Circulating immune complexes levels correlate with the progression of canine leishmaniosis in naturally infected dogs

Abstract

Dogs are the main domestic reservoir of Leishmania infantum, and in cases of uncontrolled infection, a strong humoral immune response is elicited, which is inefficient against the parasites. Previous studies have suggested that an adequate antigen/antibody ratio, with a moderate prevalence of antigens with respect to the antibodies, could result in the formation of circulating immune complexes (CIC) in canine leishmaniosis (CanL). Deposition of these complexes in tissues has been associated with vasculitis, uveitis, arthritis, dermatitis and especially glomerulonephritis and renal failure. However, little is known about the relationship between the presence of CIC and disease progression. The aim of this study was to evaluate serum CIC level and its correlation with disease severity in infected dogs with different stages of disease and non-infected animals as a control. A total of 60 dogs were included in the study, classified according to the proposed LeishVet classification criteria: healthy non-infected (n = 13); healthy infected (n = 12); sick stage I (n = 9); sick stage II (n = 17); sick stage III (n = 8); and sick stage IV (n = 1). CIC were isolated from serum samples using a modified polyethylene glycol precipitation method, and their levels measured by ELISA and bicinchoninic acid protein assay. A nanoparticle tracking analysis was performed to investigate the relationship between the molecular size distribution of the CIC and disease progression. In conclusion, the results confirmed a positive association between CIC levels, their molecular size and disease progression that suggests a potential use of CIC as biomarkers of CanL.

Latest trends in L. infantum infection in dogs in Spain, Part II: current clinical management and control according to a national survey of veterinary practitioners

“…In the present study, weight loss, lymphadenomegaly and exfoliative dermatitis were frequently observed in agreement with the findings of other studies and surveys [25,26,[44][45][46][47]. While renal disease, vasculitis, ocular and join disease have been observed less frequently, these are indicators of a worse prognosis because they are clinical signs related to immunocomplex deposition [48][49][50][51][52]. Additionally, other clinical signs have been sporadically observed such as neurological signs [53][54][55][56][57] or digestive disorders [58][59][60].…”

Latest trends in L. infantum infection in dogs in Spain (Part II): current clinical management and control according to a national survey in practitioners

“…In the present study, weight loss, lymphadenomegaly and exfoliative dermatitis were frequently observed in agreement with the findings of other studies and surveys [25,26,40,41,42,43]. While renal disease, vasculitis, ocular and join disease have been less frequently observed, these are indicators of a worse prognosis because they are clinical signs related to immunocomplex deposition [44,45,46,47,48]. Besides, other clinical signs have been sporadically observed such as neurological signs [49,50,51,52,53] or digestive disorders [54,55,56].…”

Assessment of Circulating Immune Complexes During Natural and Experimental Canine Leishmaniasis

“…Immune-mediated mechanisms play a pivotal role in the pathogenesis of many clinical manifestations of CanL, particularly in the development of four principal types of glomerulonephritis, characterized by different grade of proteinuria and responsible for the development of renal failure, the most severe complication of CanL. Previous studies found a significant correlation between the level of antibody titers when assessed by IFAT and the severity of the disease (18)(19)(20), while a recent paper (21) demonstrated that CICs concentration is clearly related to the progression of CanL in naturally-infected dogs. In this study, remarkable was the demonstration of larger-size CICs (ranging from 100 to 400 nm) formed during the worsening of the disease, which was also characterized by an increase of IFAT titers.…”

“…This is quite different if compared with the probable acute stimulation due to the single intravenous injection of millions of parasites typical of an experimental infection. For this reason we believe important not only to assess the level of CICs during different stages of disease (21), but also to correlate the observed CICs levels with the time spent from the first demonstration of infection. The present study demonstrated also the usefulness of the ELISA kit for CICs detection.…”

“…This test is easy to perform and does not require sophisticated instruments. A limit could be related to the generic (aspecific) assessment of CICs, independently from the pathogen that caused them or their molecular size (21). This limitation could be important, mainly in case of concomitant infectious disease(s).…”