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Serum antibodies blocked by glycan antigens in canine visceral leishmaniasis serology are mostly IgA immune complexes

Published online by Cambridge University Press:  05 July 2021

Camila Aparecida de Carvalho*
Affiliation:
Laboratório de Protozoologia – Instituto de Medicina Tropical da Faculdade de Medicina da Universidade de São Paulo, Av. Doutor Enéas de Carvalho Aguiar, 470, CEP 05403-000, São Paulo, SP, Brazil Departamento de Patologia – Faculdade de Medicina da Universidade de São Paulo, Av. Doutor Enéas de Carvalho Aguiar, 470, CEP 05403-000, São Paulo – SP, Brazil
Roberto Mitsuyoshi Hiramoto
Affiliation:
Laboratório de Parasitoses Sistêmicas – Instituto Adolfo Lutz, Av. Dr Arnaldo, 355, CEP 01246-000, São Paulo – SP, Brazil
Luciana Regina Meireles
Affiliation:
Laboratório de Protozoologia – Instituto de Medicina Tropical da Faculdade de Medicina da Universidade de São Paulo, Av. Doutor Enéas de Carvalho Aguiar, 470, CEP 05403-000, São Paulo, SP, Brazil
Heitor Franco de Andrade Júnior
Affiliation:
Laboratório de Protozoologia – Instituto de Medicina Tropical da Faculdade de Medicina da Universidade de São Paulo, Av. Doutor Enéas de Carvalho Aguiar, 470, CEP 05403-000, São Paulo, SP, Brazil Departamento de Patologia – Faculdade de Medicina da Universidade de São Paulo, Av. Doutor Enéas de Carvalho Aguiar, 470, CEP 05403-000, São Paulo – SP, Brazil
*
Author for correspondence: Camila Aparecida de Carvalho, E-mail: [email protected], [email protected]

Abstract

Immune complexes (ICs) are found in canine visceral leishmaniasis (CVL) and interfere with the serum detection of antibodies. Dissociation of these monovalent complexes by dissociative enzyme-linked immunosorbent assay (ELISA) removes false-negative results and allows some characterization of antibodies and antigens. We studied the serology of dogs with suspected CVL in an endemic area, testing two Leishmania (Leishmania) [L. (L.)] <full form>infantum antigens. We analysed the presence of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) antibodies specific to promastigote soluble extract (PSE) and low-molecular weight glycans (glycan–bovine serum albumin (BSA) complex – GBC) by conventional and dissociative ELISA. Our results showed a significant fraction of IgA ICs (46.5% for PSE and 47.6% for GBC), followed by IgG ICs (10% for PSE and 23.5% for GBC). IgM ICs were more frequent for PSE (22.7%). Hypergammaglobulinaemia in CVL would be related to the presence of IgA and IgG ICs, resulting in deficient elimination of these antibodies. Our data confirmed the presence of ICs that can generate false-negative results in conventional serology. The production of IgA antibodies and the high frequency of blockade by glycan antigens suggest the active participation of this immunoglobulin and its ICs in the immunopathology of CVL, indicating a new path for further research.

Type
Research Article
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Aibara, N and Ohyama, K (2020) Revisiting immune complexes: key to understanding immune-related diseases. Advances in Clinical Chemistry 96, 117.CrossRefGoogle ScholarPubMed
Aparecida de Carvalho, C, Fidelis Ferrão, T, Mitsuyoshi Hiramoto, R, Kelsei Partata, A and de Andrade Júnior, HF (2019) Indirect evidence of circulating parasite hapten immune complexes in visceral leishmaniasis. The Journal of Applied Laboratory Medicine 4, 404409.CrossRefGoogle ScholarPubMed
Baneth, G, Koutinas, AF, Solano-Gallego, L, Bourdeau, P and Ferrer, L (2008) Canine leishmaniosis – new concepts and insights on an expanding zoonosis: part one. Trends in Parasitology 24, 324330.CrossRefGoogle Scholar
Batista, L, Torrecilha, R, Silva, RB, Utsunomiya, YT, Silva, T, Tomokane, TY, Pacheco, AD, Bosco, AM, Paulan, SC, Rossi, CN, Costa, G, Marcondes, M, Ciarlini, PC, Nunes, CM, Matta, V and Laurenti, MD (2020) Chromosomal segments may explain the antibody response cooperation for canine leishmaniasis pathogenesis. Veterinary Parasitology 288, 109276.CrossRefGoogle ScholarPubMed
Brodskyn, CI and Kamhawi, S (2018) Biomarkers for zoonotic visceral leishmaniasis in Latin America. Frontiers in Cellular and Infection Microbiology 8, 245.CrossRefGoogle ScholarPubMed
Cabezas, Y, Legentil, L, Robert-Gangneux, F, Daligault, F, Belaz, S, Nugier-Chauvin, C, Tranchimand, S, Tellier, C, Gangneux, JP and Ferrières, V (2015) Leishmania cell wall as a potent target for antiparasitic drugs. A focus on the glycoconjugates. Organic & Biomolecular Chemistry 13, 83938404.CrossRefGoogle ScholarPubMed
Cantos-Barreda, A, Escribano, D, Egui, A, Thomas, MC, López, MC, Tecles, F, Bernal, LJ, Cerón, JJ and Martínez-Subiela, S (2019) One-year follow-up of anti-Leishmania antibody concentrations in serum and saliva from experimentally infected dogs. International Journal for Parasitology 49, 893900.CrossRefGoogle ScholarPubMed
de Carvalho, CA, Partata, AK, Hiramoto, RM, Borborema, SE, Meireles, LR, Nascimento, ND and de Andrade, HF Jr (2013) A simple immune complex dissociation ELISA for leishmaniasis: standardization of the assay in experimental models and preliminary results in canine and human samples. Acta Tropica 125, 128136.CrossRefGoogle ScholarPubMed
de Carvalho, CA, Ferrão, TF, de Freitas, F and de Andrade, HF Jr (2019) High levels of serum glycans monovalent IgG immune complexes detected by dissociative ELISA in experimental visceral leishmaniasis. Immunology 158, 314321.CrossRefGoogle ScholarPubMed
de Carvalho, CA, Ferrão, TF, Cavalcante, FS, de Freitas, F, Meireles, LR and de Andrade Júnior, HF (2020) Early high avidity specific IgG production in experimental hamster visceral leishmaniasis. Parasitology Research 119, 38813885.CrossRefGoogle ScholarPubMed
de Freitas, JC, Lopes-Neto, BE, de Abreu, CR, Coura-Vital, W, Braga, SL, Reis, AB and Nunes-Pinheiro, DC (2012) Profile of anti-Leishmania antibodies related to clinical picture in canine visceral leishmaniasis. Research in Veterinary Science 93, 705709.CrossRefGoogle ScholarPubMed
Diniz, SA, Silva, FL, Carvalho Neta, AC, Bueno, R, Guerra, RM, Abreu-Silva, AL and Santos, RL (2008) Animal reservoirs for visceral leishmaniasis in densely populated urban areas. Journal of Infection in Developing Countries 2, 2433.Google ScholarPubMed
Di Pietro, S, Crinò, C, Falcone, A, Crupi, R, Francaviglia, F, Vitale, F and Giudice, E (2020) Parasitemia and its daily variation in canine leishmaniasis. Parasitology Research 119, 35413548.CrossRefGoogle ScholarPubMed
Freitas, JC, Nunes-Pinheiro, DC, Lopes Neto, BE, Santos, GJ, Abreu, CR, Braga, RR, Campos, R and Oliveira, LF (2012) Clinical and laboratory alterations in dogs naturally infected by Leishmania chagasi. Revista da Sociedade Brasileira de Medicina Tropical 45, 2429.CrossRefGoogle ScholarPubMed
Guilliams, M, Bruhns, P, Saeys, Y, Hammad, H and Lambrecht, BN (2014) The function of Fcγ receptors in dendritic cells and macrophages. Nature Reviews. Immunology 14, 94108.CrossRefGoogle ScholarPubMed
Hosein, S, Blake, DP and Solano-Gallego, L (2017) Insights on adaptive and innate immunity in canine leishmaniosis. Parasitology 144, 95115. https://doi.org/10.1017/S003118201600055X.CrossRefGoogle ScholarPubMed
Jaiswal, P, Datta, S, Sardar, B, Chaudhuri, SJ, Maji, D, Ghosh, M, Saha, B and Mukhopadhyay, S (2018) Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: a study from endemic districts of West Bengal, India. PLoS One 13, e0192302.CrossRefGoogle ScholarPubMed
Macedo, AC and Isaac, L (2016) Systemic lupus erythematosus and deficiencies of early components of the complement classical pathway. Frontiers in Immunology 7, 55.CrossRefGoogle ScholarPubMed
Maia, C and Campino, L (2018) Biomarkers associated with Leishmania infantum exposure, infection, and disease in dogs. Frontiers in Cellular and Infection Microbiology 8, 302.CrossRefGoogle ScholarPubMed
Marcondes, M and Day, MJ (2019) Current status and management of canine leishmaniasis in Latin America. Research in Veterinary Science 123, 261272.CrossRefGoogle ScholarPubMed
Martinez-Subiela, S, Strauss-Ayali, D, Cerón, JJ and Baneth, G (2011) Acute phase protein response in experimental canine leishmaniasis. Veterinary Parasitology 180, 197202.CrossRefGoogle ScholarPubMed
Muthana, SM, Xia, L, Campbell, CT, Zhang, Y and Gildersleeve, JC (2015) Competition between serum IgG, IgM, and IgA anti-glycan antibodies. PLoS One 10, e0119298.CrossRefGoogle ScholarPubMed
Olías-Molero, AI, Moreno, I, Corral, MJ, Jiménez-Antón, MD, Day, MJ, Domínguez, M and Alunda, JM (2020) Infection of dogs by Leishmania infantum elicits a general response of IgG subclasses. Scientific Reports 10, 18826.CrossRefGoogle ScholarPubMed
Parody, N, Cacheiro-Llaguno, C, Osuna, C, Renshaw-Calderón, A, Alonso, C and Carnés, J (2019) Circulating immune complexes levels correlate with the progression of canine leishmaniosis in naturally infected dogs. Veterinary Parasitology 274, 108921.CrossRefGoogle ScholarPubMed
Pereira, IE, Silva, KP, Menegati, LM, Pinheiro, AC, Assunção, E, de Lourdes, P, Araújo, M, Abass, E, Duthie, MS, Steinhoff, U and Teixeira, HC (2020) Performance of recombinant proteins in diagnosis and differentiation of canine visceral leishmaniasis infected and vaccinated dogs. European journal of Microbiology & Immunology 10, 165171.CrossRefGoogle ScholarPubMed
Pinelli, E, van der Kaaij, SY, Slappendel, R, Fragio, C, Ruitenberg, EJ, Bernadina, W and Rutten, VP (1999) Detection of canine cytokine gene expression by reverse transcription-polymerase chain reaction. Veterinary Immunology and Immunopathology 69, 121126.CrossRefGoogle ScholarPubMed
Reis, AB, Teixeira-Carvalho, A, Vale, AM, Marques, MJ, Giunchetti, RC, Mayrink, W, Guerra, LL, Andrade, RA, Corrêa-Oliveira, R and Martins-Filho, OA (2006) Isotype patterns of immunoglobulins: hallmarks for clinical status and tissue parasite density in Brazilian dogs naturally infected by Leishmania (Leishmania) chagasi. Veterinary Immunology and Immunopathology 112, 102116.CrossRefGoogle ScholarPubMed
Rodríguez-Cortés, A, Fernández-Bellón, H, Ramis, A, Ferrer, L, Alberola, J and Solano-Gallego, L (2007) Leishmania-specific isotype levels and their relationship with specific cell-mediated immunity parameters in canine leishmaniasis. Veterinary Immunology and Immunopathology 116, 190198.CrossRefGoogle ScholarPubMed
Sampaio, JR, Soares, RP, Barral, TD, Passos, GP, Fonseca, MS, Meyer, R, Barrouin-Melo, SM and Portela, RW (2021) Leishmania infantum-derived glycoinositolphospholipids in the immunodiagnosis of subclinically infected dogs. Frontiers in Veterinary Science 8, 581148.CrossRefGoogle ScholarPubMed
Toepp, AJ and Petersen, CA (2020) The balancing act: immunology of leishmaniosis. Research in Veterinary Science 130, 1925.CrossRefGoogle ScholarPubMed
Valente, M, Castillo-Acosta, VM, Vidal, AE and González-Pacanowska, D (2019) Overview of the role of kinetoplastid surface carbohydrates in infection and host cell invasion: prospects for therapeutic intervention. Parasitology 146, 17431754.CrossRefGoogle ScholarPubMed
World Health Organization (2019) Leishmaniasis. Retrieved from World Health Organization website: http://www.who.int/mediacentre/factsheets/fs375/en/ (accessed 26 April 2021).Google Scholar
Yeo, SC, Cheung, CK and Barratt, J (2018) New insights into the pathogenesis of IgA nephropathy. Pediatric Nephrology 33, 763777.CrossRefGoogle ScholarPubMed