RESUMO
BACKGROUND: Nagashima-type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss-of-function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK. OBJECTIVES: To confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK. METHODS: We analysed 10 Japanese families with NPPK using Sanger and/or whole-exome sequencing. RESULTS: We identified one novel and three recurrent null mutations in SERPINB7. In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK. CONCLUSIONS: These data clearly provide further evidence that NPPK is caused by loss-of-function mutations in SERPINB7.
Assuntos
Efeito Fundador , Genes Dominantes/genética , Ceratodermia Palmar e Plantar/genética , Serpinas/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Heterozigoto , Homozigoto , Humanos , Lactente , Padrões de Herança , Masculino , Pessoa de Meia-Idade , LinhagemAssuntos
Penfigoide Bolhoso/diagnóstico , Pele/patologia , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Biópsia , Distonina/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/patologia , Colágeno Tipo XVIIAssuntos
Autoanticorpos/metabolismo , Mucosa Bucal/imunologia , Penfigoide Mucomembranoso Benigno/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Autoantígenos/metabolismo , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Penfigoide Mucomembranoso Benigno/imunologiaAssuntos
Autoanticorpos/imunologia , Demência/complicações , Penfigoide Bolhoso/psicologia , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/imunologia , Autoantígenos/imunologia , Demência/imunologia , Distonina/imunologia , Feminino , Humanos , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Colágeno Tipo XVIIAssuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Feminino , Humanos , Masculino , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/imunologia , Pirazóis/efeitos adversos , Tiazolidinas/efeitos adversos , Fatores de Tempo , Vildagliptina/efeitos adversos , Colágeno Tipo XVIIRESUMO
Mucous membrane pemphigoid (MMP) is a mucous membrane-dominated, subepidermal autoimmune blistering disease in which autoantibodies usually react with the C-terminal domain of type XVII collagen (COL17) or with laminin-332. Only a few cases of MMP with widespread blisters have been reported. Serologically, IgA and IgG class autoantibodies directed against COL17 or IgG autoantibodies directed against laminin-332 in patients with MMP have been well documented. MMP cases in which IgA reacts with laminin-332, however, are extremely rare. We report a case of MMP in a 67-year-old man. Clinical examination revealed extensive mucosal lesions as well as generalized blisters and erosions that healed with scar formation. The disease was intractable to treatment with systemic steroids. Interestingly, in addition to IgG directed against laminin-332 and the noncollagenous 16A (NC16A) and C-terminal domains of COL17, circulating IgA reacting with laminin-332 and with the NC16A domain of COL17 was also detected. This is the first MMP case with circulating IgA and IgG autoantibodies against both laminin-332 and COL17.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Laminina/imunologia , Colágenos não Fibrilares/imunologia , Penfigoide Mucomembranoso Benigno/imunologia , Idoso , Vesícula/imunologia , Humanos , Immunoblotting , Masculino , Microscopia de Fluorescência , Colágeno Tipo XVIIAssuntos
Queratina-6/genética , Mutação , Paquioníquia Congênita/genética , Criança , Feminino , Humanos , Masculino , LinhagemRESUMO
BACKGROUND: Antilaminin-332 mucous membrane pemphigoid (MMP) is a chronic autoimmune bullous disease that is often associated with internal malignancy. IgG autoantibodies against laminin-332 in patients with MMP are well documented; however, IgA and IgE autoantibodies against laminin-332 have not yet been described. OBJECTIVES: To characterize IgA and IgE autoantibodies binding to laminin-332 in sera from patients with antilaminin-332 MMP. METHODS: Sera and skin samples from four patients who met the following criteria were used: (i) subepidermal blistering lesions present on the mucous membranes; (ii) in vivo deposition of IgG along the epidermal basement membrane zone of sampled skin; (iii) circulating IgG antibasement membrane zone antibodies that react with the dermal side of salt-split normal human skin; and (iv) circulating IgG autoantibodies that do not show positivity against type VII collagen or 200-kDa protein (p200 antigen) in immunoblot analysis using dermal extracts. Circulating IgG/IgA/IgE class autoantibodies against laminin-332 were determined by immunoblotting. RESULTS: Circulating IgG autoantibodies against the gamma2, alpha3/gamma2, alpha3 and alpha3/beta3/gamma2 subunits of laminin-332 were demonstrated in sera from four patients, respectively. Serum from one of the four patients showed IgA reactivity with the alpha3/beta3/gamma2 subunits of laminin-332. Serum from one of the four patients showed IgE reactivity with the gamma2 subunit of laminin-332. The control sera failed to display IgG/IgA/IgE reactivity to laminin-332. CONCLUSIONS: In addition to IgG autoantibodies, circulating IgA and IgE autoantibodies against laminin-332 are detectable in a subset of patients with antilaminin-332 MMP.