Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease

The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patient...

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Bibliographic Details
Published in:PLoS genetics 2015-06, Vol.11 (6), p.e1005248-e1005248
Main Authors: Wilbe, Maria, Kozyrev, Sergey V, Farias, Fabiana H G, Bremer, Hanna D, Hedlund, Anna, Pielberg, Gerli R, Seppälä, Eija H, Gustafson, Ulla, Lohi, Hannes, Carlborg, Örjan, Andersson, Göran, Hansson-Hamlin, Helene, Lindblad-Toh, Kerstin
Format: Article
Language:English
Subjects:
Animals
Annan veterinärmedicin
Antigens
Autoimmune diseases
Case-Control Studies
Chromosomes
Dogs
Experiments
Gene expression
Genetic Loci
Genetics and Breeding
Genetik och förädling
Genome
Genomes
Haplotypes
Kawasaki disease
Lupus Erythematosus, Systemic - genetics
Lupus Erythematosus, Systemic - veterinary
Meningitis
Other Veterinary Science
Phenotype
Reumatologi och inflammation
Rheumatic diseases
Rheumatology and Autoimmunity
Studies
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Summary:The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAMTOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1005248