Immune-mediated disease in Nova Scotia Duck Tolling Retriever

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1 Nova Scotia Duck Tolling Retriever Helene Hansson Hamlin, Dep. of Small Animal Clinical Sciences The immune system directed towards the body s own tissue, self To some extent normal reaction In association with tumours, drugs etc. Autoantibodies ANA = antinuclear antibodies Uppsala, Sweden Autoimmuna/immunmedierade sjukdomar Allmänt Autoimmune reaction disease Autoantibodies, abnormal levels: Important for the development of the disease??? Diagnostic marker? B cell Etiology??? Genetics Other factors? Infections, hormones, drugs, certain inflam disorders, factors in the surroundings Age Gender Breed Hemolytic anemia, IMHA Thrombocytopenia, IMTP Autoimmune rheumatic diseases (including toller disease ) Skin disorders, Pemphigus complex Hypothyroidism Myasthenia gravis Addison s disease Diabetes? others... Systemic rheumatic diseases, non erosive Systemic lupus erythematosus, related diseases (Systemic rheumatic diseases, erosive: For example rheumatoid arthritis) Organ specific non organ specific 1

2 Systemisk lupus erythematosus Non-erosive polyarthritis Circulating autoantibodies towards several different structures, for example antigens in cell nuclei Varying clinical signs Systemisk lupus erythematosus Examples of clinical signs: Symmetrical, non-erosive polyarthritis (myositis), stiffness, waxing and waning Skin lesions Fever Blood changes: anaemia, thrombocytopenia Glomerulinephritis ANA test Homogeneous pattern ANA test Speckled pattern fluorescein antiserum autoantibody (patient serum) substrate on glass slide Systemisk lupus erythematosus, DIAGNOSIS Clinical signs ( classification criteria in humans) ANA-test (Coomb s test when anaemia???) Exclude other causes Other ANA-positive rheumatic diseases, -related Mainly affects joints Polyarthritis as in Different subgroups of these diseases, may be differentiated by laboratory techniques but not clinically 2

3 Immune-mediated disease in Nova Scotia Duck Tolling Retriever Immune-mediated disease Uniform disease complex? Unknown etiology The Toller project start 2003! Clinical description of the disease Immunological studies Genetic studies in cooperation with Molecular Animal Genetics, SLU; Broad, USA and Folkhälsan Institute of Genetics, Finland Mainly two different manifestations: Rheumatic disease with chronic musculoskeletal signs or Meningitis with pain from the neck Rheumatic disease with chronic musculoskeletal signs Stiffness after resting, less apparent after exercise Shifting lameness, different legs/joints, unwilling to climb stairs, jump into cars Sometimes other concurrent changes: fever, skin problems Initial signs 2-6 years Another group of NSDTRs: Meningitis pain of the neck, high fever stiffness, depression, anorexia Initial signs usually under one year of age DIAGNOSIS rheumatic disease: Clinical signs g Often ANA pos Elimination of other diagnoses Two different diseases or part of the same disease complex??? 3

4 DIAGNOSIS meningitis ( SRMA ): Clinical signs ANA negative Spinal tap (CSF analysis) Sometimes inflammatory blood changes (unspecific) Elimination of other diagnoses TREATMENT Guarded prognosis NSAID: Mild cases of rheumatic disease Immunosuppr. drugs: Corticosteroids as first choice (Sometimes other drugs) Relapses are common! Other immune-mediated diseases: NSDTRs are over-represented? Addison? Others? Different approaches of the research: Clinical description of the disease; IMRD and SRMA Genetic studies Functional studies studies of expression of genes and their interactions Immunological studies, IFN, other cytokines, other immunological features Comparative studies, humans Genetic studies Aim: To identify genetic risk factors for IMRD and SRMA MHC class II identified for IMRD 3 other strong regions identified d for IMRD 1 shared region for IMRD and SRMA EDTA-blod, DNA GWA, fine mapping, re-sequencing Functional studies Studies of expression of genes Studying RNA in stead of DNA Investigating complex interactions of gene products in the tissue. Fresh blood samples from dogs in an acute phase of the disease, without treatment 4

5 Comparative studies, humans Aim: using the dog as a model in order to find risk factors for humans with corresponding diseases Analyses of candidate genes in the human genome, using gene information from dogs. Cooperation with Lars Rönnblom, UU, and Juha Kere, KI. TOLLARSJUKA The project is still running! We are always interested in blood samples (serum and EDTA) from tollers with suspected toller disease! ANA-analyses of IMRD dogs (special referral form) Functional studies before treatment, fresh blood samples, in special blood tubes. 5

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