Carriers of the fragile X mental retardation 1 (FMR1) premutation allele present with increased levels of cytokine IL-10.
BACKGROUND
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited late-onset neurodegenerative disorder, characterized both by neurological and cognitive deficits. It is caused by the expansion of CGG repeats (55 to 200 repeats) in the noncoding region of the fragile X mental retardation 1 (FMR1) gene. Abnormal immunological patterns are often associated with neurodegenerative disorders and implicated in their etiology. We therefore investigated the immune status of FXTAS patients, which had not been assessed prior to this study.


METHODS
Peripheral blood mononuclear cells (PBMCs) were collected from 15 asymptomatic FMR1 premutation carriers and 20 age-matched controls. Concentrations of three cytokines (IL-6, IL-8, IL-10) were measured in PBMC supernatants using ELISA assays.


RESULTS
We found a significant increase in the concentration of the major anti-inflammatory cytokine IL-10 in supernatants of PBMCs derived from premutation carriers, when compared with controls (P = 0.019). This increase correlated significantly with the number of CGG repeats (P = 0.002).


CONCLUSIONS
Elevated IL-10 levels were observed in all premutation carriers, before appearance of the classical neurological symptoms; therefore, IL-10 may be one of the early biomarkers of FXTAS.
Department of Medical Genetics, University of Lausanne, Rue du Bugnon 27, Lausanne, 1005, Switzerland.
Diana
D
Marek
Stephanie
S
Papin
Kim
K
Ellefsen
Julien
J
Niederhauser
Nathalie
N
Isidor
Adriana
A
Ransijn
Lucienne
L
Poupon
Francois
F
Spertini
Giuseppe
G
Pantaleo
Sven
S
Bergmann
Jacques S
JS
Beckmann
Sebastien
S
Jacquemont
Goranka
G
Tanackovic
D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D016022:Case-Control Studies; D016207:Cytokines; D004797:Enzyme-Linked Immunosorbent Assay; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012720:Severity of Illness Index; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D016207:Cytokines; D051860:Fragile X Messenger Ribonucleoprotein 1; D016753:Interleukin-10