Interferon gamma responses to proteome-determined specific recombinant proteins: Potential as diagnostic markers for ovine Johne's disease

Abstract

Johne's disease (JD), or paratuberculosis is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). There may be a long subclinical phase with no signs of clinical disease. Diagnosis of JD is problematic and no test can reliably detect sub-clinical disease. Th1 responses to Map are believed to be activated first with a later switch to Th2 responses and progression to clinical disease. Detection of a cell-mediated response, indicated by interferon gamma (IFN-γ) produced in response to mycobacterial antigens, may give an early indication of infection. Crude extracts of Map (PPDj) have been used to detect the cell-mediated response, but more specific, quantifiable antigens would improve the test. Thirty Map-specific proteins were screened for their ability to raise a cell-mediated response in subclinically infected sheep. Four proteins were selected and tested using blood from subclinical animals and controls from a JD-free flock. Three proteins elicited IFN-γ levels which were higher in the subclinical group than in the control group, two were statistically significant. Thus these proteins have the ability to discriminate groups of infected and uninfected animals and may have use in diagnosis of JD.

Lymphoproliferative and Gamma Interferon Responses to Stress-Regulated Mycobacterium avium subsp. paratuberculosis Recombinant Proteins

“…The findings suggest that not all M. avium subsp. paratuberculosis proteins known to be differentially regulated under stress conditions are of potential diagnostic value, as found by other studies (33,34). There is a need to investigate other M. avium subsp.…”

Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens

“…During recent years, several recombinant proteins or peptides derived from MAP were evaluated in experimental and field studies using cattle and sheep in an attempt to replace PPDj with more specific antigens (12)(13)(14)(15)(16)(17)(18). Promising protein antigen candidates have been identified, for example Map 3651c and Map 0268c.…”

Interferon gamma response to Mycobacterium avium subsp. paratuberculosis specific lipopentapeptide antigen L5P in cattle

“…The classical response pattern to mycobacteria infection involves firstly a T helper (Th) 1 response which then switches to a Th2 response (Stabel, 2000(Stabel, , 2006. The IFN-γ release assay (IGRA) takes advantage of this by assessing the cell mediated immune (CMI) response to purified protein derivatives (PPDs) (Jungersen et al, 2011) or recombinant antigens selected for their specificity (Gurung et al, 2014;Hughes et al, 2013;Mikkelsen et al, 2011a). This method requires antigens capable of eliciting a sensitive and specific response, and which are currently under investigation (Mikkelsen et al, 2011b).…”