A plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease, whereas type 2 diabetes (T2D) results from insulin resistance and beta cell dysfunction. Previously, the onset of these two separate diseases was easily distinguished, with children being most at risk for T1D and T2D occurring in overweight adults. However, the dramatic rise in obesity, coupled with the notable increase in T1D, has created a large overlap in these previously discrete patient populations. Delayed diagnosis of T1D can result in severe illness or death, and rapid diagnosis of T1D is critical for the efficacy of emerging therapies. However, attempts to apply next-generation platforms have been unsuccessful for detecting diabetes biomarkers. Here we describe the development of a plasmonic gold chip for near-infrared fluorescence–enhanced (NIR-FE) detection of islet cell–targeting autoantibodies. We demonstrate that this platform has high sensitivity and specificity for the diagnosis of T1D and can be used to discover previously unknown biomarkers of T1D.

[1]  M. Rewers,et al.  Distinguishing Persistent Insulin Autoantibodies With Differential Risk , 2011, Diabetes.

[2]  Joseph R Lakowicz,et al.  Radiative decay engineering 5: metal-enhanced fluorescence and plasmon emission. , 2005, Analytical biochemistry.

[3]  M. Wabl,et al.  Hypermutation in antibody affinity maturation. , 1999, Current opinion in immunology.

[4]  M. Bentley,et al.  Chemistry for peptide and protein PEGylation. , 2002, Advanced drug delivery reviews.

[5]  D. Doniach,et al.  Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. , 1974, Lancet.

[6]  H. Kolb,et al.  Insulin autoantibodies measured by radioimmunoassay methodology are more related to insulin-dependent diabetes mellitus than those measured by enzyme-linked immunosorbent assay: results of the Fourth International Workshop on the Standardization of Insulin Autoantibody Measurement. , 1992, The Journal of clinical endocrinology and metabolism.

[7]  P. Bingley,et al.  Combined testing of antibody titer and affinity improves insulin autoantibody measurement: Diabetes Antibody Standardization Program. , 2007, Clinical immunology.

[8]  Michael Schlosser,et al.  Diabetes Antibody Standardization Program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and islet antigen-2 , 2008, Diabetologia.

[9]  P. Bingley,et al.  Diabetes Antibody Standardization Program , 2011, Diabetes Care.

[10]  P. Bingley,et al.  Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies , 2010, Diabetologia.

[11]  P. Zeitler.  Approach to the obese adolescent with new-onset diabetes. , 2010, The Journal of clinical endocrinology and metabolism.

[12]  G. Eisenbarth,et al.  Accepting clocks that tell time poorly: fluid-phase versus standard ELISA autoantibody assays. , 2007, Clinical immunology.

[13]  P. Bingley,et al.  Diabetes Antibody Standardization Program: first assay proficiency evaluation. , 2003, Diabetes.

[14]  Darrell M. Wilson,et al.  Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial , 2011, The Lancet.

[15]  Desmond E. Williams,et al.  The Burden of Diabetes Mellitus Among US Youth: Prevalence Estimates From the SEARCH for Diabetes in Youth Study , 2006, Pediatrics.

[16]  P. Mortensen.  EPIDEMIOLOGY , 2012, Schizophrenia Research.

[17]  I. Hirsch,et al.  Animal insulin therapy induces a biased insulin antibody response that persists for years after introduction of human insulin , 2010, Acta Diabetologica.

[18]  H. Dai,et al.  Multiplexed cytokine detection on plasmonic gold substrates with enhanced near-infrared fluorescence , 2013, Nano Research.

[19]  R. Hamman,et al.  Projections of Type 1 and Type 2 Diabetes Burden in the U.S. Population Aged <20 Years Through 2050 , 2012, Diabetes Care.

[20]  D. Schatz,et al.  Through the Fog: Recent Clinical Trials to Preserve β-Cell Function in Type 1 Diabetes , 2012, Diabetes.

[21]  Hongjie Dai,et al.  Plasmonic substrates for multiplexed protein microarrays with femtomolar sensitivity and broad dynamic range. , 2011, Nature communications.

[22]  B. Jansson,et al.  The interaction between different domains of staphylococcal protein A and human polyclonal IgG, IgA, IgM and F(ab')2: separation of affinity from specificity. , 1993, Molecular immunology.

[23]  K. Jones.  Role of Obesity in Complicating and Confusing the Diagnosis and Treatment of Diabetes in Children , 2008, Pediatrics.

[24]  Simon Smyth,et al.  Diabetes and obesity: the twin epidemics , 2006, Nature Medicine.

[25]  C. Beaufort.  Variation and trends in incidence of childhood diabetes in Europe , 2000, The Lancet.

[26]  E. Bonifacio,et al.  Comparison of a novel micro-assay for insulin autoantibodies with the conventional radiobinding assay , 1998, Diabetologia.

[27]  A. Green,et al.  Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study , 2009, The Lancet.

[28]  P. Bingley,et al.  Measurement of islet cell antibodies in the Type 1 Diabetes Genetics Consortium: efforts to harmonize procedures among the laboratories , 2010, Clinical trials.

[29]  David M Maahs,et al.  Epidemiology of type 1 diabetes. , 2010, Endocrinology and metabolism clinics of North America.

[30]  J. Tuomilehto,et al.  Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. , 2000, Diabetes care.