BP180的生物学功能与相关疾病研究进展
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摘要
BP180(大疱性类天疱疮抗原2)又称胶原蛋白ⅩⅤⅡ,是半桥粒蛋白中的重要组成成分,在维持真表皮交界处紧密连接中发挥重要作用。近年来发现BP180可能存在其他的生物学功能。本文对BP180的结构、生物学功能及相关疾病发病机制的新进展做一综述。
BP180( bullous pemphigoid antigen 2,BPAG2),also known as collagen ⅩⅤⅡ,is an important hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. In recent years,it has been found that BP180 may have other biological functions. In this paper,we reviewed the updates of the structure,functions and the mechanisms in BP180-associated diseases.
BP180( bullous pemphigoid antigen 2,BPAG2),also known as collagen ⅩⅤⅡ,is an important hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. In recent years,it has been found that BP180 may have other biological functions. In this paper,we reviewed the updates of the structure,functions and the mechanisms in BP180-associated diseases.
引文
[1]Franzke CW,Tasanen K,Schumann H,et al.Collagenous transmembrane proteins:collagen XVII as a prototype[J].Matrix Biol,2003,22(4):299-309.
[2]Has C,Kern JS.Collagen XVII[J].Dermatol Clin,2010,28(1):61-66.
[3]Intong LR,Murrell DF.Inherited epidermolysis bullosa:new diagnostic criteria and classification[J].Clin Dermatol,2012,30(1):70-77.
[4]Schmidt E,Zillikens D.Pemphigoid diseases[J].Lancet,2013,381(9863):320-332.
[5]Zimina EP,Fritsch A,Schermer B,et al.Extracellular phosphorylation of collagen XVII by ecto-casein kinase 2 inhibits ectodomain shedding[J].J Biol Chem,2007,282(31):22737-22746.
[6]Uitto J,Richard G.Progress in epidermolysis bullosa:from eponyms to molecular genetic classification[J].Clin Dermatol,2005,23(1):33-40.
[7]Van den Bergh F,Fu CL,Olague-Marchan M,et al.The NC16Adomain of collagen XVII plays a role in triple helix assembly and stability[J].Biochem Biophys Res Commun,2006,350(4):1032-1037.
[8]Franzke CW,Bruckner P,Bruckner-Tuderman L.Collagenous transmembrane proteins:recent insights into biology and pathology[J].J Biol Chem,2005,280(6):4005-4008.
[9]Franzke CW,Tasanen K,Schacke H,et al.Transmembrane collagen XVII,an epithelial adhesion protein,is shed from the cell surface by ADAMs[J].Embo J,2002,21(19):5026-5035.
[10]Nykvist P,Tasanen K,Viitasalo T,et al.The cell adhesion domain of type XVII collagen promotes integrin-mediated cell spreading by a novel mechanism[J].J Biol Chem,2001,276(42):38673-38679.
[11]Bauer JW,Lanschuetzer C.Type XVII collagen gene mutations in junctional epidermolysis bullosa and prospects for gene therapy[J].Clin Exp Dermatol,2003,28(1):53-60.
[12]Bagci IS,Horvath ON,Ruzicka T,et al.Bullous pemphigoid[J].Autoimmun Rev,2017,16(5):445-455.
[13]Pulkkinen L,Ringpfeil F,Uitto J.Progress in heritable skin diseases:molecular bases and clinical implications[J].J Am Acad Dermatol,2002,47(1):91-104.
[14]Sproule TJ,Bubier JA,Grandi FC,et al.Molecular identification of collagen 17a1 as a major genetic modifier of laminin gamma 2mutation-induced junctional epidermolysis bullosa in mice[J].PLo S Genet,2014,10(2):e1004068.
[15]Tasanen K,Floeth M,Schumann H,et al.Hemizygosity for a glycine substitution in collagen XVII:unfolding and degradation of the ectodomain[J].J Invest Dermatol,2000,115(2):207-212.
[16]Natsuga K,Shinkuma S,Nishie W,et al.Animal models of epidermolysis bullosa[J].Dermatol Clin,2010,28(1):137-142.
[17]Hurskainen T,Kokkonen N,Sormunen R,et al.Deletion of the major bullous pemphigoid epitope region of collagen XVII induces blistering,autoimmunization,and itching in mice[J].J Invest Dermatol,2015,135(5):1303-1310.
[18]Zhang Y,Hwang BJ,Liu Z,et al.BP180 dysfunction triggers spontaneous skin inflammation in mice[J].Expert Rer Clin Immunol,2018,115(25):6434-6439.
[19]van Beek N,Schulze FS,Zillikens D,et al.Ig E-mediated mechanisms in bullous pemphigoid and other autoimmune bullous diseases[J].Expert Rev Clin Immunol,2016,12(3):267-277.
[20]Bieber K,Sun S,Ishii N,et al.Animal models for autoimmune bullous dermatoses[J].Exp Dermatol,2010,19(1):2-11.
[21]Zillikens D.BP180 as the common autoantigen in blistering diseases with different clinical phenotypes[J].Keio J Med,2002,51(1):21-28.
[22]Chen R,Ning G,Zhao ML,et al.Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid[J].JClin Invest,2001,108(8):1151-1158.
[23]Kromminga A,Scheckenbach C,Georgi M,et al.Patients with bullous pemphigoid and linear Ig A disease show a dual Ig A and Ig Gautoimmune response to BP180[J].J Autoimmun,2000,15(3):293-300.
[24]Zone JJ,Egan CA,Taylor TB,et al.Ig A autoimmune disorders:development of a passive transfer mouse model[J].J Investig Dermatol Symp Proc,2004,9(1):47-51.
[25]Intong LR,Murrell DF.Pemphigoid gestationis:pathogenesis and clinical features[J].Dermatol Clin,2011,29(3):447-452,ix.
[26]Powell AM,Sakuma-Oyama Y,Oyama N,et al.Usefulness of BP180 NC16 a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy[J].Arch Dermatol,2005,141(6):705-710.
[27]Oyama N,Setterfield JF,Powell AM,et al.Bullous pemphigoid antigen II(BP180)and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid:the pathogenic relevance to HLA class II alleles and disease severity[J].Br J Dermatol,2006,154(1):90-98.
[28]Rashid KA,Gurcan HM,Ahmed AR.Antigen specificity in subsets of mucous membrane pemphigoid[J].J Invest Dermatol,2006,126(12):2631-2636.
[29]Egan CA,Lazarova Z,Darling TN,et al.Anti-epiligrin cicatricial pemphigoid and relative risk for cancer[J].Lancet,2001,357(9271):1850-1851.
[30]Lazarova Z,Hsu R,Yee C,et al.Human anti-laminin 5 autoantibodies induce subepidermal blisters in an experimental human skin graft model[J].J Invest Dermatol,2000,114(1):178-184.
[31]Lazarova Z,Hsu R,Briggaman RA,et al.Fab fragments directed against laminin 5 induce subepidermal blisters in neonatal mice[J].Clin Immunol,2000,95(1 Pt 1):26-32.
[32]Rashid KA,Stern JN,Ahmed AR.Identification of an epitope within human integrin alpha 6 subunit for the binding of autoantibody and its role in basement membrane separation in oral pemphigoid[J].J Immunol,2006,176(3):1968-1977.
[33]Saw VP,Offiah I,Dart RJ,et al.Conjunctival interleukin-13 expression in mucous membrane pemphigoid and functional effects of interleukin-13 on conjunctival fibroblasts in vitro[J].Am JPathol,2009,175(6):2406-2415.
[34]Chen YJ,Wu CY,Lin MW,et al.Comorbidity profiles among patients with bullous pemphigoid:a nationwide population-based study[J].Br J Dermatol,2011,165(3):593-599.
[35]Jeffe JS,Seshadri S,Hamill KJ,et al.A role for anti-BP180 autoantibodies in chronic rhinosinusitis[J].Laryngoscope,2013,123(9):2104-2111.
[36]Amber KT,Murrell DF,Schmidt E,et al.Autoimmune subepidermal bullous diseases of the skin and mucosae:clinical features,diagnosis,and management[J].Clin Rev Allergy Immunol,2018,54(1):26-51.
[37]Snauwaert JJ,Yuen WY,Jonkman MF,et al.Burden of itch in epidermolysis bullosa[J].Br J Dermatol,2014,171(1):73-78.
[38]Rossbach K,Schaper K,Kloth C,et al.Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis[J].Allergy,2016,71(2):189-197.
[39]Saunders SP,Moran T,Floudas A,et al.Spontaneous atopic dermatitis is mediated by innate immunity,with the secondary lung inflammation of the atopic march requiring adaptive immunity[J].JAllergy Clin Immunol,2016,137(2):482-491.
[40]Cork MJ,Danby SG,Vasilopoulos Y,et al.Epidermal barrier dysfunction in atopic dermatitis[J].J Invest Dermatol,2009,129(8):1892-1908.
[41]Stemmler S,Parwez Q,Petrasch-Parwez E,et al.Association of variation in the LAMA3 gene,encoding the alpha-chain of laminin5,with atopic dermatitis in a German case-control cohort[J].BMC Dermatol,2014,14(1):17.
[42]Messingham KAN,Aust S,Helfenberger J,et al.Autoantibodies to collagen XVII are present in parkinson's disease and localize to Tyrosine-Hydroxylase positive neurons[J].J Invest Dermatol,2016,136(3):721-723.
[43]Khosravani S,Handjani F,Alimohammadi R,et al.Frequency of neurological disorders in bullous pemphigoid patients:A cross-sectional study[J].Int Sch Res Notices,2017,5(24):6053267.
[44]Teixeira VB,Cabral R,Brites MM,et al.Bullous pemphigoid and comorbidities:a case-control study in Portuguese patients[J].An Bras Dermatol,2014,89(2):274-278.
[45]王菂.脑卒中患者体内BP抗体水平与大疱性类天疱疱患者认知功能研究[D].北京协和医学院,2015.
[46]Bech R,Kibsgaard L,Vestergaard C.Comorbidities and treatment strategies in bullous pemphigoid:An appraisal of the existing litterature[J].Front Med(Lausanne),2018,5(3):238.
[47]王亚如,李洪军,许德志,等.131例神经系统疾病患者血清中抗BP180和抗BP230抗体的检测[J].中国麻风皮肤病杂志,2018,34(5):257-260,264.
[48]Gambichler T,Segert H,Hoxtermann S,et al.Neurological disorders in patients with bullous pemphigoid:clinical and experimental investigations[J].J Eur Acad Dermatol Venereol,2015,29(9):1758-1762.
[49]Gornowicz-Porowska J,Seraszek-Jaros A,Bowszyc-Dmochowska M,et al.Analysis of the autoimmune response against BP180 and BP230 in ethnic Poles with neurodegenerative disorders and bullous pemphigoid[J].Cent Eur J Immunol,2017,42(1):85-90.
[50]Taghipour K,Chi CC,Bhogal B,et al.Immunopathological characteristics of patients with bullous pemphigoid and neurological disease[J].J Eur Acad Dermatol Venereol,2014,28(5):569-573.
[51]Parikka M,Nissinen L,Kainulainen T,et al.Collagen XVII promotes integrin-mediated squamous cell carcinoma transmigration-a novel role for alphaIIb integrin and tirofiban[J].Exp Cell Res,2006,312(8):1431-1438.
[52]Krenacs T,Kiszner G,Stelkovics E,et al.Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis[J].Histochem Cell Biol,2012,138(4):653-667.
[53]Amber KT,Panganiban CM,Korta D,et al.A case report of bullous pemphigoid associated with a melanoma and review of the literature[J].Melanoma Res,2017,27(1):65-67.
[54]Shimbo T,Tanemura A,Yamazaki T,et al.Serum anti-BPAG1auto-antibody is a novel marker for human melanoma[J].PLo SOne,2010,5(5):e10566.
[55]Marks JM.Pemphigoid with malignant melanoma[J].Proc R Soc Med,1961,54(3):225-226.
[56]Fine JD,Johnson LB,Weiner M,et al.Epidermolysis bullosa and the risk of life-threatening cancers:the National EB Registry experience,1986-2006[J].J Am Acad Dermatol,2009,60(2):203-211.
[2]Has C,Kern JS.Collagen XVII[J].Dermatol Clin,2010,28(1):61-66.
[3]Intong LR,Murrell DF.Inherited epidermolysis bullosa:new diagnostic criteria and classification[J].Clin Dermatol,2012,30(1):70-77.
[4]Schmidt E,Zillikens D.Pemphigoid diseases[J].Lancet,2013,381(9863):320-332.
[5]Zimina EP,Fritsch A,Schermer B,et al.Extracellular phosphorylation of collagen XVII by ecto-casein kinase 2 inhibits ectodomain shedding[J].J Biol Chem,2007,282(31):22737-22746.
[6]Uitto J,Richard G.Progress in epidermolysis bullosa:from eponyms to molecular genetic classification[J].Clin Dermatol,2005,23(1):33-40.
[7]Van den Bergh F,Fu CL,Olague-Marchan M,et al.The NC16Adomain of collagen XVII plays a role in triple helix assembly and stability[J].Biochem Biophys Res Commun,2006,350(4):1032-1037.
[8]Franzke CW,Bruckner P,Bruckner-Tuderman L.Collagenous transmembrane proteins:recent insights into biology and pathology[J].J Biol Chem,2005,280(6):4005-4008.
[9]Franzke CW,Tasanen K,Schacke H,et al.Transmembrane collagen XVII,an epithelial adhesion protein,is shed from the cell surface by ADAMs[J].Embo J,2002,21(19):5026-5035.
[10]Nykvist P,Tasanen K,Viitasalo T,et al.The cell adhesion domain of type XVII collagen promotes integrin-mediated cell spreading by a novel mechanism[J].J Biol Chem,2001,276(42):38673-38679.
[11]Bauer JW,Lanschuetzer C.Type XVII collagen gene mutations in junctional epidermolysis bullosa and prospects for gene therapy[J].Clin Exp Dermatol,2003,28(1):53-60.
[12]Bagci IS,Horvath ON,Ruzicka T,et al.Bullous pemphigoid[J].Autoimmun Rev,2017,16(5):445-455.
[13]Pulkkinen L,Ringpfeil F,Uitto J.Progress in heritable skin diseases:molecular bases and clinical implications[J].J Am Acad Dermatol,2002,47(1):91-104.
[14]Sproule TJ,Bubier JA,Grandi FC,et al.Molecular identification of collagen 17a1 as a major genetic modifier of laminin gamma 2mutation-induced junctional epidermolysis bullosa in mice[J].PLo S Genet,2014,10(2):e1004068.
[15]Tasanen K,Floeth M,Schumann H,et al.Hemizygosity for a glycine substitution in collagen XVII:unfolding and degradation of the ectodomain[J].J Invest Dermatol,2000,115(2):207-212.
[16]Natsuga K,Shinkuma S,Nishie W,et al.Animal models of epidermolysis bullosa[J].Dermatol Clin,2010,28(1):137-142.
[17]Hurskainen T,Kokkonen N,Sormunen R,et al.Deletion of the major bullous pemphigoid epitope region of collagen XVII induces blistering,autoimmunization,and itching in mice[J].J Invest Dermatol,2015,135(5):1303-1310.
[18]Zhang Y,Hwang BJ,Liu Z,et al.BP180 dysfunction triggers spontaneous skin inflammation in mice[J].Expert Rer Clin Immunol,2018,115(25):6434-6439.
[19]van Beek N,Schulze FS,Zillikens D,et al.Ig E-mediated mechanisms in bullous pemphigoid and other autoimmune bullous diseases[J].Expert Rev Clin Immunol,2016,12(3):267-277.
[20]Bieber K,Sun S,Ishii N,et al.Animal models for autoimmune bullous dermatoses[J].Exp Dermatol,2010,19(1):2-11.
[21]Zillikens D.BP180 as the common autoantigen in blistering diseases with different clinical phenotypes[J].Keio J Med,2002,51(1):21-28.
[22]Chen R,Ning G,Zhao ML,et al.Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid[J].JClin Invest,2001,108(8):1151-1158.
[23]Kromminga A,Scheckenbach C,Georgi M,et al.Patients with bullous pemphigoid and linear Ig A disease show a dual Ig A and Ig Gautoimmune response to BP180[J].J Autoimmun,2000,15(3):293-300.
[24]Zone JJ,Egan CA,Taylor TB,et al.Ig A autoimmune disorders:development of a passive transfer mouse model[J].J Investig Dermatol Symp Proc,2004,9(1):47-51.
[25]Intong LR,Murrell DF.Pemphigoid gestationis:pathogenesis and clinical features[J].Dermatol Clin,2011,29(3):447-452,ix.
[26]Powell AM,Sakuma-Oyama Y,Oyama N,et al.Usefulness of BP180 NC16 a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy[J].Arch Dermatol,2005,141(6):705-710.
[27]Oyama N,Setterfield JF,Powell AM,et al.Bullous pemphigoid antigen II(BP180)and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid:the pathogenic relevance to HLA class II alleles and disease severity[J].Br J Dermatol,2006,154(1):90-98.
[28]Rashid KA,Gurcan HM,Ahmed AR.Antigen specificity in subsets of mucous membrane pemphigoid[J].J Invest Dermatol,2006,126(12):2631-2636.
[29]Egan CA,Lazarova Z,Darling TN,et al.Anti-epiligrin cicatricial pemphigoid and relative risk for cancer[J].Lancet,2001,357(9271):1850-1851.
[30]Lazarova Z,Hsu R,Yee C,et al.Human anti-laminin 5 autoantibodies induce subepidermal blisters in an experimental human skin graft model[J].J Invest Dermatol,2000,114(1):178-184.
[31]Lazarova Z,Hsu R,Briggaman RA,et al.Fab fragments directed against laminin 5 induce subepidermal blisters in neonatal mice[J].Clin Immunol,2000,95(1 Pt 1):26-32.
[32]Rashid KA,Stern JN,Ahmed AR.Identification of an epitope within human integrin alpha 6 subunit for the binding of autoantibody and its role in basement membrane separation in oral pemphigoid[J].J Immunol,2006,176(3):1968-1977.
[33]Saw VP,Offiah I,Dart RJ,et al.Conjunctival interleukin-13 expression in mucous membrane pemphigoid and functional effects of interleukin-13 on conjunctival fibroblasts in vitro[J].Am JPathol,2009,175(6):2406-2415.
[34]Chen YJ,Wu CY,Lin MW,et al.Comorbidity profiles among patients with bullous pemphigoid:a nationwide population-based study[J].Br J Dermatol,2011,165(3):593-599.
[35]Jeffe JS,Seshadri S,Hamill KJ,et al.A role for anti-BP180 autoantibodies in chronic rhinosinusitis[J].Laryngoscope,2013,123(9):2104-2111.
[36]Amber KT,Murrell DF,Schmidt E,et al.Autoimmune subepidermal bullous diseases of the skin and mucosae:clinical features,diagnosis,and management[J].Clin Rev Allergy Immunol,2018,54(1):26-51.
[37]Snauwaert JJ,Yuen WY,Jonkman MF,et al.Burden of itch in epidermolysis bullosa[J].Br J Dermatol,2014,171(1):73-78.
[38]Rossbach K,Schaper K,Kloth C,et al.Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis[J].Allergy,2016,71(2):189-197.
[39]Saunders SP,Moran T,Floudas A,et al.Spontaneous atopic dermatitis is mediated by innate immunity,with the secondary lung inflammation of the atopic march requiring adaptive immunity[J].JAllergy Clin Immunol,2016,137(2):482-491.
[40]Cork MJ,Danby SG,Vasilopoulos Y,et al.Epidermal barrier dysfunction in atopic dermatitis[J].J Invest Dermatol,2009,129(8):1892-1908.
[41]Stemmler S,Parwez Q,Petrasch-Parwez E,et al.Association of variation in the LAMA3 gene,encoding the alpha-chain of laminin5,with atopic dermatitis in a German case-control cohort[J].BMC Dermatol,2014,14(1):17.
[42]Messingham KAN,Aust S,Helfenberger J,et al.Autoantibodies to collagen XVII are present in parkinson's disease and localize to Tyrosine-Hydroxylase positive neurons[J].J Invest Dermatol,2016,136(3):721-723.
[43]Khosravani S,Handjani F,Alimohammadi R,et al.Frequency of neurological disorders in bullous pemphigoid patients:A cross-sectional study[J].Int Sch Res Notices,2017,5(24):6053267.
[44]Teixeira VB,Cabral R,Brites MM,et al.Bullous pemphigoid and comorbidities:a case-control study in Portuguese patients[J].An Bras Dermatol,2014,89(2):274-278.
[45]王菂.脑卒中患者体内BP抗体水平与大疱性类天疱疱患者认知功能研究[D].北京协和医学院,2015.
[46]Bech R,Kibsgaard L,Vestergaard C.Comorbidities and treatment strategies in bullous pemphigoid:An appraisal of the existing litterature[J].Front Med(Lausanne),2018,5(3):238.
[47]王亚如,李洪军,许德志,等.131例神经系统疾病患者血清中抗BP180和抗BP230抗体的检测[J].中国麻风皮肤病杂志,2018,34(5):257-260,264.
[48]Gambichler T,Segert H,Hoxtermann S,et al.Neurological disorders in patients with bullous pemphigoid:clinical and experimental investigations[J].J Eur Acad Dermatol Venereol,2015,29(9):1758-1762.
[49]Gornowicz-Porowska J,Seraszek-Jaros A,Bowszyc-Dmochowska M,et al.Analysis of the autoimmune response against BP180 and BP230 in ethnic Poles with neurodegenerative disorders and bullous pemphigoid[J].Cent Eur J Immunol,2017,42(1):85-90.
[50]Taghipour K,Chi CC,Bhogal B,et al.Immunopathological characteristics of patients with bullous pemphigoid and neurological disease[J].J Eur Acad Dermatol Venereol,2014,28(5):569-573.
[51]Parikka M,Nissinen L,Kainulainen T,et al.Collagen XVII promotes integrin-mediated squamous cell carcinoma transmigration-a novel role for alphaIIb integrin and tirofiban[J].Exp Cell Res,2006,312(8):1431-1438.
[52]Krenacs T,Kiszner G,Stelkovics E,et al.Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis[J].Histochem Cell Biol,2012,138(4):653-667.
[53]Amber KT,Panganiban CM,Korta D,et al.A case report of bullous pemphigoid associated with a melanoma and review of the literature[J].Melanoma Res,2017,27(1):65-67.
[54]Shimbo T,Tanemura A,Yamazaki T,et al.Serum anti-BPAG1auto-antibody is a novel marker for human melanoma[J].PLo SOne,2010,5(5):e10566.
[55]Marks JM.Pemphigoid with malignant melanoma[J].Proc R Soc Med,1961,54(3):225-226.
[56]Fine JD,Johnson LB,Weiner M,et al.Epidermolysis bullosa and the risk of life-threatening cancers:the National EB Registry experience,1986-2006[J].J Am Acad Dermatol,2009,60(2):203-211.