Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature.
Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature.
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DOI：
10.1038/ng.748
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发表时间：
2011-02
期刊：
影响因子：
30.8
通讯作者：
Crow, Yanick J.
中科院分区：
文献类型：
--
作者：
Briggs, Tracy A.;Rice, Gillian I.;Daly, Sarah;Urquhart, Jill;Gornall, Hannah;Bader-Meunier, Brigitte;Baskar, Kannan;Baskar, Shankar;Baudouin, Veronique;Beresford, Michael W.;Black, Graeme C. M.;Dearman, Rebecca J.;de Zegher, Francis;Foster, Emily S.;Frances, Camille;Hayman, Alison R.;Hilton, Emma;Job-Deslandre, Chantal;Kulkarni, Muralidhar L.;Le Merrer, Martine;Linglart, Agnes;Lovell, Simon C.;Maurer, Kathrin;Musset, Lucile;Navarro, Vincent;Picard, Capucine;Puel, Anne;Rieux-Laucat, Frederic;Roifman, Chaim M.;Scholl-Buergi, Sabine;Smith, Nigel;Szynkiewicz, Marcin;Wiedeman, Alice;Wouters, Carine;Zeef, Leo A. H.;Casanova, Jean-Laurent;Elkon, Keith B.;Janckila, Anthony;Lebon, Pierre;Crow, Yanick J.
我们研究了来自8个家族的10个个体，这些个体表现出与免疫骨性发育不良脊柱软骨发育不良（SPENCD）一致的特征。特别值得注意的是在这些患者中观察到的多种自身免疫表型，包括系统性红斑狼疮（SLE）、干燥综合征、溶血性贫血、血小板减少症、甲状腺功能减退症、炎性肌炎、雷诺氏病和白癜风。单倍型数据表明该疾病基因位于染色体19p13上，连锁分析得到了3.6的组合多点lod得分。对编码抗酒石酸酸性磷酸酶（TRAP）的ACP 5基因进行测序，在研究的每个患者中鉴定了双等位基因突变，体内试验证实了表达蛋白的丢失。所有8例患者的血清干扰素α活性升高，全血中的基因表达谱确定了I型干扰素特征。我们的发现揭示了TRAP活性和干扰素代谢之间以前未被认识到的联系，并强调了I型干扰素在自身免疫发生中的重要性。
We studied ten individuals from eight families showing features consistent with the immuno-osseus dysplasia spondyloenchondrodysplasia (SPENCD). Of particular note was the diverse spectrum of autoimmune phenotypes observed in these patients, including systemic lupus erythematosus (SLE), Sjögren's syndrome, haemolytic 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 lod score of 3.6. Sequencing of the ACP5 gene, encoding tartrate resistant acid phosphatase (TRAP), identified biallelic mutations in each of the patients studied, and in vivo testing confirmed a loss of expressed protein. All eight patients assayed demonstrated elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognised link between TRAP activity and interferon metabolism, and highlight the importance of type I interferon in the genesis of autoimmunity.
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影响因子：
64.5
作者：
Stetson DB;Ko JS;Heidmann T;Medzhitov R
通讯作者：
Medzhitov R
影响因子：
2
作者：
Navarro, V.;Scott, C.;Crow, Y. J.
通讯作者：
Crow, Y. J.
影响因子：
5
作者：
Chao, TY;Lee, SH;Janckila, AJ
通讯作者：
Janckila, AJ
影响因子：
5.6
作者：
Sträter, N;Jasper, B;Guss, JM
通讯作者：
Guss, JM
影响因子：
3.7
作者：
Ankel, H;Westra, DF;Lebon, P
通讯作者：
Lebon, P