Endocrine Abstracts

Background: Addison’s disease (AD) in both humans and dogs is characterised by corticosteroid deficiency requiring lifelong hormone therapy. In humans autoimmune pathogenesis is established; at diagnosis ~90% of patients are 21-hydroxylase (21-OH) autoantibody positive, with antibodies to other adrenal antigens also detected. The pathogenesis of canine AD is less well characterised; autoimmune mechanisms are suspected, with anti-adrenal autoantibodies demonstrated by indirect immunofluorescence.

Hypothesis: Specific adrenal autoantibodies are detectable in canine AD patients.

Methods: Canine orthologs of 21-OH, p450 side-chain cleavage enzyme (P450scc), 3-β-hydroxysteroid dehydrogenase (3-β-HSD) and 17-α-hydroxylase (17-α-OH) were identified, cloned and S³⁵ radiolabelled recombinant proteins expressed. A RIA was validated using radiolabelled human 21-OH and sera of known autoantibody status. Sera from AD dogs and controls with no history of an endocrinopathy or immune-mediated disease were then tested to investigate the presence of autoantibodies; cross-reactivity across species was also assessed.

Results: Radiolabelled proteins were of expected size. Human 21-OH autoantibodies did not cross-react with the canine radiolabelled protein. A proportion, 5/20, of canine AD samples showed reactivity to P450scc, these were a German Shepherd Dog, Beagle, Lurcher, Great Dane and Polish Lowland Sheepdog, comprising three females and two males. Human P450scc autoantibody positive sera from a patient with autoimmune polyglandular syndrome type one (APS1) and a patient with APS2 with associated premature ovarian failure (POF) cross-reacted with canine P450scc.

Conclusions: This is the first study showing P450scc autoantibodies in canine AD. This offers interesting comparisons with human disease, in particular with APS1 and POF, both associated with P450scc autoantibodies. These findings help confirm an immune-mediated component to canine AD, a potential model for the human disease, and could offer a new approach for diagnostic testing in dogs.

Declaration of funding: This work was supported by the BBSRC with Dechra (grant number BB/G016992/1) and the PetPlan Charitable Trust (grant number 09-04).