title: Anti-erythrocyte antibodies may contribute to anaemia in Plasmodium vivax malaria by decreasing red blood cell deformability and increasing erythrophagocytosis.
abstract: Plasmodium vivax accounts for the majority of human malaria infections outside Africa and is being increasingly associated in fatal outcomes with anaemia as one of the major complications. One of the causes of malarial anaemia is the augmented removal of circulating non-infected red blood cells (nRBCs), an issue not yet fully understood. High levels of auto-antibodies against RBCs have been associated with severe anaemia and reduced survival of nRBCs in patients with falciparum malaria. Since there are no substantial data about the role of those antibodies in vivax malaria, this study was designed to determine whether or not auto-antibodies against erythrocytes are involved in nRBC clearance. Moreover, the possible immune mechanisms elicited by them that may be associated to induce anaemia in P. vivax infection was investigated.
  
  
  
  Concentrations of total IgG were determined by sandwich ELISA in sera from clinically well-defined groups of P. vivax-infected patients with or without anaemia and in healthy controls never exposed to malaria, whereas the levels of specific IgG to nRBCs were determined by cell-ELISA. Erythrophagocytosis assay was used to investigate the ability of IgGs purified from each studied pooled sera in enhancing nRBC in vitro clearance by THP-1 macrophages. Defocusing microscopy was employed to measure the biomechanical modifications of individual nRBCs opsonized by IgGs purified from each group.
  
  
  
  Anaemic patients had higher levels of total and specific anti-RBC antibodies in comparison to the non-anaemic ones. Opsonization with purified IgG from anaemic patients significantly enhanced RBCs in vitro phagocytosis by THP-1 macrophages. Auto-antibodies purified from anaemic patients decreased the nRBC dynamic membrane fluctuations suggesting a possible participation of such antibodies in the perturbation of erythrocyte flexibility and morphology integrity maintenance.
  
  
  
  These findings revealed that vivax-infected patients with anaemia have increased levels of IgG auto-antibodies against nRBCs and that their deposition on the surface of non-infected erythrocytes decreases their deformability, which, in turn, may enhance nRBC clearance by phagocytes, contributing to the anaemic outcome. These data provide insights into the immune mechanisms associated with vivax malaria anaemia and may be important to the development of new therapy and vaccine strategies.
authors.affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Luiza Carvalho
authors.initials: LC
authors.lastname: Mourão
authors.affiliation: Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Paula Magda da Silva
authors.initials: PM
authors.lastname: Roma
authors.affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Jamila da Silva
authors.initials: Jda S
authors.lastname: Sultane Aboobacar
authors.affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Camila Maia Pantuzzo
authors.initials: CM
authors.lastname: Medeiros
authors.affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Zélia Barbosa
authors.initials: ZB
authors.lastname: de Almeida
authors.affiliation: Faculdade de Ciências Médicas, Universidade Federal do Mato Grosso, Cuiabá, MT, Brazil.
authors.forename: Cor Jesus Fernandes
authors.initials: CJ
authors.lastname: Fontes
authors.affiliation: Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Ubirajara
authors.initials: U
authors.lastname: Agero
authors.affiliation: Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Oscar Nassif
authors.initials: ON
authors.lastname: de Mesquita
authors.affiliation: Embrapa Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil.
authors.forename: Marcelo Porto
authors.initials: MP
authors.lastname: Bemquerer
authors.affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. embraga@icb.ufmg.br.
authors.forename: Érika Martins
authors.initials: ÉM
authors.lastname: Braga
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000209:etiology*; D001323:Autoantibodies / Q000097:blood*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016780:Malaria, Vivax / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009895:Opsonin Proteins / Q000097:blood*; D010587:Phagocytosis; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D009895:Opsonin Proteins
keywords: Anaemia; Auto-antibodies; Defocusing microscopy; Erythrophagocytosis; Non-infected RBC; Plasmodium vivax