The role of IgG FC N-glycosylation on the pathogenesis of visceral leishmaniasis: insights into new strategies of therapy

• Grant number: 16/18527-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): January 01, 2017
• Effective date (End): November 30, 2020
• Field of knowledge: Biological Sciences - Immunology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Isabel Kinney Ferreira de Miranda Santos
• Grantee: Gabriane Nascimento Porcino
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 19/15738-1 - I.Study of Total Serum N-glycan signatures in infections with Leishmania infantum in a Brazilian population, BE.EP.PD

Abstract

Visceral leishmaniasis (VL) may be fatal if not treated and, although hypergammaglobulinemia is a hallmark of VL, the contribution of antibodies in progression of disease remains unknown. Effector and regulatory functions of antibodies rely on their interactions with type I and II Fc receptors and these interactions are tuned by the patterns of antibody Fc N-glycosylation. We recently showed that, in comparison to healthy individuals, the overall IgG Fc N-glycan profiles are profoundly altered in VL patients and, together with serum regulators of immune responses (cytokines and C-reactive protein), we demonstrated the ability of IgG Fc glyco features to predict disease severity in VL patients. Importantly, we showed that Fc N-glycosylation profiles change after treatment of VL. We will begin to uncover the potential role of IgG Fc glyco features in the pathogenesis of VL and the mechanisms that participate in those alterations with the following studies: (i) we will evaluate global gene expression profiles of B cells isolated from patients stratified into categories of disease severity, and associate them with titers and profiles of Fc Nglycosylation of IgG specific for leishmania antigens; (ii) based on the knowledge acquired by our study on VL patients, we will test the viability and efficacy of new strategies of therapy in an experimental hamster model of progressive VL. We will evaluate the effects of treatment of hamsters chronically infected with L. infantum with intravenous immunoglobulin preparations enriched with sialic acid, and in vivo enzymatic deglycosylation of IgG Fc. Thus, we expect to obtain insights into the mechanisms by which IgG Fc glyco features influence progression and severity of VL and to innovate the treatment of the disease. (AU)

Scientific publications

(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)

PORCINO, GABRIANE NASCIMENTO; SOUSA CARVALHO, KATIA SILENE; BRAZ, DEBORA CAVALCANTE; SILVA, VLADIMIR COSTA; NERY COSTA, CARLOS HENRIQUE; FERREIRA DE MIRANDA SANTOS, ISABEL KINNEY. Evaluation of methods for detection of asymptomatic individuals infected with Leishmania infantum in the state of Piaui, Brazil. PLoS Neglected Tropical Diseases, v. 13, n. 7, JUL 2019. (15/07820-9, 16/18527-3)

TAKAMIYA, NAYORE TAMIE; ROGERIO, LUANA APARECIDA; TORRES, CAROLINE; LEONEL, JOAO AUGUSTO FRANCO; VIOTI, GEOVANNA; OLIVEIRA, TRICIA MARIA FERREIRA DE SOUSA; VALERIANO, KAROLINE CAMILA; PORCINO, GABRIANE NASCIMENTO; SANTOS, ISABEL KINNEY FERREIRA DE MIRANDA; COSTA, CARLOS H. N.; et al. Parasite Detection in Visceral Leishmaniasis Samples by Dye-Based qPCR Using New Gene Targets of Leishmania infantum and Crithidia. TROPICAL MEDICINE AND INFECTIOUS DISEASE, v. 8, n. 8, p. 25-pg., 2023-08-01. (21/12464-8, 16/18527-3, 18/26799-9, 19/19789-0, 16/20258-0, 21/10358-6, 20/15771-6, 20/14011-8, 17/16328-6)

PORCINO, GABRIANE NASCIMENTO; BLADERGROEN, MARCO RENE; DOTZ, VIKTORIA; NICOLARDI, SIMONE; MEMARIAN, ELHAM; GARDINASSI, LUIZ GUSTAVO; COSTA, CARLOS HENRIQUE NERY; ALMEIDA, ROQUE PACHECO DE; SANTOS, ISABEL KINNEY FERREIRA DE MIRANDA; WUHRER, MANFRED. Total serum N-glycans mark visceral leishmaniasis in human infections with Leishmania infantum. ISCIENCE, v. 26, n. 7, p. 24-pg., 2023-07-21. (19/19789-0, 16/18527-3, 15/07820-9)