Assessment of Acute-Phase Protein Response Associated with the Different Pathological Forms of Bovine Paratuberculosis

SIMPLE SUMMARY: Paratuberculosis (PTB) is a chronic debilitating disease caused by Mycobacterium avium subspecies paratuberculosis (Map) that affects ruminants worldwide. Many aspects related to the pathogenesis of this disease are still unknown, including the inflammatory acute-phase response developed during the course of the infection. To clarify this, serum levels of haptoglobin and serum amyloid A, two positive acute-phase proteins, were evaluated in a total of 190 cows, among which 59 were healthy control animals and 131 cows were diagnosed post-mortem with different types of lesion associated with Map-infection. The results reflect a significant increase of these proteins’ levels in the infected animals and, more specifically, in those animals with types of lesion characterized by a low bacterial load and with predominance of a cell-mediated immune response. This suggests that these molecules would play a certain role in the pathogenesis of the PTB and a possible utility as biomarkers of different stages of the disease. ABSTRACT: In this study, the concentrations of two acute-phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were quantitatively assessed in serum samples from cattle naturally infected with paratuberculosis (PTB). APP profiles were compared across 190 animals classified according to the different pathological forms associated with infection: uninfected (n = 59), with focal lesions (n = 73), multifocal lesions (n = 19), and diffuse paucibacillary (n = 11) and diffuse multibacillary lesions (n = 28). Our results showed a significant increase in both APPs in infected animals compared to the control group, with differences depending on the type of lesion. Hp and SAA levels were increased significantly in all infected animals, except in cows with diffuse multibacillary lesions that showed similar values to non-infected animals. The expression pattern of both APPs was similar and negatively correlated with the antibody levels against PTB. These results indicate that the release of Hp and SAA is related to the presence of PTB lesions associated with a high cell-mediated immune response and a lower bacterial load, suggesting that the pro-inflammatory cytokines that are associated with these forms are the main stimulus for their synthesis. These molecules could show some potential to be used as putative biomarkers of PTB infection, particularly for the identification of subclinical animals showing pathological forms related to latency or resistance to the development of advanced lesions.