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

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)

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