Chromosomal segments may explain the antibody response cooperation for canine leishmaniasis pathogenesis

• Published in: Veterinary parasitology Vol. 288; p. 109276
• Main Authors: Batista, Luís F.S., Torrecilha, Rafaela B.P., Silva, Rafaela B., Utsunomiya, Yuri T., Silva, Thaís B.F., Tomokane, Thaíse Y., Pacheco, Acácio D., Bosco, Anelise M., Paulan, Silvana C., Rossi, Claudio N., Costa, Gustavo N.O., Marcondes, Mary, Ciarlini, Paulo C., Nunes, Cáris M., Matta, Vânia L.R., Laurenti, Márcia D.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2020
• Subjects: Antiboby response; Canine leishmaniasis; GWAS; Oxidative stress; Renal-hepatic changes; Oxidative stress; Canine leishmaniasis; Antiboby response; GWAS; Renal-hepatic changes
• ISSN: 0304-4017; 1873-2550
• DOI: 10.1016/j.vetpar.2020.109276

[Display omitted] •IgG, IgA, IgE higher in severely sick whereas IgM higher in exposed dogs.•IgG and IgA responses were positively correlated with parasite load.•Renal and hepatic biochemical changes correlated with IgM, IgG, IgA.•IgM, IgG and IgA responses were correlated with oxidative stress.•Ig genetics involves ROS/Fe availability, phagolysosome rupture, T cell fate. Visceral leishmaniasis (VL) is marked by hyperactivation of a humoral response secreting high quantity of immunoglobulins (Igs) that are inaccessible to intracellular parasites. Here we investigated the contributions of the antibody response to the canine leishmaniasis pathogenesis. Using correlation and genome-wide association analysis, we investigated the relationship of anti-Leishmania infantum immunoglobulin classes levels with parasite burden, clinical response, renal/hepatic biochemical, and oxidative stress markers in dogs from endemic areas of VL. Immunoglobulin G (IgG) and IgA were positively correlated with parasite burden on lymph node and blood. Increased IgG, IgA and IgE levels were associated with severe canine leishmaniasis (CanL) whereas IgM was elevated in uninfected exposed dogs. Correlations of IgM, IgG and IgA with creatinine, urea, AST and ALT levels in the serum were suggested an involvement of those Igs with renal and hepatic changes. The correlogram of oxidative radicals and antioxidants revealed a likely relationship of IgM, IgG and IgA with oxidative stress and lipid peroxidation in the blood, suggested as mechanisms mediating tissue damage and CanL worsening. The gene mapping on chromosomal segments associated with the quantitative variation of immunoglobulin classes identified genetic signatures involved with reactive oxygen species generation, phagolysosome maturation and rupture, free iron availability, Th1/Th2 differenciation and, immunoglobulin clearance. The findings demonstrated the roles of the antibody response as resistance or susceptibility markers and mediators of CanL pathogenesis. In addition we pinpointed candidate genes as potential targets for the therapy against the damage caused by exacerbated antibody response and parasitism in VL.