Estudo dos mecanismos associados à responsividade a terapia antirreumática

• Ano de defesa: 2021
• Autor(a) principal: RODRIGUES, João Francisco Silva
• Orientador(a): FERNANDES, Elizabeth Soares
• Banca de defesa: FERNANDES, Elizabeth Soares , MONTEIRO NETO, Valério , GUERRA, Rosane Nassar Meireles , ANDRÉ, Eunice , LIMA NETO, Lídio Gonçalves de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Maranhão
• Programa de Pós-Graduação: PROGRAMA DE PÓS-GRADUAÇÃO EM REDE - REDE DE BIODIVERSIDADE E BIOTECNOLOGIA DA AMAZÔNIA LEGAL/CCBS
• Departamento: DEPARTAMENTO DE BIOLOGIA/CCBS
• País: Brasil
• Palavras-chave em Português: Artrite; FTIR; Não respondedores; Leflunomida; Adalimumabe
• Palavras-chave em Inglês: Arthritis; FTIR; Non-responders; Leflunomide; Adalimumab
• Área do conhecimento CNPq: Ciências da Saúde
• Link de acesso: https://tedebc.ufma.br/jspui/handle/tede/tede/3404

Rheumatoid arthritis (RA) affects thousands of people worldwide, about 1% of the world's adult population. It is defined as inflammation of one or more joints, with the presence of pain, swelling, erythema and increased temperature in the affected region. Current therapy consists of using non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying agents (DMARDS) and biological agents such as anti-TNF. Still, due to mechanisms that have not yet been fully elucidated, a portion of the patients does not respond to any existing therapeutic line, remaining at the same time to live with the progressive symptoms of this pathology. Initially, we conducted a pilot study to investigate the potential use of flow cytometry and infrared spectroscopy with attenuated total reflection Fourier transform (ATR-FTIR) as measures to identify responders and non-responders to leflunomide, a disease-modifying drug used in treatment of RA patients. By evaluating the number of CD62L + polymorphonuclear cells in peripheral blood and the vibrational ATR-FTIR modes in plasma, it was possible to discriminate responders to LFN three months after the start of therapy. The results indicate that both flow cytometry and ATR-FTIR can potentially be used as additional measures to monitor an early treatment response to LFN in RA patients. In the second manuscript, we investigated RA markers in peripheral blood, using a model of CFA-induced joint inflammation in CD1 mice, we were able to identify responders and non-responders to Adalimumab (Ada) (100 μg / mouse / week; 3 weeks). Ada responders exhibited a reduced population of CD8+ CD69+ cells, as well as decreased expression of MHC II-associated genes (H2-Ea and H2-Eb1) in their peripheral blood leukocytes. These results demonstrate that CFA-induced arthritis in CD1 mice can be used as a useful non-clinical model of joint inflammation to investigate anti-TNF drugs, as well as the mechanisms underlying the chances of success and failure of such therapies in RA.