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| Author(s): |
Tamiris Amanda Julio
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2020-10-06 |
| Examining board members: |
Ana Maria Ferreira Roselino;
Marilda Aparecida Milanez Morgado de Abreu;
Eduardo Ferriolli;
Vitor Tumas
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| Advisor: | Ana Maria Ferreira Roselino |
| Abstract | |
Autoantibodies against the hemidesmosomal proteins BP180 and/or BP230 cause bullous pemphigoid (BP). BP association with dementia in the elderly has been increasingly reported. Given (i) the presence of serum anti-BP180 and anti-BP230 in BP and dementia patients, (ii) anti-BP180 and anti-BP230 identification in the liquor of two BP patients with neurologic diseases, and (iii) rare reports on controversial BP180 and BP230 isoforms expression in the central nervous system (CNS), we evaluate neural and skin BP180 and BP230 molecular mimicry in in vitro assays with human keratinocytes (DJM-1) and astrocytes (TM-31). Immunofluorescence confirmed the 180-kDa expression in keratinocyte plasma membrane and astrocyte cytoplasm. Serum samples from 26.3% BP and 28.6% dementia patients and 7.1% elderly controls recognized the 180-kDa and/or 230-kDa proteins in both keratinocytes and astrocytes by immunoblot experiments, confirming molecular mimicry between skin and CNS proteins. Thus, a pathogenic mechanism for the association dementia-BP is proposed. Neurodegeneration and neuroinflammation - represented by dementia - may trigger autoantibody production against the neural 180-kDa and 230-kDa isoforms, recognized as non-self-proteins in the CNS. The consequent cross-reactivity of these isoforms with skin BP180 and BP230 proteins could trigger BP onset following dementia diagnosis. (AU) | |
| FAPESP's process: | 16/09011-3 - Association of bullous pemphigoid with dementia: investigation of antigenic molecular mimicry between hemidesmose skin peptides and neuronal peptides |
| Grantee: | Tamíris Amanda Júlio |
| Support Opportunities: | Scholarships in Brazil - Doctorate |