Serological autoantibody profiling of type 1 diabetes by protein arrays

Shane Miersch, Xiaofang Bian, Garrick Wallstrom, Sahar Sibani, Tanya Logvinenko, Clive H. Wasserfall, Desmond Schatz, Mark Atkinson, Ji Qiu, Joshua LaBaer

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)486-496
Number of pages11
JournalJournal of Proteomics
Volume94
DOIs
StatePublished - Dec 6 2013

Fingerprint

Protein Array Analysis
Medical problems
Type 1 Diabetes Mellitus
Autoantibodies
Autoantigens
Proteins
Biomarkers
Nucleic Acids
Screening
Microarrays
Autoimmune Diseases
Genes
Antigens
Validation Studies
Proteome
Luciferases
Immunoprecipitation
Area Under Curve
Early Diagnosis
Assays

Keywords

  • Autoantibody
  • NAPPA
  • Protein array
  • Type 1 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

Miersch, S., Bian, X., Wallstrom, G., Sibani, S., Logvinenko, T., Wasserfall, C. H., ... LaBaer, J. (2013). Serological autoantibody profiling of type 1 diabetes by protein arrays. Journal of Proteomics, 94, 486-496. https://doi.org/10.1016/j.jprot.2013.10.018

Serological autoantibody profiling of type 1 diabetes by protein arrays. / Miersch, Shane; Bian, Xiaofang; Wallstrom, Garrick; Sibani, Sahar; Logvinenko, Tanya; Wasserfall, Clive H.; Schatz, Desmond; Atkinson, Mark; Qiu, Ji; LaBaer, Joshua.

In: Journal of Proteomics, Vol. 94, 06.12.2013, p. 486-496.

Research output: Contribution to journalArticle

Miersch, S, Bian, X, Wallstrom, G, Sibani, S, Logvinenko, T, Wasserfall, CH, Schatz, D, Atkinson, M, Qiu, J & LaBaer, J 2013, 'Serological autoantibody profiling of type 1 diabetes by protein arrays', Journal of Proteomics, vol. 94, pp. 486-496. https://doi.org/10.1016/j.jprot.2013.10.018
Miersch S, Bian X, Wallstrom G, Sibani S, Logvinenko T, Wasserfall CH et al. Serological autoantibody profiling of type 1 diabetes by protein arrays. Journal of Proteomics. 2013 Dec 6;94:486-496. https://doi.org/10.1016/j.jprot.2013.10.018
Miersch, Shane ; Bian, Xiaofang ; Wallstrom, Garrick ; Sibani, Sahar ; Logvinenko, Tanya ; Wasserfall, Clive H. ; Schatz, Desmond ; Atkinson, Mark ; Qiu, Ji ; LaBaer, Joshua. / Serological autoantibody profiling of type 1 diabetes by protein arrays. In: Journal of Proteomics. 2013 ; Vol. 94. pp. 486-496.
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