Serum amyloid A levels and alpha 2 and gamma globulins on serum protein electrophoresis in cats exposed to and infected with Leishmania infantum

Abstract

Background Dogs are the main reservoir hosts of Leishmania infantum; nevertheless, recent investigations indicate a likely role for cats in the epidemiology of Leishmania infection. Feline leishmaniosis (FeL) remains poorly characterised, partly due to the lack of suitable diagnostic tools. This study aimed to compare serum amyloid A (SAA) levels and serum protein electrophoresis (SPE) profiles (specifically, alpha 2 and gamma globulins) in cats naturally exposed to or infected by L. infantum from southern Italy versus those of healthy controls and versus cats with neoplastic or inflammatory conditions from non-endemic areas. Methods Serum or plasma samples from four cohorts of cats were analysed for SAA levels and by SPE: (i) G1: healthy controls from Leishmania-non-endemic regions of Switzerland; (ii) G2: cats pre-diagnosed with neoplastic or inflammatory conditions available from the University of Cambridge sample archive; (iii) G3: L. infantum-seropositive, quantitative (q)PCR-negative cats from southern Italy; (iv) G4: L. infantum-seropositive and qPCR-positive cats from southern Italy. SAA data were assessed for normality and homoscedasticity using the Shapiro–Wilk and Levene’s tests, respectively; the Kruskall–Wallis test, followed by Dunn’s test with Bonferroni correction were subsequently used to compare SAA serum levels between groups. A weighted generalised linear model with a binomial distribution was used to assess statistically significant differences in the numbers of animals displaying elevated gamma globulins and increased alpha 2 globulins between groups. Results Overall, 68 samples were analysed (G1: n = 16, G2: n = 20, G3: n = 20, G4: n = 12). Cats suffering from neoplastic and inflammatory conditions (G2 ) showed significantly higher SAA levels than healthy controls (G1) (median values [interquartile range]: G1: 0.00 [0.00–0.00] mg/l versus G2: 0.85 [0.00–49.55] mg/l). G2, G3 and G4 cats showed higher percentages of individuals with increased alpha 2 globulins (percentages ± standard error: G1 = 20.0% ± 10.3, G2 = 80.0% ± 8.9, G3 = 70.0% ± 10.2, G4 = 75.0% ± 12.5) and gamma globulins (G1 = 0.0% ± 0, G2 = 65.0% ± 10.7, G3 = 50.0% ± 11.2, G4 = 58.3% ± 14.2) than healthy control cats (G1). For all three markers, no significant difference between cats within G2, G3 and G4 was recorded. Conclusions This study indicates that the proportions of animals with elevated levels of alpha 2 and gamma globulins are significantly higher in cats exposed to and infected with L. infantum. Levels of SAA and alpha 2 and gamma globulins may not be used to differentiate between L. infantum infection or exposure, and neoplastic and/or inflammatory conditions. Graphic Abstract

Review and statistical analysis of clinical management of feline leishmaniosis caused by Leishmania infantum

“…In comparison to CanL, there is limited information about clinicopathological abnormalities associated with L. infantum infection in cats [ 41 , 57 , 97 ]. Of the cases analyzed here, hyperproteinemia (46.3%) was the most frequent laboratory abnormality, and hypergammaglobulinemia (71.0%) followed by hypoalbuminemia (19.1%) were the most frequent alterations seen on serum protein electrophoresis, in agreement with the results of two studies [ 41 , 57 ], but in contrast with those of another study [ 58 ].…”

“…The percentages of cats presenting with neutrophilia, thrombocytopenia, proteinuria, and azotemia (18%, 16.6%, 15.2% and 14.9%, respectively) reported in the present study suggest that leishmaniosis should be a differential diagnosis for hypergammaglobulinemic cats with any of these conditions. However, although gamma globulin levels were significantly elevated in FeL, they could not be used to differentiate FeL from other inflammatory, neoplastic or vector-borne diseases in cats [ 97 ]. Furthermore, we report here the important finding that, in FeL, unlike in CanL, azotemia and proteinuria are frequently concurrent [ 98 – 100 ].…”

Feline Leishmaniosis: An Emerging Public Health Problem

“…As for dogs, interferon gamma (IFN-γ) analysis in cat's blood could provide a better estimation of cat exposure to the disease when it is associated to serological and molecular tests [48,82]. Recently, Savioli et al (2021) and Urbani et al (2020) showed that elevated levels of amyloid A, gamma globulins, and alpha 2 globulins could be a good indicator of disease in cats [83,84], although more studies will be necessary to find definitive markers of disease.…”

Serum protein electrophoretogram profile detected in apparently healthy cats infected with Leishmania infantum – Short communication

“…However, the description of the serum protein electrophoresis and the pattern detected in cats infected with L. infantum is variable. Some authors detected monoclonal gammopathy in a cat with clinical disease (Pennisi et al, 2004), while other authors detected polyclonal gammopathy (Fernández-Gallego et al, 2020;Savioli et al, 2021).…”