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Serological autoantibody profiling of type 1 diabetes by protein arrays.

Abstract：

UNLABELLED:The need for biomarkers that illuminate the pathophysiology of type 1 diabetes (T1D), enhance early diagnosis and provide additional avenues for therapeutic intervention is well recognized in the scientific community. We conducted a proteome-scale, two-stage serological AAb screening followed by an independent validation study. In the first stage, the immunoreactivity was compared between T1D cases and healthy controls against ~6000 human proteins using the nucleic acid programmable protein array (NAPPA). Genes identified with higher signal intensities in patients were challenged with a larger sample set during the second stage. Statistical analysis revealed 26 novel autoantigens and a known T1D-associated autoantigen. During validation, we verified the presence of AAbs to dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) using the Luciferase ImmunoPrecipitation System (LIPS) assay (36% sensitivity, 98% specificity). The AUC for a combination of DYRK2A and the classical T1D AAb IA-2A was 0.90 compared to 0.72 for DYRK2A and 0.64 for IA-2A alone. This is the first systematic screening for seroreactivity against a large number of human proteins in T1D patients. We demonstrated the application of protein microarrays to identify novel autoantigens in T1D, expanded the current T1D "autoantigenome" and help fulfill the goal of searching for novel biomarker candidates for T1D. BIOLOGICAL SIGNIFICANCE:Protein microarrays provide a high-throughput platform that enables the profiling of serum antibodies to a large number of protein antigens. The value of AAb biomarkers in diagnosis, prognosis and treatment is well recognized in autoimmune diseases including T1D. We performed a systematic screening for new T1D-associated autoantigens by adapting the innovative protein array platform NAPPA. We believe that the discovery in this study will add information on candidate autoantigens that could potentially improve the diagnosis and help uncover the pathophysiology of T1D. The successful use of NAPPA for T1D AAb profiling will open the window for larger studies including more human antigen genes and other autoimmune diseases.

journal_name

J Proteomics

journal_title

Journal of proteomics

authors

Miersch S,Bian X,Wallstrom G,Sibani S,Logvinenko T,Wasserfall CH,Schatz D,Atkinson M,Qiu J,LaBaer J

doi

10.1016/j.jprot.2013.10.018

subject

Has Abstract

pub_date

2013-12-06 00:00:00

pages

486-96

eissn

1874-3919

issn

1876-7737

pii

S1874-3919(13)00530-7

journal_volume

pub_type

杂志文章,多中心研究,随机对照试验

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Serological autoantibody profiling of type 1 diabetes by protein arrays.