Increased plasma chemokine levels in children with Prader-Willi syndrome

• Published in: American journal of medical genetics. Part A Vol. 167A; no. 3; pp. 563 - 571
• Main Authors: Butler, Merlin G., Hossain, Waheeda, Sulsona, Carlos, Driscoll, Daniel J., Manzardo, Ann M.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2015; Wiley Subscription Services, Inc
• Subjects: bioinflammatory chemokines; Chemokines - blood; Child; Child, Preschool; children; cytokines; Cytokines - blood; Female; Genetic Testing; Humans; immune system; Male; neurodevelopment; Phenotype; Prader-Willi syndrome; Prader-Willi Syndrome - blood; Prader-Willi Syndrome - diagnosis; Prader-Willi Syndrome - genetics; Siblings; bioinflammatory chemokines; immune system; cytokines; Prader-Willi syndrome; neurodevelopment; children
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.36908

Prader–Willi syndrome (PWS) is caused by loss of paternally expressed genes from the 15q11‐q13 region and reportedly rearranged as a cause of autism. Additionally, increased inflammatory markers and features of autism are reported in PWS. Cytokines encoded by genes involved with inflammation, cell proliferation, migration, and adhesion play a role in neurodevelopment and could be disturbed in PWS as abnormal plasma cytokine levels are reported in autism. We analyzed 41 plasma cytokines in a cohort of well‐characterized children with PWS between 5 and 11 years of age and unaffected unrelated siblings using multiplex sandwich immunoassays with the Luminex magnetic‐bead based platform. Data were analyzed using ANOVA testing for effects of diagnosis, gender, body mass index (BMI) and age on the 24 cytokines meeting laboratory criteria for inclusion. No significant effects were observed for age, gender or BMI. The log‐transformed levels of the 24 analyzable cytokines were examined simultaneously using MANOVA adjusting for age and gender and a main effect of diagnosis was found (P‐value <0.03). Four of 24 plasma cytokine levels (MCP1, MDC, Eotaxin, RANTES) were significantly higher in children with PWS compared with controls and classified as bioinflammatory chemokines supporting a disturbed immune response unrelated to obesity status. BMI was not statistically different in the two subject groups (PWS or unaffected unrelated siblings) and chemokine levels were not correlated with percentage of total body fat. Additional studies are required to identify whether possible early immunological disturbances and chemokine inflammatory processes found in PWS may contribute to neurodevelopment and behavioral features. © 2015 Wiley Periodicals, Inc.