Comparative analysis of the Leishmania infantum-specific antibody repertoires and the autoantibody repertoires between asymptomatic and symptomatic dogs

Abstract

Leishmania (L.) infantum-infected dogs may present with a large range of clinical signs, from apparently healthy with no or few (asymptomatic dogs, AD) to several clinical signs indicators of active infection (symptomatic dogs, SD). The present study is justified by the conflicting reports describing that either L. infantum-specific IgG1 or IgG2 antibodies may be used as isotype marker of the asymptomatic infection status and by the lack, to our knowledge, of previous analysis of the IgG sub-classes autoantibody repertoires of Leishmania-infected dogs. On the basis of clinical evaluation and laboratory testing (IFAT, parasitological examination of Giemsa-stained lymph node smears, L. infantum antigens-ELISA of total (Tot) IgG), 131 dogs were categorized as SD, asymptomatic seronegative (AND) or seropositive dogs (APD) from surrounding areas, and as negative control dogs (CTD). ELISA based on leishmanial native antigens or recombinant LACK and LeIF proteins showed that SD produce higher levels of specific Tot IgG, IgG1 and IgG2 antibodies than APD, and that for both clinical stages, the antibody titers of IgG2 isotype were constantly higher than those of the IgG1. The seroprevalences of Tot IgG, IgG2 did not differ between APD and SD groups (97 and 97% in SD; 100 and 96% in APD, respectively) whereas that of IgG1 was slightly lower in SD (88% of APD versus 82% of SD). The autoantibody repertoires were analyzed by ELISA using HEp-2 extracts, ds-DNA, human albumin and transferrin as self-antigens and by Western blot using HEp-2 proteins. ELISA results' indicated that APD develop higher levels of IgG1 autoantibodies, and higher seroprevalence (50% and 26% in APD and SD, respectively), contrasting with lower levels and seroprevalences of Tot IgG and IgG2 (43 and 68% for APD; 100 and 74% for SD). Interestingly, SD showed a stronger IgG1 and particularly IgG2 reactivity with transferrin, an iron-binding protein, than APD and AND. Western blotting experiments produced heterogeneous IgG1 and IgG2 inter- and intra-groups reactivity profiles towards HEp-2 proteins, to identify a specific antigenic profile. Generated data from competitive HEp-2-ELISA using leishmanial antigens as inhibitors were in favor that IgG1 antibodies are predominantly autoantibodies to self-antigens in APD whereas they are mainly cross-reactive (Leishmania/self-antigens) in SD.

Clinical leishmaniosis in a captive Eurasian otter (Lutra lutra) in Spain: a case report

“…The diagnosis of clinical leishmaniosis described in this report was demonstrated by serological and molecular results, similar to a previous report describing the first case of L. infantum infection in a domestic ferret ( Mustela putorius furo ) in Spain [ 3 ]. In dogs, the serum total levels of anti- Leishmania IgG, IgG1 and IgG2 are elevated during the active phase of Leishmania infection, the IgG2 being the predominant subclass [ 12 , 13 ]. At this moment, elevated levels of anti- Leishmania IgG2 in serum were found, as previously reported in dogs with clinical leishmaniosis using TR-IFMA [ 6 ].…”

Canine leishmaniosis and kidney disease: Q&A for an overall management in clinical practice

“…2006) and the production of antinuclear (Lucena & Ginel 1998, Chaabouni et al . 2018), anti‐histone (Ginel et al . 2008), anti‐myofibre (Brandonisio et al .…”

“…A range of tissue autoantibodies may be induced in dogs with leishmaniosis, with possible mechanisms for their induction including polyclonal B-cell activation, inappropriate Th2-mediated activation of autoreactive B lymphocytes, release of autoantigens following tissue damage or molecular mimicry between parasite or sand fly salivary antigens and host autoantigens (Day 2011). The ensuing plasma cell secretion of autoantibodies contributes to immunemediated haemolysis (Ciaramella et al 1997) and thrombocytopenia (Terrazzano et al 2006) and the production of antinuclear , Chaabouni et al 2018, anti-histone (Ginel et al 2008), anti-myofibre (Brandonisio et al 1990, Vamvakidis et al 2000 and peripheral antineutrophil cytoplasmic antibodies (Karagianni et al 2012). In dogs with Leishmaniaassociated pemphigus foliaceus, the pathogenesis likely involves triggering of autoantibody, which binds to interepithelial desmosomal proteins within the epidermis.…”

An Overview of Immunotherapeutic Approaches Against Canine Visceral Leishmaniasis: What Has Been Tested on Dogs and a New Perspective on Improving Treatment Efficacy

“…Moreover, a pronounced anti-Leishmania humoral response leads to the production of high levels of non-immunoprotective antibodies (Barbiéri, 2006;Gradoni, 2015), highlighting the polyclonal B cell response characteristic of susceptibility in CVL (Koutinas and Koutinas, 2014). There is still no consensus as to which IgG subclass is related to resistance or susceptibility in CVL (Lima et al, 2017;Chaabouni et al, 2018). Furthermore, excessive activation of humoral immunity may lead to the production of autoantibodies (Koutinas and Koutinas, 2014), such as antiactin and antitubulin (Pateraki et al, 1983), antinuclear (Smith et al, 2004;Ginel et al, 2008), and antitransferrin (Chaabouni et al, 2018).…”

“…There is still no consensus as to which IgG subclass is related to resistance or susceptibility in CVL (Lima et al, 2017;Chaabouni et al, 2018). Furthermore, excessive activation of humoral immunity may lead to the production of autoantibodies (Koutinas and Koutinas, 2014), such as antiactin and antitubulin (Pateraki et al, 1983), antinuclear (Smith et al, 2004;Ginel et al, 2008), and antitransferrin (Chaabouni et al, 2018).…”