Biological predictors shared by dementia and bullous pemphigoid patients point out a cross-antigenicity between BP180/BP230 brain and skin isoforms

Autor(es)

Julio, Tamiris A. ^[1] ; Vernal, Sebastian ^[1] ; Massaro, Juliana D. ^[2] ; Silva, Matheus C. ^[2] ; Donadi, Eduardo A. ^[2] ; Moriguti, Julio C. ^[3] ; Roselino, Ana M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Clin Med, Div Dermatol, Ave Bandeirantes 3900, BR-14049900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Clin Med, Div Clin Immunol, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Dept Clin Med, Ribeirao Preto Med Sch, Div Gerontol, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: IMMUNOLOGIC RESEARCH; v. 66, n. 5, p. 567-576, OCT 2018.
• Citações Web of Science: 2

Resumo

Bullous pemphigoid (BP) following dementia diagnosis has been reported in the elderly. Skin and brain tissues express BP180 and BP230 isoforms. Dementia has been associated with rs6265 (Val66Met) polymorphism of the brain-derived neurotrophic factor (BDNF) gene and low serum BDNF. Here we investigated a possible cross-antigenicity between BP180/BP230 brain and skin isoforms. We assessed antibodies against BP180/BP230 and BDNF levels by ELISA and BDNF Val66Met SNP by PCR in three groups: 50 BP patients, 50 patients with dementia, and 50 elderly controls. Heatmap hierarchical clustering and data mining decision tree were used to analyze the patients' demographic and laboratorial data as predictors of dementia-BP association. Sixteen percent of BP patients with the lowest serological BDNF presented dementia-BP clinical association. Anti-BP180/230 positivity was unexpected observed among dementia patients (10%, 10%) and controls (14%, 1%). Indirect immunofluorescence using healthy human skin showed a BP pattern in two of 10 samples containing antibodies against BP180/BP230 obtained from dementia group but not in the control samples. Neither allelic nor genotypic BDNF Val66Met SNP was associated with dementia or with BP (associated or not with clinical manifestation of dementia). Heatmap analysis was able to differentiate the three studied groups and confirmed the ELISA results. The comprehensive data mining analysis revealed that BP patients and dementia patients shared biological predictors that justified the dementia-BP association. Autoantibodies against the BP180/BP230 brain isoforms produced by dementia patients could cross-react with the BP180/BP230 skin isoforms, which could justify cases of dementia preceding the BP disease. (AU)

• Processo FAPESP: 10/51729-2 - Relação dos fatores imunogenéticos e ambientais na etiopatogênese dos pênfigos em amostragem brasileira
• Beneficiário: Ana Maria Ferreira Roselino
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/09011-3 - Associação do penfigóide bolhoso com a demência: investigação do mimetismo molecular antigênico dos peptídeos hemidesmossomais da pele com peptídeos neuronais
• Beneficiário: Tamíris Amanda Júlio
• Modalidade de apoio: Bolsas no Brasil - Doutorado