Desmosomes and disease: Pemphigus and bullous impetigo

Current Opinion in Cell Biology

Volumn 16, Issue 5, 2004, Pages 536-543

  Payne, Aimee S ^a   Hanakawa, Yasushi ^b   Amagai, Masayuki ^c   Stanley, John R ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b EHIME UNIVERSITY   (Japan)

^c KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

desmoglein; Dsg; ET; exfoliative toxin; fogo selvagem; FS; IgG; immunoglobulin G; mAb; methylprednisolone; monoclonal antibody; MP; pemphigus foliaceus; pemphigus vulgaris; PF; PV; SSSS; staphylococcal scalded skin syndrome

Indexed keywords

ANTIBODY; CHOLINERGIC RECEPTOR STIMULATING AGENT; CHOLINESTERASE INHIBITOR; CORTICOSTEROID; DESMOGLEIN; DESMOGLEIN 1; DESMOGLEIN ANTIBODY; EPITOPE; METHYLPREDNISOLONE; UNCLASSIFIED DRUG;

ACANTHOLYSIS; AMINO TERMINAL SEQUENCE; ANTIBODY PRODUCTION; AUTOIMMUNE DISEASE; CELL ADHESION; DESMOSOME; EXTRACELLULAR SPACE; HUMAN; IMPETIGO BULLOSA; IN VIVO STUDY; PATHOLOGY; PEMPHIGUS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; TOXIC EPIDERMAL NECROLYSIS;

ACANTHOLYSIS; ANTIBODIES; CADHERINS; CELL ADHESION; DESMOSOMES; EPITOPES; HUMANS; IMPETIGO; MODELS, BIOLOGICAL; PEMPHIGUS; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY;

PEMPHIGUS;

EID: 4444380149     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2004.07.006     Document Type: Review

References (63)

1. S. Getsios, A.C. Huen, and K.J. Green Working out the strength and flexibility of desmosomes Nat Rev Mol Cell Biol 5 2004 271 281
2. B.D. Angst, C. Marcozzi, and A.I. Magee The cadherin superfamily: diversity in form and function J Cell Sci 14 2001 629 641
3. M. Peifer, S. Berg, and A.B. Reynolds A repeating amino acid motif shared by proteins with diverse cellular roles Cell 76 1994 789 791
4. C. Ruhrberg, and F.M. Watt The plakin family: versatile organizers of cytoskeletal architecture Curr Opin Genet Dev 7 1997 392 397
5. J.R. Stanley Pemphigus I.M. Freedberg A.Z. Eisen K. Wolff K.F. Austen L.A. Goldsmith S.I. Katz Fitzpatrick's Dermatology in General Medicine vol 1 2003 McGraw-Hill 558 566
6. R.W. Eyre, and J.R. Stanley Human autoantibodies against a desmosomal protein complex with a calcium-sensitive epitope are characteristic of pemphigus foliaceus patients J Exp Med 165 1987 1719 1724
7. M. Amagai, V. Klaus-Kovtun, and J.R. Stanley Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion Cell 67 1991 869 877
8. N.J. Korman, R.W. Eyre, V. Klaus-Kovtun, and J.R. Stanley Demonstration of an adhering-junction molecule (plakoglobin) in the autoantigens of pemphigus foliaceus and pemphigus vulgaris N Engl J Med 321 1989 631 635
9. K. Ishii, M. Amagai, R.P. Hall, T. Hashimoto, A. Takayanagi, S. Gamou, N. Shimizu, and T. Nishikawa Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins J Immunol 159 1997 2010 2017
10. X. Ding, V. Aoki, J.M.J. Mascaro, A. Lopez-Swiderski, L.A. Diaz, and J.A. Fairley Mucosal and mucocutaneous (generalized) pemphigus vulgaris show distinct autoantibody profiles J Invest Dermatol 109 1997 592 596
11. M. Amagai, K. Tsunoda, D. Zillikens, T. Nagai, and T. Nishikawa The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile J Am Acad Dermatol 40 1999 167 170
12. S. Miyagawa, M. Amagai, T. Iida, Y. Yamamoto, T. Nishikawa, and T. Shirai Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: correlation with disease progression Br J Dermatol 141 1999 1084 1087
13. A. Komai, M. Amagai, K. Ishii, T. Nishikawa, T. Chorzelski, J. Matsuo, and T. Hashimoto The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay Br J Dermatol 144 2001 1177 1182
14. K.E. Harman, M.J. Gratian, P.J. Shirlaw, B.S. Bhogal, S.J. Challacombe, and M.M. Black The transition of pemphigus vulgaris into pemphigus foliaceus: a reflection of changing desmoglein 1 and 3 autoantibody levels in pemphigus vulgaris Br J Dermatol 146 2002 684 687
15. M. Amagai, S. Karpati, R. Prussick, V. Klaus-Kovtun, and J.R. Stanley Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic J Clin Invest 90 1992 919 926
16. M. Amagai, T. Hashimoto, N. Shimizu, and T. Nishikawa Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus J Clin Invest 94 1994 59 67
17. M. Amagai, T. Hashimoto, K.J. Green, N. Shimizu, and T. Nishikawa Antigen-specific immunoabsorption of pathogenic autoantibodies in pemphigus foliaceus J Invest Dermatol 104 1995 895 901
18. X. Ding, L.A. Diaz, J.A. Fairley, G.J. Guidice, and Z. Liu The anti-desmoglein 1 autoantibodies in pemphigus vulgaris sera are pathogenic J Invest Dermatol 112 1999 739 743
19. Y. Shirakata, M. Amagai, Y. Hanakawa, T. Nishikawa, and K. Hashimoto Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1 J Invest Dermatol 110 1998 76 78
20. M.G. Mahoney, Z.W. Wang, K. Rothenberger, P.J. Koch, M. Amagai, and J.R. Stanley Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris J Clin Invest 103 1999 461 468
21. H. Shimizu, T. Masunaga, A. Ishiko, A. Kikuchi, T. Hashimoto, and T. Nishikawa Pemphigus vulgaris and pemphigus foliaceus sera show an inversely graded binding pattern to extracellular regions of desmosomes in different layers of human epidermis J Invest Dermatol 105 1995 153 159
22. M. Amagai, P.J. Koch, T. Nishikawa, and J.R. Stanley Pemphigus vulgaris antigen (desmoglein 3) is localized in the lower epidermis, the site of blister formation in patients J Invest Dermatol 106 1996 351 355
23. H. Wu, Z.H. Wang, A. Yan, S. Lyle, S. Fakharzadeh, J.K. Wahl, M.J. Wheelock, H. Ishikawa, J. Uitto, and M. Amagai Protection against pemphigus foliaceus by desmoglein 3 in neonates N Engl J Med 343 2000 31 35
24. P.J. Koch, M.G. Mahoney, H. Ishikawa, L. Pulkkinen, J. Uitto, L. Shultz, G.F. Murphy, D. Whitaker-Menezes, and J.R. Stanley Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris J Cell Biol 137 1997 1091 1102
25. bal-Pas mice with homozygous deletion mutation (2079del14) in the desmoglein 3 gene J Invest Dermatol 119 2002 1237 1243
26. P.J. Koch, M.G. Mahoney, G. Cotsarelis, K. Rothenberger, R.M. Lavker, and J.R. Stanley Desmoglein 3 anchors telogen hair in the follicle J Cell Sci 111 1998 2529 2537
27. M. Amagai, K. Tsunoda, H. Suzuki, K. Nishifuji, S. Koyasu, and T. Nishikawa Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus J Clin Invest 105 2000 625 631
28. -/- immunodeficient mice that express Dsg3. This model of active disease allows the study of immunological mechanisms of autoimmunity.
29. M. Ohyama, M. Amagai, K. Tsunoda, T. Ota, S. Koyasu, J. Hata, A. Umezawa, and T. Nishikawa Immunologic and histopathologic characterization of an active disease mouse model for pemphigus vulgaris J Invest Dermatol 118 2002 199 204
30. A. Shimizu, A. Ishiko, T. Ota, K. Tsunoda, T. Ota, S. Koyasu, M. Amagai, and T. Nishikawa Ultrastructural changes in mice actively producing antibodies to desmoglein 3 parallel those in patients with pemphigus vulgaris Arch Dermatol Res 294 2002 318 323
31. K. Tsunoda, T. Ota, H. Suzuki, M. Ohyama, T. Nagai, T. Nishikawa, M. Amagai, and S. Koyasu Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris Eur J Immunol 32 2002 627 633
32. K. Tsunoda, T. Ota, M. Aoki, T. Yamada, T. Nagai, T. Nakagawa, S. Koyasu, T. Nishikawa, and M. Amagai Induction of pemphigus phenotype by a mouse monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3 J Immunol 170 2003 2170 2178 Anti-Dsg3 IgG monoclonal antibodies (mAbs) are isolated from the active disease mouse model of pemphigus. The AK23 pathogenic mAb recognizes four specific residues in the N-terminal adhesive interface of Dsg3, while other mAbs that do not produce disease bind Dsg3 at middle to membrane-proximal sites within the extracellular domain. These findings suggest that direct inhibition of Dsg3 adhesion is the initial molecular event in blister formation in pemphigus.
33. M. Amagai Desmoglein as a target in autoimmunity and infection J Am Acad Dermatol 48 2003 244 252
34. C.Y. Lee, J.J. Schmidt, A.D. Johnson-Winegar, L. Spero, and J.J. Iandolo Sequence determination and comparison of the exfoliative toxin A and toxin B genes from Staphylococcus aureus J Bacteriol 169 1987 3904 3909
35. T. Yamaguchi, K. Nishifuji, M. Sasaki, Y. Fudaba, M. Aepfelbacher, T. Takata, M. Ohara, H. Komatsuzawa, M. Amagai, and M. Sugai Identification of the Staphylococcus aureus etd pathogenicity island which encodes a novel exfoliative toxin, ETD, and EDIN-B Infect Immun 70 2002 5835 5845
36. G.M. Vath, C.A. Earhart, J.V. Rago, M.H. Kim, G.A. Bohach, P.M. Schlievert, and D.H. Ohlendorf The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease Biochemistry 36 1997 1559 1566
37. G.M. Vath, C.A. Earhart, D.D. Monie, J.J. Iandolo, P.M. Schlievert, and D.H. Ohlendorf The crystal structure of exfoliative toxin B: a superantigen with enzymatic activity Biochemistry 38 1999 10239 10246
38. M. Amagai, N. Matsuyoshi, Z.H. Wang, C.D. Andl, and J.R. Stanley Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein I Nat Med 6 2000 1275 1277
39. M. Amagai, T. Yamaguchi, Y. Hanakawa, K. Nishifuji, M. Sugai, and J.R. Stanley Staphylococcal exfoliative toxin B specifically cleaves desmoglein I J Invest Dermatol 118 2002 845 850
40. Y. Hanakawa, N.M. Schechter, C. Lin, L. Garza, H. Li, T. Yamaguchi, Y. Fudaba, K. Nishifuji, M. Sugai, and M. Amagai Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome J Clin Invest 110 2002 53 60
41. Y. Hanakawa, N.M. Schechter, C. Lin, K. Nishifuji, M. Amagai, and J.R. Stanley Enzymatic and molecular characteristics of the efficiency and specificity of exfoliative toxin cleavage of desmoglein 1 J Biol Chem 279 2004 5268 5277 ET binds but does not cleave canine Dsg1. Substitution of five amino acid residues from human Dsg1 100 amino acid residues upstream of the scissile bond allows proteolysis. These data, together with the lack of ET inhibition by classic serine protease inhibitors, suggest that the fastidious enzymatic specificity of ET may be because activation of the catalytic site requires binding to a specific substrate conformation.
42. Y. Hanakawa, T. Selwood, D. Woo, C. Lin, N.M. Schechter, and J.R. Stanley Calcium-dependent conformation of desmoglein 1 is required for its cleavage by exfoliative toxin J Invest Dermatol 121 2003 383 389
43. L. Shapiro, A.M. Fannon, P.D. Kwong, A. Thompson, M.S. Lehmann, G. Grubel, J.F. Legrand, J. Als-Nielsen, D.R. Colman, and W.A. Hendrickson Structural basis of cell-cell adhesion by cadherins Nature 374 1995 327 337
44. B. Nagar, M. Overduin, M. Ikura, and J.M. Rini Structural basis of calcium-induced E-cadherin rigidification and dimerization Nature 380 1996
45. T.J. Boggon, J. Murray, S. Chappuis-Flament, E. Wong, B.M. Gumbiner, and L. Shapiro C-cadherin ectodomain structure and implications for cell adhesion mechanisms Science 296 2002 1308 1313 The solution structure of the C-cadherin ectodomain suggests a curved rod-like structure stabilized by calcium binding between the extracellular subdomains, with residues in ectodomain 1 comprising the trans adhesive interface.
46. A.P. Kowalczyk, J.E. Anderson, J.E. Borgwardt, T. Hashimoto, J.R. Stanley, and K.J. Green Pemphigus sera recognize conformationally sensitive epitopes in the amino-terminal region of desmoglein-1 (Dsg1) J Invest Dermatol 105 1995 147 152
47. M. Amagai, K. Ishii, T. Hashimoto, S. Gamou, N. Shimizu, and T. Nishikawa Conformational epitopes of pemphigus antigens (Dsg1 and Dsg3) are calcium-dependent and glycosylation-independent J Invest Dermatol 105 1995 243 247
48. Y. Futei, M. Amagai, M. Sekiguchi, K. Nishifuji, Y. Fujii, and T. Nishikawa Use of domain-swapped molecules for conformational epitope mapping of desmoglein 3 in pemphigus vulgaris J Invest Dermatol 115 2000 829 834
49. N. Li, V. Aoki, G. Hans-Filho, E.A. Rivitti, and L.A. Diaz The role of intramolecular epitope spreading in the pathogenesis of endemic pemphigus foliaceus (fogo selvagem) J Exp Med 197 2003 1501 1510 Epitope mapping of sera from a Brazilian endemic form of PF known as fogo selvagem (FS) shows that sera from FS patients in the preclinical stage or in remission recognize epitopes in EC5 domain of Dsg1, while sera from patients with active disease bind epitopes in EC1 and EC2.
50. M.K. Hacker-Foegen, M. Janson, M. Amagai, J.A. Fairley, and M.S. Lin Pathogenicity and epitope characteristics of anti-desmoglein-1 from pemphigus foliaceus patients expressing only IgG1 autoantibodies J Invest Dermatol 121 2003 1373 1378
51. M. Sekiguchi, Y. Futei, Y. Fujii, T. Iwasaki, T. Nishikawa, and M. Amagai Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive region of desmogleins J Immunol 167 2001 5439 5448
52. R. Caldelari, A. de Bruin, D. Baumann, M.M. Suter, C. Bierkamp, V. Balmer, and E. Müller A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris J Cell Biol 153 2001 823 834
53. Y. Aoyama, M.K. Owada, and Y. Kitajima A pathogenic autoantibody, pemphigus vulgaris-IgG, induces phosphorylation of desmoglein 3, and its dissociation from plakoglobin in cultured keratinocytes Eur J Immunol 29 1999 2233 2240
54. C.D. Andl, and J.R. Stanley Central role of the plakoglobin-binding domain for desmoglein 3 incorporation into desmosomes J Invest Dermatol 117 2001 1068 1074
55. Y. Aoyama, and Y. Kitajima Pemphigus vulgaris-IgG causes a rapid depletion of desmoglein 3 (Dsg3) from the triton X-100 soluble pools, leading to the formation of Dsg3-depleted desmosomes in human squamous carcinoma cell line, DJM-1 cells J Invest Dermatol 112 1999 67 71
56. A. Shimizu, A. Ishiko, T. Ota, K. Tsunoda, M. Amagai, and T. Nishikawa IgG binds to desmoglein 3 in desmosomes and causes a desmosomal split without keratin retraction in a pemphigus mouse model J Invest Dermatol 122 2004 1145 1153 Post-embedding immunoelectron microscopy studies of mucosal erosions from the pemphigus mouse model demonstrate that split desmosomes still contain Dsg3 and that keratin filaments are still attached to the desmosomal plaque at this stage, suggesting that the dissociation of half desmosomes is the initial event in PV IgG-induced acantholysis, with keratin retraction and Dsg3 depletion from the desmosome occurring as later events.
57. A. Kljuic, H. Bazzi, J.P. Sundberg, M.G. Mahoney, M. Levy, X. Montagutelli, W. Ahmad, V.M. Aita, D. Gordon, and J. Uitto Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris Cell 113 2003 249 260 The authors identify a novel desmosomal cadherin, Dsg4, which is expressed in the suprabasal epidermis and anagen hair follicle and appears to play a role in the differentiation of hair matrix keratinocytes. Electron microscopy of mouse epidermis lacking Dsg4 expression demonstrates poorly formed desmosomes with scant keratin filament insertion and points of intracellular detachment. This study highlights the importance of cellular adhesion to the activation of appropriate differentiation programs within hair follicle keratinocytes. Although some PV sera were shown to bind Dsg4, the role of Dsg4 in PV remains to be determined.
58. D.L. Swanson, and M.V. Dahl Methlyprednisolone inhibits pemphigus acantholysis in skin cultures J Invest Dermatol 81 1983 258 260
59. E.W. Jeffes, R.P. Kaplan, and A.R. Ahmed Acantholysis produced in vitro with pemphigus serum hydrocortisone inhibits acantholysis, while dapsone and 6-mercaptopurine do not inhibit acantholysis J Clin Immunol 4 1984 359 363
60. V.T. Nguyen, J. Arredondo, A.I. Chernyavsky, Y. Kitajima, M. Pittelkow, and S.A. Grando Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on keratinocytes J Biol Chem 279 2004 2135 2146 Gene expression analysis of cultured keratinocytes treated with PV IgG, either alone or following pretreatment with methylprednisolone (MP), demonstrates down-regulation of adhesion molecules such as E-cadherin, Dsg1 and Dsg3 in response to PV IgG and up-regulation of these molecules with MP. MP abrogates PV IgG-induced phosphorylation of desmosomal proteins, suggesting that the therapeutic effects of corticosteroids in pemphigus are not solely immunomodulatory.
61. J.N. Mehta, and A.G. Martin A case of pemphigus vulgaris improved by cigarette smoking Arch Dermatol 136 2000 15 17
62. V.T. Nguyen, J. Arredondo, A.I. Chernyavsky, M.R. Pittelkow, Y. Kitajima, and S.A. Grando Pemphigus vulgaris acantholysis ameliorated by cholinergic agonists Arch Dermatol 140 2004 327 334
63. V.T. Nguyen, A.I. Chernyavsky, J. Arredondo, D. Bercovich, A. Orr-Urtreger, D.E. Vetter, J. Wess, A.L. Beaudet, Y. Kitajima, and S.A. Grando Synergistic control of keratinocyte adhesion through muscarinic and nicotinic acetylcholine receptor subtypes Exp Cell Res 294 2004 534 549