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

Sammanfattning

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 (ANAH) and speckled ANA (ANAS) 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.

Nyckelord

Systemic-Lupus-Erythematosus; responsive meningitis-arteritis; Domain-peptide complex; BANK1 gene; Kawasaki-disease; Pain syndrome; Susceptibility

Publicerad i

PLoS Genetics
2015, volym: 11, nummer: 6, artikelnummer: e1005248

SLU författare

• Wilbe, Maria

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Bremer, Hanna

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

• Hedlund, Anna

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Gustafson, Ulla

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Carlborg, Örjan

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

• Andersson, Göran

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Hamlin, Helene

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Genetik och förädling
Reumatologi och inflammation
Annan veterinärmedicin

Publikationens identifierare

• DOI: https://doi.org/10.1371/journal.pgen.1005248

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/69259