotease	BP—serum, lesional skin	Negative in BP mouse model	(163, 167, 168)
MMP-9 (gelatinase B, 92 kDa type IV collagenase)	Metalloprotease	BP—lesional and perilesional skin, blister fluid MMPh—tear	BP, EBA NE activation through α1-AT degradation CD46 shedding	(96, 124, 125, 148, 155–160, 163, 164)
MMP-12 (macrophage elastase)	Metalloprotease	EBA—sera BP—lesional skin	EBA Complexed with Hsp-90	(166, 169)
MMP-13 (collagenase-3)	Metalloprotease	BP—lesional skin	Unknown	(156)
Plasmin, plasminogen, tPA, and uPA	Serine protease	BP—blister fluid, lesional skin	BP MMP-9 activation COL17 shedding	(163, 201–207)
Chymase/mMCP-4	Serine protease	BP—non lesional skin	BP MMP-9 activation COL17 degradation	(244, 304)
Granzyme B	Serine protease	BP, EBA, DH—lesional skin	DEJ protein degradation (COL7, α6β4 integrins, COL17) IL-1α activation C5a production	(298, 299)
ADAM-8	Metalloprotease	BP—epidermis of lesional skin	Unknown	(159, 258, 259)
ADAM-9	Metalloprotease	BP—epidermis of lesional skin	COL17 shedding	(159, 258, 259)
ADAM-10	Metalloprotease	BP—epidermis of lesional skin	COL17 shedding CD46 shedding Semaphorin 4D shedding	(159, 164, 258, 259)
ADAM-15	Metalloprotease	BP—epidermis of lesional skin	Unknown	(159, 258, 259)
ADAM-17	Metalloprotease	BP—epidermis of lesional skin	(Indirect) COL17 shedding	(159, 258, 259)
Tryptase	Serine protease	BP—blister fluid, sera	Unknown	(302–304)
Cathepsin-G	Serine protease	BP	Negative in BP mouse model	(126, 163, 301)