Autoantigen microarrays for multiplex characterization of autoantibody responses

被引:547
作者
Robinson, WH [1 ]
DiGennaro, C
Hueber, W
Haab, BB
Kamachi, M
Dean, EJ
Fournel, S
Fong, D
Genovese, MC
de Vegvar, HEN
Skriner, K
Hirschberg, DL
Morris, RI
Muller, S
Pruijn, GJ
van Venrooij, WJ
Smolen, JS
Brown, PO
Steinman, L
Utz, PJ
机构
[1] Stanford Univ, Sch Med, Dept Med, Div Rheumatol & Immunol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA
[5] Tolerion, Palo Alto, CA USA
[6] Van Andel Res Inst, Grand Rapids, MI USA
[7] CNRS, Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France
[8] Univ Vienna, Dept Internal Med 3, Div Rheumatol, Vienna, Austria
[9] Rheumatol Diagnost Lab, Los Angeles, CA USA
[10] Katholieke Univ Nijmegen, Dept Biochem, Nijmegen, Netherlands
关键词
D O I
10.1038/nm0302-295
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We constructed miniaturized autoantigen arrays to perform large-scale multiplex characterization of autoantibody responses directed against structurally diverse autoantigens, using submicroliter quantities of clinical samples. Autoantigen microarrays were produced by attaching hundreds of proteins, peptides and other biomolecules to the surface of derivatized glass slides using a robotic arrayer. Arrays were incubated with patient serum, and spectrally resolvable fluorescent labels were used to detect autoantibody binding to specific autoantigens on the array. We describe and characterize arrays containing the major autoantigens in eight distinct human autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. This represents the first report of application of such technology to multiple human disease sera, and will enable validated detection of antibodies recognizing autoantigens including proteins, peptides, enzyme complexes, ribonucleoprotein complexes, DNA and post-translationally modified antigens. Autoantigen microarrays represent a powerful tool to study the specificity and pathogenesis of autoantibody responses, and to identify and define relevant autoantigens in human autoimmune diseases.
引用
收藏
页码:295 / 301
页数:7
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