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

Tracy A Briggs; Gillian I Rice; Sarah Daly; Jill Urquhart; Hannah Gornall; Brigitte Bader-Meunier; Kannan Baskar; Shankar Baskar; Veronique Baudouin; Michael W Beresford; Graeme C M Black; Rebecca J Dearman; Francis de Zegher; Emily S Foster; Camille Francès; Alison R Hayman; Emma Hilton; Chantal Job-Deslandre; Muralidhar L Kulkarni; Martine Le Merrer; Agnes Linglart; Simon C Lovell; Kathrin Maurer; Lucile Musset; Vincent Navarro; Capucine Picard; Anne Puel; Frederic Rieux-Laucat; Chaim M Roifman; Sabine Scholl-Bürgi; Nigel Smith; Marcin Szynkiewicz; Alice Wiedeman; Carine Wouters; Leo A H Zeef; Jean-Laurent Casanova; Keith B Elkon; Anthony Janckila; Pierre Lebon; Yanick J Crow

doi:10.1038/ng.748

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

Tracy A Briggs, Gillian I Rice, Sarah Daly, Jill Urquhart, Hannah Gornall, Brigitte Bader-Meunier, Kannan Baskar, Shankar Baskar, Veronique Baudouin, Michael W Beresford, Graeme C M Black, Rebecca J Dearman, Francis de Zegher, Emily S Foster, Camille Francès, Alison R Hayman, Emma Hilton, Chantal Job-Deslandre, Muralidhar L Kulkarni, Martine Le MerrerAgnes Linglart, Simon C Lovell, Kathrin Maurer, Lucile Musset, Vincent Navarro, Capucine Picard, Anne Puel, Frederic Rieux-Laucat, Chaim M Roifman, Sabine Scholl-Bürgi, Nigel Smith, Marcin Szynkiewicz, Alice Wiedeman, Carine Wouters, Leo A H Zeef, Jean-Laurent Casanova, Keith B Elkon, Anthony Janckila, Pierre Lebon, Yanick J Crow

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	127-31
Number of pages	5
Journal	Nature Genetics
Volume	43
Issue number	2
DOIs	https://doi.org/10.1038/ng.748
Publication status	Published - Feb 2011

Keywords / Materials (for Non-textual outputs)

Acid Phosphatase
Animals
Autoimmunity
Bone Diseases, Developmental
Cattle
Chromosomes, Human, Pair 19
Female
Gene Expression Regulation
Humans
Inflammation
Interferon Type I
Isoenzymes
Lupus Erythematosus, Systemic
Male
Models, Molecular
Mutation
Mutation, Missense
Phenotype
Sclerosis
Tartrate-Resistant Acid Phosphatase
Journal Article
Research Support, Non-U.S. Gov't

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10.1038/ng.748

Cite this

Briggs, T. A., Rice, G. I., Daly, S., Urquhart, J., Gornall, H., Bader-Meunier, B., Baskar, K., Baskar, S., Baudouin, V., Beresford, M. W., Black, G. C. M., Dearman, R. J., de Zegher, F., Foster, E. S., Francès, C., Hayman, A. R., Hilton, E., Job-Deslandre, C., Kulkarni, M. L., ... Crow, Y. J. (2011). Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nature Genetics, 43(2), 127-31. https://doi.org/10.1038/ng.748

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

abstract = "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, Sj{\"o}gren'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.",

keywords = "Acid Phosphatase, Animals, Autoimmunity, Bone Diseases, Developmental, Cattle, Chromosomes, Human, Pair 19, Female, Gene Expression Regulation, Humans, Inflammation, Interferon Type I, Isoenzymes, Lupus Erythematosus, Systemic, Male, Models, Molecular, Mutation, Mutation, Missense, Phenotype, Sclerosis, Tartrate-Resistant Acid Phosphatase, Journal Article, Research Support, Non-U.S. Gov't",

author = "Briggs, {Tracy A} and Rice, {Gillian I} and Sarah Daly and Jill Urquhart and Hannah Gornall and Brigitte Bader-Meunier and Kannan Baskar and Shankar Baskar and Veronique Baudouin and Beresford, {Michael W} and Black, {Graeme C M} and Dearman, {Rebecca J} and {de Zegher}, Francis and Foster, {Emily S} and Camille Franc{\`e}s and Hayman, {Alison R} and Emma Hilton and Chantal Job-Deslandre and Kulkarni, {Muralidhar L} and {Le Merrer}, Martine and Agnes Linglart and Lovell, {Simon C} and Kathrin Maurer and Lucile Musset and Vincent Navarro and Capucine Picard and Anne Puel and Frederic Rieux-Laucat and Roifman, {Chaim M} and Sabine Scholl-B{\"u}rgi and Nigel Smith and Marcin Szynkiewicz and Alice Wiedeman and Carine Wouters and Zeef, {Leo A H} and Jean-Laurent Casanova and Elkon, {Keith B} and Anthony Janckila and Pierre Lebon and Crow, {Yanick J}",

year = "2011",

month = feb,

doi = "10.1038/ng.748",

language = "English",

volume = "43",

pages = "127--31",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

Briggs, TA, Rice, GI, Daly, S, Urquhart, J, Gornall, H, Bader-Meunier, B, Baskar, K, Baskar, S, Baudouin, V, Beresford, MW, Black, GCM, Dearman, RJ, de Zegher, F, Foster, ES, Francès, C, Hayman, AR, Hilton, E, Job-Deslandre, C, Kulkarni, ML, Le Merrer, M, Linglart, A, Lovell, SC, Maurer, K, Musset, L, Navarro, V, Picard, C, Puel, A, Rieux-Laucat, F, Roifman, CM, Scholl-Bürgi, S, Smith, N, Szynkiewicz, M, Wiedeman, A, Wouters, C, Zeef, LAH, Casanova, J-L, Elkon, KB, Janckila, A, Lebon, P & Crow, YJ 2011, 'Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature', Nature Genetics, vol. 43, no. 2, pp. 127-31. https://doi.org/10.1038/ng.748

TY - JOUR

T1 - Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature

AU - Briggs, Tracy A

AU - Rice, Gillian I

AU - Daly, Sarah

AU - Urquhart, Jill

AU - Gornall, Hannah

AU - Bader-Meunier, Brigitte

AU - Baskar, Kannan

AU - Baskar, Shankar

AU - Baudouin, Veronique

AU - Beresford, Michael W

AU - Black, Graeme C M

AU - Dearman, Rebecca J

AU - de Zegher, Francis

AU - Foster, Emily S

AU - Francès, Camille

AU - Hayman, Alison R

AU - Hilton, Emma

AU - Job-Deslandre, Chantal

AU - Kulkarni, Muralidhar L

AU - Le Merrer, Martine

AU - Linglart, Agnes

AU - Lovell, Simon C

AU - Maurer, Kathrin

AU - Musset, Lucile

AU - Navarro, Vincent

AU - Picard, Capucine

AU - Puel, Anne

AU - Rieux-Laucat, Frederic

AU - Roifman, Chaim M

AU - Scholl-Bürgi, Sabine

AU - Smith, Nigel

AU - Szynkiewicz, Marcin

AU - Wiedeman, Alice

AU - Wouters, Carine

AU - Zeef, Leo A H

AU - Casanova, Jean-Laurent

AU - Elkon, Keith B

AU - Janckila, Anthony

AU - Lebon, Pierre

AU - Crow, Yanick J

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

KW - Acid Phosphatase

KW - Animals

KW - Autoimmunity

KW - Bone Diseases, Developmental

KW - Cattle

KW - Chromosomes, Human, Pair 19

KW - Female

KW - Gene Expression Regulation

KW - Humans

KW - Inflammation

KW - Interferon Type I

KW - Isoenzymes

KW - Lupus Erythematosus, Systemic

KW - Male

KW - Models, Molecular

KW - Mutation

KW - Mutation, Missense

KW - Phenotype

KW - Sclerosis

KW - Tartrate-Resistant Acid Phosphatase

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ng.748

DO - 10.1038/ng.748

M3 - Article

C2 - 21217755

SN - 1061-4036

VL - 43

SP - 127

EP - 131

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

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