Salivary anti-coxsackievirus-B4 neutralizing activity and pattern of immune parameters in patients with type 1 diabetes: a pilot study

Acta Diabetol. 2018 Aug;55(8):827-834. doi: 10.1007/s00592-018-1158-3. Epub 2018 May 17.

Abstract

Aims: Enteroviruses, especially coxsackieviruses B (CV-B), have been associated with the pathogenesis of type 1 diabetes (T1D). An anti-CV-B4 neutralizing activity in saliva of T1D patients was previously reported. Our aim was to study the association between the saliva anti-CV-B4 neutralizing activity and immune parameters in T1D patients in comparison with non-diabetic individuals.

Methods: Saliva and blood samples were collected from 15 T1D patients and 8 controls. The anti-CV-B4 and anti-poliovirus type 1 (PV-1) activities of saliva and serum samples were determined by a plaque neutralization assay. Quantification of serum cytokines was performed by ELISA and the frequencies of lymphocyte subsets were evaluated using flow cytometry.

Results: The levels of salivary anti-CV-B4 neutralizing activity were higher in T1D patients than in controls (p = 0.02), whereas the serum levels of anti-CV-B4 neutralizing activity and the saliva and serum levels of anti-PV-1 neutralizing activity were not different. The proportions of effector CD4+ T cells and CD19+ B cells, but not those of CD4+ T cells, CD8+ T cells and Foxp3+ regulatory T cells, were higher in T1D patients than in controls (p = 0.02 and p = 0.01 respectively). Moreover, serum IFN-γ levels were lower in T1D patients compared to controls (p = 0.03) while IL-4 and IL-10 were not different. There was an association between saliva anti-CV-B4 activity, down-regulation of IFN-γ and B cell expansion in peripheral blood of T1D patients.

Conclusion: The association between saliva anti-CV-B4 activity and disturbance of immune system in T1D patients deserves further investigation.

Keywords: Cytokines; Enterovirus; Immune cells; Neutralization assay; Saliva; Type 1 diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Neutralizing / metabolism*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Coxsackievirus Infections / complications
  • Coxsackievirus Infections / immunology*
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / immunology*
  • Enterovirus B, Human / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunity, Innate / physiology*
  • Interleukin-10 / metabolism
  • Male
  • Neutralization Tests
  • Pilot Projects
  • Saliva / immunology*
  • Saliva / metabolism
  • Vero Cells
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Cytokines
  • IL10 protein, human
  • Interleukin-10