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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2018.tde-03052018-160217
Document
Author
Full name
Ana Catarina Lunz Macedo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Isaac, Lourdes (President)
Andrade, Luis Eduardo Coelho
Câmara, Niels Olsen Saraiva
Pastorino, Antonio Carlos
Title in Portuguese
Efeito da curcumina na secreção de fator H mutante em paciente deficiente desta proteína reguladora do sistema complemento.
Keywords in Portuguese
Chaperona
Curcumina
Fator H
Imunodeficiência
Tratamento experimental
Abstract in Portuguese
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.
Title in English
Effect of curcumin on mutant H-factor secretion in a deficient patient of this complement regulatory system protein.
Keywords in English
Chaperone
Curcumin
Experimental treatment
Factor H
Immunodeficiency
Abstract in English
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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Release Date
2020-10-07
Publishing Date
2018-10-08
 
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