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A study of the immune response in canine disseminated aspergillosis

Day, Michael J. (1987) A study of the immune response in canine disseminated aspergillosis. PhD thesis, Murdoch University.

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Abstract

Disseminated aspergillosis is a recently described disease of the dog. This chronic condition most commonly affects bone and abdominal viscera and is invariably fatal. The largest series of cases so far recorded has been that of the current study which involved 24 dogs predominantly from Western Australia. Dogs in this series were young adults (mean age 3.8 years) and largely of one breed (21 German Shepherd, 2 Dalmatian, 1 Doberman Pinscher). The microorganism involved was either A. terreus (20), A. flavipes (1) or unidentified Aspergillus spp (3). The present research was undertaken to characterize the pathogenesis of disease and the immunocompetence of infected dogs.

A study of general immunocompetence was made in 1? of the affected dogs. This revealed no consistent abnormality in levels of serum immunoglobulin or complement (CH50,C3, C4) with the exception of markedly high IgG in all cases which was shown to be largely specific antibody directed towards A. terreus antigens of molecular weight range 48 - 95 Kdaltons. In the latter stages of disease antibody may be bound in circulating immune complexes but no evidence was obtained to show that these lodged in tissues. The German Shepherd dogs investigated were all related and a number of seropositive healthy relatives were also identified, however there was no disease association with the MHC-linked complement C4 alleles.

No abnormality was detected in neutrophil function (NBT test) of 3 dogs assayed. Some evidence was obtained for depression of cellular immune function, including: depression of intradermal response to A. terreus (3/6 cases), depressed PHA lymphocyte blastogenesis (4/8 cases) and failure of MIF production (1 case). These findings may have been secondary to chronic illness or immunosuppression induced by the fungal metabolite gliotoxin which was shown to affect canine macrophage function. No evidence was found to suggest abnormalities in peripheral blood lymphocyte numbers. There was no T:B lymphocyte imbalance or alteration in percentage of cells reacting with the T cell subset monoclonal antibodies MUI and MUII generated for this study.

Immunohistochemical staining of 25 visceral lesions revealed granuloma formation with central hyphae coated with immunoglobulin (predominantly IgA) and that activation of both classical and alternative complement pathways had occurred. The nature of the perilesional cellular infiltrate varied from acute neutrophilic to The latter cells were largely IgA stained lymphoid cells (also some IgG, IgM, MUII stained) and such cells were chronic mononuclear. also scattered in interstitial tissues. The renal tubular epithelium was also consistently stained by IgA reagent.

These findings together with the demonstration of high levels of circulating SmlgA bearing cells (20%, normal 4%) and a wide variance in serum IgA levels, suggested that a disturbance of IgA regulation was present in these dogs. Clinically normal German Shepherd dogs had a similar wide variance in serum IgA level which was not seen in cross-bred dogs or those of other breed groups.

It is postulated that a failure of mucosal immunity as a consequence of IgA dysregulation may be a common occurrence in this breed and an important contributory factor to the development of disseminated aspergillosis and other diseases.

Item Type: Thesis (PhD)
Murdoch Affiliation: School of Veterinary Studies
Notes: Note to the author: If you would like to make your thesis openly available on Murdoch University Library's Research Repository, please contact: repository@murdoch.edu.au. Thank you.
Supervisor(s): Penhale, William
URI: http://researchrepository.murdoch.edu.au/id/eprint/53232
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