Salivary anti-coxsackievirus-B4 neutralizing activity and pattern of immune parameters in patients with type 1 diabetes: a pilot study
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.
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.
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.
The association between saliva anti-CV-B4 activity and disturbance of immune system in T1D patients deserves further investigation.
KeywordsEnterovirus Saliva Neutralization assay Immune cells Cytokines Type 1 diabetes
This work was supported by Ministère de l’Education Nationale de la Recherche et de la Technologie, Université Lille 2 (Equipe d’accueil 3610), Centre Hospitalier Régional et Universitaire de Lille, Institut des Sciences Biomédicales Appliquées (ISBA) and Université d’Abomey-Calavi (République du Benin). We thank Institut de Recherche pour le Développement (IRD-UMR216) and CERPAGE (Centre d’Etude et de Recherche sur le Paludisme associé à la Grossesse et à l’Enfance) who provided the flow cytometry platform. M. P. N was supported by a “CABRI 2016” scholarship of Université Lille 2 and a “Programme Eiffel 2017” scholarship of Ministère des Affaires étrangères et du Développement international de la République Française.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 12.Racaniello VR (2013) Picornaviridae: the viruses and their replication. In: Fields virology. Philadelphia, PA, USA, pp 453–490Google Scholar
- 23.Sane F, Caloone D, Gmyr V et al (2013) Coxsackievirus B4 can infect human pancreas ductal cells and persist in ductal-like cell cultures which results in inhibition of Pdx1 expression and disturbed formation of islet-like cell aggregates. Cell Mol Life Sci 70:4169–4180. https://doi.org/10.1007/s00018-013-1383-4 CrossRefPubMedGoogle Scholar
- 29.Zhu J, Yamane H, Paul W (2010) Differentiation of effector CD4 T cell populations. Annu Rev Immunol 28:445–489. https://doi.org/10.1146/annurev-immunol-030409-101212.Differentiation CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Hamari S, Kirveskoski T, Glumoff V et al (2016) Analyses of regulatory CD4+ CD25+ FOXP3+ T cells and observations from peripheral T cell subpopulation markers during the development of type 1 diabetes in children. Scand J Immunol 83:279–287. https://doi.org/10.1111/sji.12418 CrossRefPubMedPubMedCentralGoogle Scholar