Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature
| Autor: | Jill E. Urquhart, Marcin Szynkiewicz, Anthony J. Janckila, Kannan Baskar, Brigitte Bader-Meunier, Anne Puel, Jean-Laurent Casanova, Martine Le Merrer, Tracy A Briggs, Kathrin Maurer, Shankar Baskar, Capucine Picard, Emily S. Foster, Sarah B. Daly, Vincent Navarro, Véronique Baudouin, Simon C. Lovell, Francis de Zegher, Rebecca J. Dearman, M. L. Kulkarni, Keith B. Elkon, Gillian I. Rice, Agnès Linglart, Emma Hilton, Carine Wouters, Chaim M. Roifman, Alice E. Wiedeman, Frédéric Rieux-Laucat, Sabine Scholl-Bürgi, Camille Francès, Hannah Gornall, Leo A. H. Zeef, Alison R. Hayman, Yanick J. Crow, Michael W. Beresford, Pierre Lebon, Graeme C.M. Black, Nigel Smith, Chantal Job-Deslandre, Lucile Musset |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Hemolytic anemia
Male Models Molecular Acid Phosphatase Mutation Missense Alpha interferon Autoimmunity medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Humans Lupus Erythematosus Systemic 030304 developmental biology Tartrate-resistant acid phosphatase Inflammation 0303 health sciences Bone Diseases Developmental Lupus erythematosus Sclerosis biology Tartrate-Resistant Acid Phosphatase Acid phosphatase medicine.disease 3. Good health Isoenzymes Phenotype Gene Expression Regulation Dysplasia Immunology Interferon Type I Mutation biology.protein Cattle Female Chromosomes Human Pair 19 Interferon type I 030215 immunology medicine.drug |
| Zdroj: | Nature Genetics; Vol 43 Nature Genetics Nature genetics |
| ISSN: | 1061-4036 |
| DOI: | 10.1038/ng.748 |
| Popis: | 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, Sjogren'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. |
| Databáze: | OpenAIRE |
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