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Canine immune-mediated disease

studies of epidemiology, genetics, and autoantibodies

Bremer, Hanna (2018). Canine immune-mediated disease. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880 ; 2018:13
ISBN 978-91-7760-166-1
eISBN 978-91-7760-167-8
[Doctoral thesis]

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Immune-mediated diseases in dogs constitute a large group of disorders with the common attribute that they are caused by dysfunctions in the immune system. Broadly they can be classified into immunodeficiency disorders, allergies, and autoimmune diseases. Earlier studies have suggested that dogs of the breed Nova Scotia duck tolling retriever (NSDTR) are at increased risk of developing immune-mediated disorders. Two disorders have received particular attention: immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). The major aims of this thesis were to 1) determine the incidence of immune-mediated disease in NSDTRs, 2) identify genetic risk factors for IMRD and SRMA, and 3) investigate the occurrence of different autoantibodies in dogs with autoimmune disease.

Data from Agria Pet Insurance were used to estimate incidence of disease. Incidence of different immune-mediated diseases in NSDTRs was compared with that in other dog breeds. In general, the incidence for autoimmune diseases was three times higher in NSDTRs compared to other breeds. For IMRD and SRMA, the incidences were >10 times higher.

Both IMRD and SRMA are complex genetic diseases and several genetic loci associated with the respective disease have been identified by our research group. We performed a detailed analysis of these loci and found 11 genes with altered gene expression associated with IMRD or SRMA. The majority of these genes were associated with either IMRD or with SRMA only, but one gene (AP3B2) showed association to both diseases.

Autoantibodies are important hallmarks of autoimmune diseases, including IMRD. In the studies presented in this thesis, different methods were used to identify the autoantibody targets in dogs that were positive for antinuclear autoantibodies. Both previously reported and new canine autoantibodies were found. The interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) appear to be common autoantibody targets in IMRD patients. These autoantibodies have not previously been described in dogs and have the potential to be used as diagnostic markers for canine systemic autoimmune disease.

Authors/Creators:Bremer, Hanna
Title:Canine immune-mediated disease
Subtitle:studies of epidemiology, genetics, and autoantibodies
Alternative abstract:

Immunmedierade sjukdomar hos hund består av en stor grupp av olika åkommor. Gemensamt är att de orsakas av defekter i immunförsvaret. Generellt kan de delas in i immunbristsjukdomar, allergier och autoimmuna sjukdomar. Tidigare studier har antytt att hundar av rasen Nova Scotia duck tolling retriever (kallade tollare) har en ökad risk att utveckla immunmedierade sjukdomar. Det är framförallt två sjukdomar som uppmärksammats hos rasen: immunmedierad reumatisk sjukdom (IMRD) och steroid-responsiv meningit-arterit (SRMA). De huvudsakliga syftena med denna avhandling var att 1) beskriva incidensen av immunmedierade sjukdomar hos tollare, 2) identifiera genetiska riskfaktorer för IMRD och SRMA hos tollare och 3) undersöka förekomst av olika autoantikroppar hos hundar med autoimmun sjukdom.

Data från Agria Djurförsäkring användes för att uppskatta sjukdomsincidens. Incidensen av olika immunmedierade sjukdomar hos tollare undersöktes och jämfördes med incidensen hos hundar av andra raser. Autoimmuna sjukdomar var tre gånger vanligare hos tollare jämfört med andra hundraser. Incidensen för IMRD och SRMA var >10 gånger högre.

Både IMRD och SRMA är komplexa genetiska sjukdomar. Flera regioner i arvsmassan associerade med dessa sjukdomar har tidigare identifierats. Vi utförde en detaljerad uppföljningsanalys av dessa regioner och hittade 11 gener associerade med IMRD eller SRMA som visade förändrat genuttryck. De flesta av dessa gener var associerade med bara en av sjukdomarna, men en gen (AP3B2) var associerad med båda sjukdomarna.

Autoantikroppar är viktiga kännetecken för autoimmuna sjukdomar såsom IMRD. I studierna som presenteras i denna avhandling användes olika metoder för att detektera de målstrukturer som antinukleära autoantikropparna är riktade mot. Både tidigare beskrivna och nya autoantikroppar hos hund identifierades. Autoantikroppar mot interleukin enhancer-binding factor 2 och 3 (ILF2 och ILF3) var vanligt förekommande hos hundar med IMRD. Dessa autoantikroppar har inte beskrivits tidigare hos hund och har potential att kunna användas som diagnostiska markörer för systemisk autoimmun sjukdom hos hund.

Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :April 2018
Depositing date:19 April 2018
Number of Pages:67
IBremer HD, Vilson Å, Bonnett BN, Hansson-Hamlin H (2015). Disease patterns and incidence of immune-mediated disease in insured Swedish Nova Scotia Duck Tolling Retrievers. Veterinary Record, 177 (3), p. 74.
IIWilbe M, Kozyrev SV, Farias FHG, Bremer HD, Hedlund A, Pielberg GR, Seppälä EH, Gustafson U, Lohi H, Carlborg Ö, Andersson G, Hansson-Hamlin H, Lindblad-Toh K (2015). Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease. PLOS Genetics, 11 (6), e1005248.
IIIBremer HD, Lattwein E, Renneker S, Lilliehöök I, Rönnelid J, Hansson-Hamlin H (2015). Identification of specific antinuclear antibodies in dogs using a line immunoassay and enzyme-linked immunosorbent assay. Veterinary Immunology and Immunopathology, 168 (3-4) pp. 233-241.
IVBremer HD, Landegren N, Sjöberg R, Hallgren Å, Renneker S, Lattwein E, Leonard D, Eloranta M-L, Rönnblom L, Nordmark G, Nilsson P, Andersson G, Lilliehöök I, Lindblad-Toh K, Kämpe O, Hansson-Hamlin H (2018). ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease. Scientific Reports, 8(1), p.4852
Place of Publication:Uppsala
Publisher:Department of Clinical Sciences, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-7760-166-1
ISBN for electronic version:978-91-7760-167-8
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Agrovoc terms:dogs, autoimmune diseases, autoimmunity, antibodies, immunological factors, arthritis, gene expression, animal diseases
Keywords:Antinuclear antibodies, autoimmunity, dog, gene expression, ILF2, ILF3, immune-mediated rheumatic disease, Nova Scotia duck tolling retriever, steroid-responsive meningitis-arteritis, systemic lupus erythematosus
Permanent URL:
ID Code:15432
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
External funders:Agria and Uppsala University and Swedish Research Council
Deposited By: H.D. Bremer
Deposited On:25 Apr 2018 10:05
Metadata Last Modified:09 Sep 2020 14:17

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