Plasma cytokine profiles in Fragile X subjects: is there a role for cytokines in the pathogenesis?

Abstract

Background: Fragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement and a strong association with autism. Altered immune responses have been described in autism and there is potential that in children with FXS and autism, an abnormal immune response may play a role.

Objectives: To delineate specific patterns of cytokine/chemokine profiles in individuals with FXS with and without autism and to compare them with typical developing controls.

Methods: Age matched male subjects were recruited through the M.I.N.D. Institute and included: 19 typically developing controls, 64 subjects with FXS without autism and 40 subjects with FXS and autism. Autism diagnosis was confirmed with ADOS, ADI-R and DSM IV criteria. Plasma was isolated and cytokine and chemokine production was assessed by Luminex multiplex analysis.

Results: Preliminary observations indicate significant differences in plasma protein levels of a number of cytokines, including IL-1alpha, and the chemokines; RANTES and IP-10, between the FXS group and the typical developing controls (p<0.01). In addition, significant differences were observed between the FXS group with autism and the FXS without autism for IL-6, eotaxin, MCP-1 (p<0.04).

Conclusions: In this study, the first of its kind, we report a significantly altered cytokine profile in FXS. The characterization of an immunological profile in FXS with and without autism may help to elucidate if an abnormal immune response may play a role and help to identify mechanisms important in the etiology of autism both with and without FXS.

Figure 1

Distribution of IL-1α, IL-6, RANTES and IP-10 among FXS, FXS+AU and typically developing controls (IL-1α: FXS+AU vs. control p = 0.003, FXS vs. control p = 0.009; IL-6: FXS+AU vs. FXS p = 0.007; RANTES: FXS vs. control p < 0.001; IP-10: FXS+AU vs. control p < 0.001; FXS vs. control p < 0.001). y-axis represents cytokine levels in log scale (Log (pg/ml)). Horizontal box lines are 25%, 50% (median) and 75% of the distribution with whiskers marking 1.5 times the interquartile range. Open circles indicate potential outliers. Analysis results with or without these two data points did not differ.