Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature

Nat Genet. 2011 Feb;43(2):127-31. doi: 10.1038/ng.748. Epub 2011 Jan 9.


We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sjögren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / deficiency*
  • Acid Phosphatase / genetics*
  • Animals
  • Autoimmunity
  • Bone Diseases, Developmental / enzymology
  • Bone Diseases, Developmental / genetics*
  • Bone Diseases, Developmental / pathology*
  • Cattle
  • Chromosomes, Human, Pair 19
  • Female
  • Gene Expression Regulation*
  • Humans
  • Inflammation
  • Interferon Type I / metabolism*
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics*
  • Lupus Erythematosus, Systemic / metabolism
  • Male
  • Models, Molecular
  • Mutation
  • Mutation, Missense
  • Phenotype
  • Sclerosis / pathology
  • Tartrate-Resistant Acid Phosphatase


  • Interferon Type I
  • Isoenzymes
  • ACP5 protein, human
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase