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Title: Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)

Author
item SCHULLER, SIMONE - University College Dublin
item CALLANAN, JOHN - University College Dublin
item WORRALL, SHEILA - University College Dublin
item FRANCEY, THIERRY - Vetsuisse Berne
item SCHWEIGHAUSER, ARIANE - Vetsuisse Berne
item KOHN, BARBARA - Free University Of Berlin
item KLOPFLEISCH, ROBERT - Free University Of Berlin
item POSTHAUS, HORST - Vetsuisse Berne
item Nally, Jarlath

Submitted to: Comparative Immunology Microbiology and Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/21/2015
Publication Date: 6/20/2015
Citation: Schuller, S., Callanan, J.J., Worrall, S., Francey, T., Schweighauser, A., Kohn, B., Klopfleisch, R., Posthaus, H., Nally, J.E. 2015. Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS). Comparative Immunology Microbiology and Infectious Diseases. 40:47-53. DOI: 10.1016/j.cimid.2015.04.002.

Interpretive Summary: Leptospirosis is a zoonotic disease of global significance. Clinical symptoms range from a mild fever to severe icteric disease to leptospiral pulmonary haemorrhage syndrome (LPHS). LPHS occurs in humans and dogs, and is the most severe form of leptospirosis with high mortality rates. LPHS has been replicated in a guinea pig model of infection and results suggest that pathogenic mechanisms are mediated in part by the host immune response: deposition of immunoglobulin and complement was detected in lung tissue in the absence of any leptospiral antigen. Similar results were observed when these studies were extended to human lung tissue from patients diagnosed with LPHS. In this manuscript, these studies have been further extended to include lung from dogs with naturally occurring LPHS and have also confirmed the deposition of antibodies in infected lung tissue in the absence of leptospiral antigen. Overall, this indicates that aetiology of LPHS is similar in dogs and humans. Dogs live in human environments, present with similar clinical signs and, in contrast to small laboratory animals, can benefit from advanced treatment options such as haemodialysis and plasmapheresis; this allows for comparative treatment studies. The study of naturally infected dogs therefore represents an important complement to studies in experimentally infected laboratory animals.

Technical Abstract: Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG, IgM and leptospiral antigens. Three staining patterns for IgG/IgM were observed in lungs of dogs with LPHS with most tissues showing more than one staining pattern: (1) alveolar septal wall staining, (2) staining favouring alveolar surfaces and (3) staining of intra-alveolar fluid. Healthy control lung showed no staining, whereas haemorrhagic lung from dogs not infected with Leptospira showed staining of intra-alveolar fluid and occasionally alveolar septa. Leptospiral antigens were not detected. We conclude that deposition of IgG/IgM is demonstrable in the majority of canine lungs with naturally occurring LPHS, similar to what has been described in other species. Our findings support involvement of host humoral immunity in the pathogenesis of LPHS and provide further evidence to support the dog as a natural disease model for human LPHS.