MHC class II polymorphism is associated with a canine SLE-related disease complex

Wilbe, Maria; Jokinen, Päivi; Hermanrud, Christina; Kennedy, L. J.; Strandberg, E.; Hansson-Hamlin, Helene; Lohi, Hannes; Andersson, Gerhard

doi:10.1007/s00251-009-0387-6

Cited by 52 publications

(52 citation statements)

References 26 publications

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“…[45][46][47] We 48 and others [49][50][51][52][53][54] have used the anti-mouse/rat Foxp3 antibody clone FJK-16s to identify a population of canine CD4 + T cells that phenotypically resembles Treg cells, but direct evidence for regulatory activity has remained elusive. 55 In this study, we have characterized the phenotype and function of canine CD4 + CD25 high FOXP3 high T cells in vitro, providing direct evidence for the regulatory function of this T-cell subset in dogs -an important veterinary species that also serves as a model for several human diseases, including a number of cancers, [56][57][58] systemic lupus erythematosus 59,60 and several genetic diseases of the haemopoietic system. 61 …”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 97%

Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

et al. 2010

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Summary Relatively little is known about regulatory T (Treg) cells and their functional responses in dogs. We have used the cross‐reactive anti‐mouse/rat Foxp3 antibody clone FJK‐16s to identify a population of canine CD4+ FOXP3high T cells in both the peripheral blood (PB) and popliteal lymph node (LN). FOXP3+ cells in both PB and LN yielded positive staining with the newly developed anti‐murine/human Helios antibody clone 22F6, consistent with the notion that they were naturally occurring Treg cells. Stimulation of mononuclear cells of LN origin with concanavalin A (Con A) in vitro yielded increased proportions and median fluorescence intensity of FOXP3 expression by both CD4+ and CD8+ T cells. Removal of the Con A and continued culture disclosed a CD4+ FOXP3high population, distinct from the CD4+ FOXP3intermediate T cells; very few CD8+ FOXP3high T cells were observed, though CD8+ FOXP3intermediate cells were present in equal abundance to CD4+ FOXP3intermediate cells. The CD4+ FOXP3high T cells were thought to represent activated Treg cells, in contrast to the FOXP3intermediate cells, which were thought to be a more heterogeneous population comprising predominantly activated conventional T cells. Co‐staining with interferon‐γ (IFN‐γ) supported this notion, because the FOXP3high T cells were almost exclusively IFN‐γ−, whereas the FOXP3intermediate cells expressed a more heterogeneous IFN‐γ phenotype. Following activation of mononuclear cells with Con A and interleukin‐2, the 5% of CD4+ T cells showing the highest CD25 expression (CD4+ CD25high) were enriched in cells expressing FOXP3. These cells were anergic in vitro, in contrast to the 20% of CD4+ T cells with the lowest CD25 expression (CD4+ CD25−), which proliferated readily. The CD4+ CD25high FOXP3high T cells were able to suppress the proliferation of responder CD4+ T cells in vitro, in contrast to the CD4+ CD25− cells, which showed no regulatory properties.

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Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 97%

Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

et al. 2010

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“…SRMA has been described as occasionally occurring concurrently with immune-mediated polyarthritis (Webb and others 2002, Tipold and Schatzberg 2010). Genetic studies have indicated an inherited connection between the diseases, IMRD and SRMA, in Tollers (Wilbe and others 2009, 2010).…”

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confidence: 99%

“…In earlier studies of Tollers with both SRMA and the SLE-related disease complex, several genes have been identified and one locus seems to be shared between the disease complexes (Wilbe and others 2009, 2010). Further genetic studies are in progress in order to in more detail identify, validate and functionally define the causative mutations.…”

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confidence: 99%

Steroid‐responsive meningitis‐arteritis in Nova Scotia duck tolling retrievers

Hansson-Hamlin

Lilliehöök

2013

Veterinary Record

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“…A Vogt-Koyanagi-Harada-like syndrome of Akita dogs has a strong association with certain alleles and allele combinations of DLA class II genes, 1 as does autoimmune hemolytic anemia, 20 immune arthritis, 28 hypothyroidism in several breeds, 25,26,38 type I diabetes mellitus in Samoyed dogs and Cairn and Tibetan Terriers, 23 anal furunculosis of German Shepherd Dogs, 5 and systemic lupus erythematosus-related complex of Nova Scotia Tolling Retrievers. 37 Necrotizing meningoencephalitis (NME) of Pug dogs 10 and Addison disease in Nova Scotia Duck Tolling Retrievers 12 have been recently added to this growing list. Dog leukocyte antigen class II associations have also been described for visceral leishmaniasis 30 in domestic dogs in Spain and for generalized demodicosis in Boxer, Argentinean Mastiff, and mixed-breed dogs in Argentina.…”

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confidence: 99%

Dog Leukocyte Antigen Class II–Associated Genetic Risk Testing for Immune Disorders of Dogs: Simplified Approaches Using Pug Dog Necrotizing Meningoencephalitis as a Model

et al. 2011

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Abstract. A significantly increased risk for a number of autoimmune and infectious diseases in purebred and mixed-breed dogs has been associated with certain alleles or allele combinations of the dog leukocyte antigen (DLA) class II complex containing the DRB1, DQA1, and DQB1 genes. The exact level of risk depends on the specific disease, the alleles in question, and whether alleles exist in a homozygous or heterozygous state. The gold standard for identifying high-risk alleles and their zygosity has involved direct sequencing of the exon 2 regions of each of the 3 genes. However, sequencing and identification of specific alleles at each of the 3 loci are relatively expensive and sequencing techniques are not ideal for additional parentage or identity determination. However, it is often possible to get the same information from sequencing only 1 gene given the small number of possible alleles at each locus in purebred dogs, extensive homozygosity, and tendency for disease-causing alleles at each of the 3 loci to be strongly linked to each other into haplotypes. Therefore, genetic testing in purebred dogs with immune diseases can be often simplified by sequencing alleles at 1 rather than 3 loci. Further simplification of genetic tests for canine immune diseases can be achieved by the use of alternative genetic markers in the DLA class II region that are also strongly linked with the disease genotype. These markers consist of either simple tandem repeats or single nucleotide polymorphisms that are also in strong linkage with specific DLA class II genotypes and/or haplotypes. The current study uses necrotizing meningoencephalitis of Pug dogs as a paradigm to assess simple alternative genetic tests for disease risk. It was possible to attain identical necrotizing meningoencephalitis risk assessments to 3-locus DLA class II sequencing by sequencing only the DQB1 gene, using 3 DLA class IIlinked simple tandem repeat markers, or with a small single nucleotide polymorphism array designed to identify breed-specific DQB1 alleles.

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MHC class II polymorphism is associated with a canine SLE-related disease complex

Cited by 52 publications

References 26 publications

Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

Steroid‐responsive meningitis‐arteritis in Nova Scotia duck tolling retrievers

Dog Leukocyte Antigen Class II–Associated Genetic Risk Testing for Immune Disorders of Dogs: Simplified Approaches Using Pug Dog Necrotizing Meningoencephalitis as a Model

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