Immunoproteomic Profiling of Antiviral Antibodies in New-Onset Type 1 Diabetes Using Protein Arrays

• Published in: Diabetes (New York, N.Y.) Vol. 65; no. 1; pp. 285 - 296
• Main Authors: Bian, Xiaofang, Wallstrom, Garrick, Davis, Amy, Wang, Jie, Park, Jin, Throop, Andrea, Steel, Jason, Yu, Xiaobo, Wasserfall, Clive, Schatz, Desmond, Atkinson, Mark, Qiu, Ji, LaBaer, Joshua
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.01.2016
• Subjects: Adolescent; Adult; Antibodies, Viral - immunology; Autoantibodies - immunology; Case-Control Studies; Cation Transport Proteins - immunology; Child; Child, Preschool; Coxsackievirus Infections - immunology; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Diabetes; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - virology; Endogenous Retroviruses - immunology; Enterovirus B, Human - immunology; Epstein-Barr virus; Epstein-Barr Virus Infections; Female; Genetics/Genomes/Proteomics/Metabolomics; Glutamate Decarboxylase - immunology; Herpesvirus 4, Human - immunology; High-Throughput Screening Assays; Humans; Immunoglobulins; Male; Mumps - immunology; Mumps virus - immunology; Protein Array Analysis; Proteomics; Rotavirus - immunology; Rotavirus Infections - immunology; Rubella - immunology; Rubella virus - immunology; Viral infections; Viral Proteins - immunology; Viruses; Young Adult; Zinc Transporter 8
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db15-0179

The rapid rise in the incidence of type 1 diabetes (T1D) suggests the involvement of environmental factors including viral infections. We evaluated the association between viral infections and T1D by profiling antiviral antibodies using a high-throughput immunoproteomics approach in patients with new-onset T1D. We constructed a viral protein array comprising the complete proteomes of seven viruses associated with T1D and open reading frames from other common viruses. Antibody responses to 646 viral antigens were assessed in 42 patients with T1D and 42 age- and sex-matched healthy control subjects (mean age 12.7 years, 50% males). Prevalence of antiviral antibodies agreed with known infection rates for the corresponding virus based on epidemiological studies. Antibody responses to Epstein-Barr virus (EBV) were significantly higher in case than control subjects (odds ratio 6.6; 95% CI 2.0–25.7), whereas the other viruses showed no differences. The EBV and T1D association was significant in both sex and age subgroups (≤12 and >12 years), and there was a trend toward early EBV infections among the case subjects. These results suggest a potential role for EBV in T1D development. We believe our innovative immunoproteomics platform is useful for understanding the role of viral infections in T1D and other disorders where associations between viral infection and disease are unclear.