Association of bullous pemphigoid with dementia: investigation of antigenic molecular mimicry between hemidesmose skin peptides and neuronal peptides

• Grant number: 16/09011-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2016
• End date: September 30, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ana Maria Ferreira Roselino
• Grantee: Tamíris Amanda Júlio
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Introduction: Bullous pemphigoid (BP) is an autoimmune skin disease that leads to the production of autoantibodies against BP180 and BP230 proteins. The recognition of BP peptides by circulating autoantibodies leads to subepidermal blister, which pathogenesis is focused on neutrophil chemotaxis by mast cell degranulation. Our group has shown that the BP is associated with neurological diseases (26%), being distributed in 16% with dementia, 6% with stroke and 4% with epilepsy. Research Hypothesis: As BP180/230 peptides are also expressed in the central nervous system, the production of anti-BP180/230 contribute to the clinical co-expression of BP and dementia. Objective: To investigate the molecular mimicry of hemidesmossomal peptides expressed in human skin and in keratinocyte cells (KC) with neuronal peptides by using three neuronal cells lines in the relation of BP with dementia. Methodology: Protein extracts of KC and neuronal cells will be used for antibody production in rabbits that will be validated by contraimmunoelectroforesis and flow cytometry. Indirect immunofluorescence will be used to determine whether serum from BP patients and from dementia patients compared to healthy erderly controls and to anti-BP180/230 commercial antibodies recognize proteins of the human skin and 4 cell lines. Human skin protein extract and cell lines protein extracts will be used in immunoblotting. The protein fractions recognized by the serum from patients and immunized rabbits will be sequenced and analyzed. Expected results: It is expected to contribute to the hypothesis of antigenic mimicry between the skin and neural peptides, which can be synthesized for future studies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VERNAL, SEBASTIAN; JULIO, TAMIRIS; CRUZ, FERNANDA; TURATTI, ALINE; ISHII, NORITO; HASHIMOTO, TAKASHI; ROSELINO, ANA MARIA. Bullous Pemphigoid Associated with Ischemic Cerebrovascular Accident and Dementia: Exclusive Blistering Lesions on the Upper Hemiparetic Limb. ACTA DERMATOVENEROLOGICA CROATICA, v. 26, n. 2, p. 179-182, 2018. (16/09011-3, 10/51729-2)

JULIO, TAMIRIS A.; VERNAL, SEBASTIAN; MASSARO, JULIANA D.; SILVA, MATHEUS C.; DONADI, EDUARDO A.; MORIGUTI, JULIO C.; ROSELINO, ANA M.. Biological predictors shared by dementia and bullous pemphigoid patients point out a cross-antigenicity between BP180/BP230 brain and skin isoforms. IMMUNOLOGIC RESEARCH, v. 66, n. 5, p. 567-576, OCT 2018. (10/51729-2, 16/09011-3)

BRANDAO MIGUEL, MARCELA CALIXTO; JULIO, TAMIRIS AMANDA; VERNAL, SEBASTIAN; DE PAULA, NATALIA APARECIDA; LIEBER, ANDRE; ROSELINO, ANA MARIA. Autoantibodies against desmoglein 2 are not pathogenic in pemphigus. ANAIS BRASILEIROS DE DERMATOLOGIA, v. 97, n. 2, p. 12-pg., 2022-03-11. (16/09011-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

JÚLIO, Tamíris Amanda. Molecular mimicry between BP180/BP230 hemidesmosomal proteins and neural isoforms in the association of bullous pemphigoid with dementia. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.