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RESEARCH PRODUCT
Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity
Sylvie TenoutasseLuisa BonaféStefanie TrojandtRaffaele RenellaRaffaele RenellaBernhard ZabelPeter MeineckeCorinne De LaetYasemin AlanaySheila UngerSheila UngerMatthias BrosEkkehart LauschMari MatsuoYoshiko HiranoGen NishimuraAndreas R. JaneckeJürgen W. SprangerChristian A. HübnerAndrea Superti-furgaAndrea Superti-furgaSharon UngerAndrea KissRafael Fabiano Machado Rosasubject
Malemedicine.medical_specialtyLymphocyteT cellAcid PhosphatasePhosphataseAutoimmunityOsteochondrodysplasiasmedicine.disease_causeBone and BonesAutoimmune DiseasesAutoimmunity03 medical and health sciences0302 clinical medicineInternal medicineGeneticsmedicineHumansGenetic Predisposition to DiseaseOsteopontinPhosphorylationChild030304 developmental biologyTartrate-resistant acid phosphatase030203 arthritis & rheumatologyBone Diseases Developmental0303 health sciencesbiologyTartrate-Resistant Acid PhosphataseHomozygoteBrainMetaphyseal dysplasiamedicine.disease3. Good healthIsoenzymesRadiographymedicine.anatomical_structureEndocrinologyDysplasiaMutationbiology.proteinCalciumOsteopontindescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-08-19 | Nature Genetics |