Detection of interferon alpha protein reveals differential levels and cellular sources in disease

被引：270

作者：

Rodero, Mathieu P. ^{[1
]}

Decalf, Jeremie ^{[3
,5
]}

Bondet, Vincent ^{[3
,5
]}

Hunt, David ^{[6
]}

Rice, Gillian I. ^{[8
]}

Werneke, Scott ^{[3
,5
]}

McGlasson, Sarah L. ^{[6
,7
]}

Alyanakian, Marie-Alexandra ^{[10
]}

Bader-Meunier, Brigitte ^{[11
,15
]}

Barnerias, Christine ^{[12
]}

Bellon, Nathalia ^{[13
]}

Belot, Alexandre ^{[16
]}

Bodemer, Christine ^{[2
,13
]}

Briggs, Tracy A. ^{[8
,9
]}

Desguerre, Isabelle ^{[12
]}

Fremond, Marie-Louise ^{[1
]}

Hully, Marie ^{[12
]}

van den Maagdenberg, Arn M. J. M. ^{[17
,18
]}

Melki, Isabelle ^{[1
,19
]}

Meyts, Isabelle ^{[20
,21
]}

Musset, Lucile ^{[22
]}

Pelzer, Nadine ^{[17
]}

Quartier, Pierre ^{[2
,11
]}

Terwindt, Gisela M. ^{[17
]}

Wardlaw, Joanna ^{[7
]}

Wiseman, Stewart ^{[7
]}

Rieux-Laucat, Frederic ^{[2
]}

Rose, Yoann ^{[1
]}

Neven, Benedicte ^{[2
,15
]}

Hertel, Christina ^{[23
]}

Hayday, Adrian ^{[24
,25
]}

Albert, Matthew L. ^{[3
,4
,5
]}

Rozenberg, Flore ^{[26
]}

Crow, Yanick J. ^{[1
,2
,8
,14
]}

Duffy, Darragh ^{[3
,4
,5
]}

机构：

[1] INSERM, UMR1163, Lab Neurogenet & Neuroinflammat, F-75015 Paris, France

[2] Univ Sorbonne Paris Cite, Univ Paris Descartes, Inst Imagine, F-75015 Paris, France

[3] Inst Pasteur, Immunobiol Dendrit Cells, F-75015 Paris, France

[4] Inst Pasteur, Ctr Translat Res, F-75015 Paris, France

[5] INSERM, U1223, F-75015 Paris, France

[6] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh EH8 9YL, Midlothian, Scotland

[7] Univ Edinburgh, Ctr Clin Brain Sci CCBS, Edinburgh EH8 9YL, Midlothian, Scotland

[8] Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Divis Evolut & Genom Sci, Manchester, Lancs, England

[9] Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Manchester Acad Hlth Sci Ctr, Manchester Ctr Genom Med, Manchester M13 9NT, Lancs, England

[10] Hop Univ Necker Enfants Malades, Lab Immunol Biol, F-75015 Paris, France

[11] Hop Univ Necker Enfants Malades, Pediatr Immunol Hematol & Rheumatol Unit, F-75015 Paris, France

[12] Hop Univ Necker Enfants Malades, Dept Paediat Neurol, F-75015 Paris, France

[13] Hop Univ Necker Enfants Malades, Dept Paediat Dermatol, Reference Ctr Rare Skin Disorders MAGEC, F-75015 Paris, France

[14] Hop Univ Necker Enfants Malades, Assistance Publ Hop Paris, Dept Genet, F-75015 Paris, France

[15] INSERM, UMR 1163, Lab Immunogenet Pediat Autoimmun, F-75015 Paris, France

[16] Hospices Civils Lyon, INSERM, U1111, Dept Paediat Rheumatol, F-69007 Lyon, France

[17] Leiden Univ, Med Ctr, Dept Neurol, NL-2333 ZA Leiden, Netherlands

[18] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands

[19] Robert Debre Hosp, Assistance Publique Hop Paris, Infect Dis & Internal Med Dept, Gen Paediat, F-75019 Paris, France

[20] Univ Hosp Leuven, Dept Pediat, B-3000 Leuven, Belgium

[21] Katholieke Univ Leuven, Dept Microbiol & Immunol, B-3000 Leuven, Belgium

[22] Hop La Pitie Salpetriere, Assistance Publ Hop Paris, Dept Immunol, F-75013 Paris, France

[23] ImmunoQure AG, D-42012 Dusseldorf, Germany

[24] Guys Hosp, Kings Coll, Peter Gorer Dept Immunobiol, London SE1 9RT, England

[25] Francis Crick Inst, London NW1 1BF, England

[26] Univ Sorbonne Paris Cite, Univ Paris Descartes, Grp Hosp Univ Paris Ctr, Assistance Publ Hop Paris,Serv Virol, F-75014 Paris, France

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2017年 / 214卷 / 05期

基金：

欧洲研究理事会; 英国惠康基金; 美国国家卫生研究院;

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; I INTERFERON; INTRATHECAL SYNTHESIS; VIRUS INTERFERENCE; DERMATOMYOSITIS; AUTOANTIBODIES; BLOCKADE; CELLS; ASSAY;

D O I：

10.1084/jem.20161451

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELI SA technology, we recorded attomolar concentrations of IFN alpha in healthy donors, viral infection, and complex and monogenic interferonopathies. IFN alpha protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFN alpha levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFN alpha protein indicated disease-specific mechanisms. Measurement of IFN alpha attomolar concentrations by digital ELI SA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.

引用

页码：1547 / 1555

页数：9

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