Evidence of altered salivary cytokine concentrations in Rett syndrome and associations with clinical severity

Breanne J Byiers; Alyssa M Merbler; Chantel C Barney; Kristin A Frenn; Angela Panoskaltsis-Mortari; Michael J Ehrhardt; Timothy J Feyma; Arthur A Beisang; Frank Symons

doi:10.1016/j.bbih.2019.100008

Evidence of altered salivary cytokine concentrations in Rett syndrome and associations with clinical severity

Brain Behav Immun Health. 2019 Nov 14:1:100008. doi: 10.1016/j.bbih.2019.100008. eCollection 2020 Jan.

Authors

Breanne J Byiers¹, Alyssa M Merbler¹, Chantel C Barney², Kristin A Frenn², Angela Panoskaltsis-Mortari³, Michael J Ehrhardt³, Timothy J Feyma², Arthur A Beisang², Frank Symons¹

Affiliations

¹ Department of Educational Psychology, 56 E River Rd, University of Minnesota, Minneapolis, MN, 55455, USA.
² Gillette Children's Specialty Healthcare, 200 University Ave E, St. Paul, Minnesota, 55101, USA.
³ Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, 2450 Riverside Ave, University of Minnesota, Minneapolis, MN, 55454, USA.

Abstract

Background: Immune dysregulation may play a role in the development of Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations of the MECP2 gene. Abnormal cytokine concentrations have been documented in the serum of individuals with RTT. Measurement of salivary cytokines has been investigated as a potential alternative approach to measurement in blood and serum, but it is unclear whether salivary cytokine concentrations can provide valid information about systemic immune function in neurodevelopmental disorders. The goal of this study was to evaluate the potential validity of salivary cytokines as biomarkers of immune dysregulation in RTT.

Methods: Saliva samples from 16 individuals with RTT (all female; age range 2-40 years) and 16 healthy control females (age range 2-40 years) were analyzed for concentrations of 12 cytokines. Between-group differences in concentrations, and correlations with clinical severity in the RTT group were evaluated.

Results: Concentrations of several salivary cytokines (IL-1β, IL-6, IL-8, IL-10, GM-CSF, TNF-α, and VEGF) were increased in RTT compared to controls. The same cytokines showed significant positive correlations with clinical severity scores. There were no differences in concentrations of IL-2, IL-4, IL-5, IL-12p70, and IFN-γ.

Conclusion: The results suggest that salivary cytokines may be a possible indicator of immune dysregulation in RTT. Future research should investigate whether these results can be applied to other neurodevelopmental disorders.

Keywords: Biomarkers; Cytokines; MECP2; Rett syndrome; Saliva.