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.

内脏利什曼病（VL）的特征是体液反应过度活化，分泌大量细胞内寄生虫无法获得的免疫球蛋白（Ig）。在这里，我们调查了抗体反应对犬利什曼病的发病机理的贡献。使用相关性和全基因组关联分析，我们调查了抗婴儿利什曼原虫的关系VL流行地区犬的免疫球蛋白类别水平与寄生虫负担，临床反应，肾脏/肝脏生化和氧化应激标志物有关。免疫球蛋白G（IgG）和IgA与寄生虫对淋巴结和血液的负担呈正相关。IgG，IgA和IgE水平升高与严重的犬利什曼病（CanL）有关，而未感染的裸犬中IgM升高。IgM，IgG和IgA与血清中肌酐，尿素，AST和ALT水平的相关性提示这些Igs参与了肾脏和肝脏的改变。氧化自由基和抗氧化剂的相关图揭示了IgM，IgG和IgA与血液中的氧化应激和脂质过氧化的可能关系，提示其是介导组织损伤和CanL恶化的机制。与免疫球蛋白种类的定量变化相关的染色体区段上的基因作图确定了与活性氧产生，吞噬体成熟和破裂，游离铁的利用，Th1 / Th2分化和免疫球蛋白清除有关的遗传特征。该发现证明了抗体应答作为CanL发病机理的抗性或敏感性标记和介体的作用。此外，我们确定了候选基因作为针对由VL加剧的抗体反应和寄生引起的损害的治疗的潜在靶标。这些发现证明了抗体应答作为CanL发病机理的耐药性或敏感性标记和介体的作用。此外，我们确定了候选基因作为针对由VL引起的抗体反应加重和寄生引起的损害的治疗的潜在靶标。这些发现证明了抗体应答作为CanL发病机理的耐药性或敏感性标记和介体的作用。此外，我们确定了候选基因作为针对由VL引起的抗体反应加重和寄生引起的损害的治疗的潜在靶标。