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Mémoire de Maîtrise
DOI
https://doi.org/10.11606/D.42.2018.tde-03052018-160217
Document
Auteur
Nom complet
Ana Catarina Lunz Macedo
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2018
Directeur
Jury
Isaac, Lourdes (Président)
Andrade, Luis Eduardo Coelho
Câmara, Niels Olsen Saraiva
Pastorino, Antonio Carlos
Titre en portugais
Efeito da curcumina na secreção de fator H mutante em paciente deficiente desta proteína reguladora do sistema complemento.
Mots-clés en portugais
Chaperona
Curcumina
Fator H
Imunodeficiência
Tratamento experimental
Resumé en portugais
Nosso grupo estudou paciente com antecedente de infecções graves e deficiência homozigota Fator H (mutação CG453T→CA453T). Esta mutação leva a troca de códon Arg127His na molécula de Fator H (FH) resultando em acúmulo deste no retículo endoplasmático. Quando tratada a cultura de fibroblastos do paciente com curcumina in vitro, estes apresentaram aumento de secreção do FH, que mesmo mutado, apresentava função reguladora preservada. Neste protocolo, foi utilizado Theracurmin® (curcumina nanopartículada) para tratar a deficiência de FH deste paciente. Em avaliação prévia ao tratamento, foi diagnosticado lúpus com grau de atividade SLEDAI 4/105. No tratamento experimental, foram avaliados nível plasmático de curcumina e tetrahidrocurcumina. O paciente não apresentou sintomas adversos. Foi possível identificar que os níveis de curcumina e seus metabólitos se relacionaram a discreto aumento de FH detectado por Western Blot, porém sem normalização do FH e C3. O grau de atividade do lúpus se manteve estável ao longo de todo o tratamento.
Titre en anglais
Effect of curcumin on mutant H-factor secretion in a deficient patient of this complement regulatory system protein.
Mots-clés en anglais
Chaperone
Curcumin
Experimental treatment
Factor H
Immunodeficiency
Resumé en anglais
Our group investigated a patient with a past of severe infections and homozygous deficiency Factor H (mutation CG453T → CA453T). This mutation leads to Arg127His codon exchange in the Factor H (FH) molecule resulting in accumulation of this protein in the endoplasmic reticulum. Once the culture of fibroblasts of the patient was treated with curcumin in vitro, they presented increased secretion of FH, which had his regulatory function. In this protocol, Theracurmin® (nanoparticle curcumin) was used to treat the FH deficiency of this patient. In pre-treatment evaluation, the pacient was diagnosed lupus with SLEDAI grade of activity 4/105. In the experimental treatment, plasma levels of curcumin and tetrahydrocurcumin were evaluated. The patient hasn't had adverse symptoms. It was possible to identify that the levels of curcumin and its metabolites were related to the discrete increase of FH detected by Western Blot, but without normalization of FH and C3. The degree of lupus activity remained stable throughout the treatment.
 
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Date de Libération
2020-10-07
Date de Publication
2018-10-08
 
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