Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity


Lausch E., Janecke A., Bros M., Trojandt S., Alanay Y. , De Laet C., et al.

NATURE GENETICS, cilt.43, ss.132-139, 2011 (SCI İndekslerine Giren Dergi)

  • Cilt numarası: 43 Konu: 2
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1038/ng.749
  • Dergi Adı: NATURE GENETICS
  • Sayfa Sayısı: ss.132-139

Özet

Vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases are the hallmarks of the genetic disorder spondyloenchondrodysplasia. We mapped a locus in five consanguineous families to chromosome 19p13 and identified mutations in ACP5, which encodes tartrate-resistant phosphatase (TRAP), in 14 affected individuals and showed that these mutations abolish enzyme function in the serum and cells of affected individuals. Phosphorylated osteopontin, a protein involved in bone reabsorption and in immune regulation, accumulates in serum, urine and cells cultured from TRAP-deficient individuals. Case-derived dendritic cells exhibit an altered cytokine profile and are more potent than matched control cells in stimulating allogeneic T cell proliferation in mixed lymphocyte reactions. These findings shed new light on the role of osteopontin and its regulation by TRAP in the pathogenesis of common autoimmune disorders.