Effect of induction of tolerance with immunogenic peptides of collagen type V on pulmonary fibrosis associated with experimental systemic sclerosis

• Grant number: 21/13220-5
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2022
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Ana Paula Pereira Velosa
• Grantee: Ana Paula Pereira Velosa
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Claudia Goldenstein Schainberg ; Maria Notomi Sato ; Pedro Leme Silva ; Sergio Catanozi ; Solange Carrasco ; Vera Luiza Capelozzi ; Walcy Paganelli Rosolia Teodoro
• Associated scholarship(s): 23/03071-8 - STUDY OF TOLERANCE MECHANISMS INDUCED BY ORAL ADMINISTRATION OF IMMUNOGENIC COLLAGEN V PEPTIDES IN A MODEL OF SYSTEMIC SCLEROSIS., BP.TT

Abstract

Type V collagen (Col V) has immunogenic and antigenic features and potential to become an autoantigen in various pathologies, when exposed to the immune system. Studies have shown an increase in the frequency of anti-Col V antibodies in the serum of patients in the early stages of systemic sclerosis (SSc), a chronic disease characterized by fibrosis of the skin and internal organs, such as the lung. Also, in a recent publication, resulting from the project support by FAPESP, we showed the prevalence of autoimmunity for the ±1(V) chain in the early stages of SSc and significant immunological reactivity for the Col5A1(1,049) and Col5A1(1,439) peptides of the ±1(V) chain in the serum of these patients, suggesting that these ±1(V) chain peptides may be related to autoimmunity to Col V in SSc. In the present study, using the ES model induced in C57BL/6 mice, by immunization with Col V, and considering the tolerogenic environment of the mucosa, we propose to evaluate the induction of tolerance in the ES model, through the oral route, addressing two aspects: 1) prophylactic tolerance, with Col5A1(1,049) and Col5A1(1,439) peptides and ±1(V) chain, two weeks before the induction of the ES model, and 2) tolerance as immunotherapy, with the most effective peptide in induction of tolerance (tolerogenic), initiated 75 days after the establishment of the ES model. This study can be of great value for the establishment of future therapies, based on biotechnological methodologies and production of biopharmaceuticals with tolerogenic portions of Col V, which could be an adjunct to the treatment of patients with SSc, with minimal side effects. (AU)

Scientific publications

(4)

(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)

DE MORAIS, JYMENEZ; VELOSA, ANA PAULA P.; ANDRADE, PRISCILA C.; FREDIANI, DENISE; CARRASCO, SOLANGE; QUEIROZ, ZELITA A. DE JESUS; MARTIN, PATRICIA; SAITO, RENATA F.; ELIAS, VITORIA; GOLDENSTEIN-SCHAINBERG, CLAUDIA; et al. Collagen V alpha 1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 20, p. 14-pg., 2022-10-01. (18/20403-6, 18/00415-0, 21/13220-5)

RAMOS DA SILVEIRA, LIZANDRE KEREN; VELOSA, ANA PAULA P.; CATANOZI, SERGIO; PEREIRA, MARCO AURELIO A.; DOS SANTOS FILHO, ANTONIO; MARQUES, FABIO LUIZ N.; DE PAULA FARIA, DANIELE; REAL, CAROLINE CRISTIANO; FERNEZLIAN, SANDRA DE M.; YANKE, AMANDA FLORES; et al. Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis. PLoS One, v. 19, n. 10, p. 15-pg., 2024-10-08. (19/24178-0, 23/02755-0, 18/20403-6, 21/13220-5)

VELOSA, A. P.; DE MATOS LOBO, T.; JESUS QUEIROZ, Z. A.; DOS SANTOS FILHO, A.; RODRIGUES DE SOUZA, V. D.; ALVES ALMEIDA, J.; DE MORAIS FERNEZLIAN, S.; MACHADO BALDAVIRA, C.; KEREN RAMOS DA SILVEIRA, L.; CATANOZI, S.; et al. Collagen V α1 chain oral tolerance attenuates the lung fibrosis and vascular reactivity in systemic sclerosis model. Virchows Archiv, v. 485, p. 1-pg., 2024-09-01. (21/13220-5)

ROBERTONI, FABIOLA SANTOS ZAMBON; VELOSA, ANA PAULA PEREIRA; OLIVEIRA, LUANA DE MENDONCA; DE ALMEIDA, FRANCINE MARIA; DA SILVEIRA, LIZANDRE KEREN RAMOS; QUEIROZ, ZELITA APARECIDA DE JESUS; LOBO, THAYS DE MATOS; CONTINI, VITORIA ELIAS; BALDAVIRA, CAMILA MACHADO; CARRASCO, SOLANGE; et al. Type V collagen-induced nasal tolerance prevents lung damage in an experimental model: new evidence of autoimmunity to collagen V in COPD. FRONTIERS IN IMMUNOLOGY, v. 15, p. 17-pg., 2024-09-05. (21/13220-5)