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United States Department of Agriculture

Agricultural Research Service

Research Project: NOVEL INTERVENTION STRATEGIES AND GENOMICS FOR CONTROLLING MASTITIS

Location: Animal Genomics and Improvement Laboratory

Title: Evidence for the presence of an autoimmune component to the chronic muscle wasting disease characteristic of calves infected with Aarcocystis cruzi

Authors
item Elsasser, Theodore
item Kahl, Stanislaw
item Fayer, Ronald
item Connor, Erin

Submitted to: Joint Meeting of the ADSA, AMSA, ASAS and PSA
Publication Type: Abstract Only
Publication Acceptance Date: June 10, 2013
Publication Date: June 15, 2013
Citation: Elsasser, T.H., Kahl, S., Fayer, R., Connor, E.E. 2013. Evidence for the presence of an autoimmune component to the chronic muscle wasting disease characteristic of calves infected with Aarcocystis cruzi. J. Anim. Sci. 91: E-Suppl. 2 Program and Abbstracts, 2013 PP. 1.

Technical Abstract: Infection with Sarcocystis spp. often resolves in a progressive decline in muscle integrity. The underlying cause for this has remained undetermined. Previously, we described the presence of proinflammatory muscle protein nitration (PMPN) in calves (ScI) chronically infected with Sarcocystis cruzi. Knowing that instances of PMPN are associated with autoimmune disorders in human muscular atrophy syndromes, we hypothesized that calves infected with Sc might develop autoantibodies consistent with the definition of autoimmune disease. To test this, plasma was collected from 3-mo-old Holstein steers (n = 7) before (D-0) and after (D-55) oral infection with 250,000 Sc oocysts along with contemporary plasmas from noninfected steers (CTL, n = 3). Steers were euthanized on D- 55 and samples of semitendinosus muscle collected as the target for autoantibody reactivity (frozen sections, 6 µ) or homogenate preparation for measurement activity of the proinflammatory marker xanthine oxidase (XO, µU/mg protein). For immunofluorescence detection (IF), slide-mounted serial sections were fixed, permeabilized, blocked, and incubated (12 h, 4C) with each animal’s own D-0 and D-55 plasma (1:80, 1:160, 1:320 in PBS); autoantibody binding was detected with Alexa488-rabbit antibovine IgG. The D-55 average (LSM ± SE) XO activity was 23.5 vs. 129.7 (± 17, P < 0.001) in CTL and ScI, respectively. As detected by IF, the presence of plasma autoantibodies against CTL muscle was not evident with D-0-CTL, D 55-CTL, or D-0-ScI plasmas. All muscle samples from ScI contained cysts. Immunoreactivity of ScI plasma against muscle was evident: 7/7 at 1:80, 4/7 at 1:160, and 2/7 at 1:320. The IHF intensity declined across muscle subcomponents where the signal with cysts > smooth muscle > vascular endothelium > intrafiber proteins. Only plasma from ScI had antinuclear antibodies when incubated with fixed cultured bovine mammary epithelial cells and this signal declined ~70% with DNAase pretreatment. The data are consistent with autoantibody-mediated tissue pathology affecting animal health in this disease paradigm.

Last Modified: 11/21/2014
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