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

Abstract

Summary 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.