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, 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.
authors.affiliation: Manchester Academic Heath Science Centre, University of Manchester, Genetic Medicine, Manchester, UK.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Briggs
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.forename: Sarah
authors.initials: S
authors.lastname: Daly
authors.forename: Jill
authors.initials: J
authors.lastname: Urquhart
authors.forename: Hannah
authors.initials: H
authors.lastname: Gornall
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: Kannan
authors.initials: K
authors.lastname: Baskar
authors.forename: Shankar
authors.initials: S
authors.lastname: Baskar
authors.forename: Veronique
authors.initials: V
authors.lastname: Baudouin
authors.forename: Michael W
authors.initials: MW
authors.lastname: Beresford
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Black
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
authors.forename: Emily S
authors.initials: ES
authors.lastname: Foster
authors.forename: Camille
authors.initials: C
authors.lastname: Francès
authors.forename: Alison R
authors.initials: AR
authors.lastname: Hayman
authors.forename: Emma
authors.initials: E
authors.lastname: Hilton
authors.forename: Chantal
authors.initials: C
authors.lastname: Job-Deslandre
authors.forename: Muralidhar L
authors.initials: ML
authors.lastname: Kulkarni
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Agnes
authors.initials: A
authors.lastname: Linglart
authors.forename: Simon C
authors.initials: SC
authors.lastname: Lovell
authors.forename: Kathrin
authors.initials: K
authors.lastname: Maurer
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.forename: Vincent
authors.initials: V
authors.lastname: Navarro
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Frederic
authors.initials: F
authors.lastname: Rieux-Laucat
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
authors.forename: Sabine
authors.initials: S
authors.lastname: Scholl-Bürgi
authors.forename: Nigel
authors.initials: N
authors.lastname: Smith
authors.forename: Marcin
authors.initials: M
authors.lastname: Szynkiewicz
authors.forename: Alice
authors.initials: A
authors.lastname: Wiedeman
authors.forename: Carine
authors.initials: C
authors.lastname: Wouters
authors.forename: Leo A H
authors.initials: LA
authors.lastname: Zeef
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Keith B
authors.initials: KB
authors.lastname: Elkon
authors.forename: Anthony
authors.initials: A
authors.lastname: Janckila
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
mesh_terms: D000135:Acid Phosphatase / Q000172:deficiency* / Q000235:genetics*; D000818:Animals; D015551:Autoimmunity; D001848:Bone Diseases, Developmental / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D002417:Cattle; D002888:Chromosomes, Human, Pair 19; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007370:Interferon Type I / Q000378:metabolism*; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D012598:Sclerosis / Q000473:pathology; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007370:Interferon Type I; D007527:Isoenzymes; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase