Comparative and correlative assessments of cytokine, complement and antibody patterns in paediatric type 1 diabetes

Clin Exp Immunol. 2017 Oct;190(1):110-121. doi: 10.1111/cei.13001. Epub 2017 Jul 13.


One of the most widespread and effective environmental factors is the infection with enteroviruses (EVs) which accelerate β cell destruction in type 1 diabetes (T1D). This study represented a comparison between diabetic EV+ and EV- children as well as correlation analysis between autoantibodies, T1D markers, cytokines, complement activation products and anti-coxsackievirus (CV) immunoglobulin (Ig)G. EV RNA was detected in Egyptian children with T1D (26·2%) and healthy controls (0%). Detection of anti-CV IgG in T1D-EV+ resulted in 64% positivity. Within T1D-EV+ , previously diagnosed (PD) showed 74 versus 56% in newly diagnosed (ND) children. Comparisons between populations showed increased levels of haemoglobin A1c (HbA1c), C-reactive protein (CRP), nitric oxide (NO), glutamic acid decarboxylase and insulin and islet cell autoantibodies [glutamic acid decarboxylase autoantibodies (GADA), insulin autoantibodies (IAA) and islet cell cytoplasmic autoantibodies (ICA), respectively], interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL -10, IL -12, IL -17, C3d and sC5-9 in T1D-EV+ versus T1D-EV- . Conversely, both IL-20 and transforming growth factor (TGF-β) decreased in T1D-EV+ versus EV- , while IL-4, -6 and -13 did not show any changes. Correlation analysis showed dependency of accelerated autoimmunity and β cell destruction on increased IFN-γ, IL-12 and IL-17 versus decreased IL-4, -6 and -13. In conclusion, IFN-γ, IL-12 and IL-17 played an essential role in exacerbating EV+ -T1D, while C3d, sC5b -9, IL-10 and -20 displayed distinct patterns.

Keywords: complement; correlation; cytokines; enteroviruses; type 1 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Antibodies, Viral / metabolism
  • Apoptosis
  • Autoantibodies / metabolism
  • Child
  • Child, Preschool
  • Complement Activation
  • Complement C3d / metabolism
  • Complement C5b / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / immunology*
  • Egypt
  • Enterovirus / immunology*
  • Enterovirus Infections / complications
  • Enterovirus Infections / immunology*
  • Glutamate Decarboxylase / immunology
  • Humans
  • Insulin / immunology
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology


  • Antibodies, Viral
  • Autoantibodies
  • Cytokines
  • Insulin
  • Complement C3d
  • Complement C5b
  • Glutamate Decarboxylase