Plasma cytokine profiles in Fragile X subjects: Is there a role for cytokines in the pathogenesis?
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Impaired immune responses in FXS astrocytes are consistent with previously found dysregulation of several pro-inflammatory cytokines in Fmr1 KO mice and in clinical studies of FXS.
“Impaired immune responses in FXS astrocytes are consistent with previously found dysregulation of several pro-inflammatory cytokines in Fmr1 KO mice24 and in clinical studies of FXS39,53.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [39]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuroglial activation and neuroinflammation in the brain of patients with autism
Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005) · Annals of Neurology · doi:10.1002/ana.20315 · Cited by 2,149 · cited 2× · see citing works
“These include reports of neuroglial activation and neuroinflammation in the CNS, with elevated cytokine responses including IL-6 and TNFa in the brains of individuals with autism spectrum disorders (Garbett et al., 2008; Vargas et al., 2005), as well as the increased presence of plasma antibodies reactive to neuronal…”
BackgroundMaternal influenza infection causes marked behavioral and pharmacological changes in the offspring
Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00297.2003 · Cited by 1,025 · see citing works
The immune response in autism: a new frontier for autism research
Ashwood, P., Wills, S., & Van de Water, J. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.1205707 · Cited by 528 · see citing works
Self-citationImmune transcriptome alterations in the temporal cortex of subjects with autism
Garbett, K., Ebert, P. J., Mitchell, A., Lintas, C., Manzi, B., Mirnics, K., & Persico, A. M. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.01.012 · Cited by 375 · cited 2× · see citing works
“These include reports of neuroglial activation and neuroinflammation in the CNS, with elevated cytokine responses including IL-6 and TNFa in the brains of individuals with autism spectrum disorders (Garbett et al., 2008; Vargas et al., 2005), as well as the increased presence of plasma antibodies reactive to neuronal…”
BackgroundCytogenetic abnormalities and fragile-x syndrome in Autism Spectrum Disorder
Reddy, K. S. (2005) · BMC Medical Genetics · doi:10.1186/1471-2350-6-3 · Cited by 222 · see citing works
Gilmore, J. H., Jarskog, L. F., & Vadlamudi, S. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.10.008 · Cited by 177 · see citing works
Wills, S., Cabanlit, M., Bennett, J., Ashwood, P., Amaral, D. G., & Van de Water, J. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.07.007 · Cited by 163 · see citing works
Self-citationChromosomal abnormalities in a clinic sample of individuals with autistic disorder
Wassink, T. H., Piven, J., & Patil, S. R. (2001) · Psychiatric Genetics · doi:10.1097/00041444-200106000-00001 · Cited by 157 · see citing works
Flagged first, then by citations
Research works printed but not linked: 21
- Ashwood P Anthony A Pellicer AA Torrente F Walker-Smith JA Wakefield AJ Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology J Clin Immunol 2003 23 504 517 15031638
- Ashwood P Anthony A Torrente F Wakefield AJ Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10 J Clin Immunol 2004 24 664 673 15622451
- Cabanlit M W S Goines P Ashwood P Van de Water J Brain-specific Autoantibodies in the Plasma of Subjects with Autistic Spectrum Disorder Ann NY Acad Sci 2007 92 103 17804536
- Coffey SM C K Tartaglia N Tassone F Nguyen DV Pan R Bronsky HE Yuhas J Borodyanskaya M Grigsby J Doerflinger M Hagerman PJ Hagerman RJ Expanded clinical phenotype of women with the FMR1 premutation Am J Med Genet A 146A 2008 1009 1016 18348275 PMC2888464
- Connolly A Chez M Streif EM Keeling RM Golumbek PT Kwon JM Riviello JJ Robinson RG Neuman RJ Deuel RM Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy Biol Psychiatry 2006 59 354 363 16181614
- Enstrom A Van de Water JA Ashwood P Autoimmunity in autism Curr Opin Investig Drugs 2009 10 463 473 PMC6952169 19431079
- Estecio M Fett-Conte AC Varella-Garcia M Fridman C Silva AE Molecular and cytogenetic analyses on Brazilian youths with pervasive developmental disorders J Autism Dev Disord 2002 32 35 41 11916331
- Gadient R Patterson PH Leukemia inhibitory factor, Interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury Stem Cells 1999 17 127 137 10342555
- Gupta S Aggarwal S Rashanravan B Lee T Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism J Neuroimmunol 1998 85 106 109 9627004
- Hagerman R Altshul-Stark D McBogg P "Recurrent otitis media in boys with the fragile X syndrome American Journal of Diseases of Children 1987 141 184 187 3812386
- Hagerman RJ Hagerman PJ Fragile X Syndrome: Diagnosis, Treatment, and Research 2002 3rd Edition Baltimore The Johns Hopkins University Press
- Hagerman RJ Lessons from fragile X regarding neurobiology, autism, and neurodegeneration J Dev Behav Pediatr 2006 27 63 74 16511373
- Harris SW Hessl D Goodlin-Jones B Ferranti J Bacalman S Barbato I Tassone F Hagerman PJ Herman H Hagerman RJ Autism profiles of males with fragile X syndrome American Journal of Mental Retardation 2008 113 427 438 19127654 PMC2629645
- Heuer L Ashwood P Schauer J Goines P Krakowiak P Hertz-Picciotto I Hansen R Croen LA Pessah IN Van de Water JA Reduced Levels of Immunoglobulin in Children With Autism Correlates With Behavioral Symptoms Autism Research 2008 1 275 283 19343198 PMC2663897
- Irwin SA Galvez R Greenough WT Dendritic spine structural anomalies in fragile-X mental retardation syndrome Cerebral Cortex 2000 10 1038 1044 11007554
- Kaufmann WE Cortell R Kau AS Bukelis I Tierney E Gray RM Cox C Capone GT Stanard P Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors Am J Med Genet 129A 2004 225 234 15326621
- Mehler MF K J Cytokines in brain development and function Adv Protein Chem 1998 52 223 251 9917922
- Rogers SJ Wehner EA Hagerman RJ The behavioral phenotype in fragile X: Symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders J Dev Behav Pediatr 2001 22 409 417 11773805
- Singer HS M C Williams PN Yoon DY Hong JJ Zimmerman AW Antibrain antibodies in children with autism and their unaffected siblings J Neuroimmunol 2006 178 149 155 16842863
- Tassone F Pan R Amiri K Taylor AK Hagerman PJ A rapid polymerase chain reaction-based screening method for identification of all expanded alleles of the fragile X (FMR1) gene in newborn and high-risk populations J Mol Diagn 2008 10 43 49 18165273 PMC2175542
- Weiler IJ Greenough WT Synaptic synthesis of the Fragile X protein: possible involvement in synapse maturation and elimination American Journal of Medical Genetics 1999 83 248 252 10208156
Cited by
Sorted by citations
Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I., & Van de Water, J. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.08.003 · Cited by 940 · see citing works
Self-citationGaray, P. A., Hsiao, E. Y., Patterson, P. H., & McAllister, A. K. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.07.008 · Cited by 366 · see citing works
Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders
Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I. N., & Van de Water, J. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.10.025 · Cited by 279 · see citing works
Self-citationA Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk
Blair, D. R., Lyttle, C. S., Mortensen, J. M., Bearden, C. F., Jensen, A. B., Khiabanian, H., Melamed, R., Rabadan, R., Bernstam, E. V., Brunak, S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.030 · Cited by 215 · see citing works
FMR1 premutation and full mutation molecular mechanisms related to autism
Hagerman, R., Au, J., & Hagerman, P. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9084-5 · Cited by 85 · see citing works
Self-citationCareaga, M., Noyon, T., Basuta, K., Van de Water, J., Tassone, F., Hagerman, R. J., & Ashwood, P. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-110 · Cited by 20 · see citing works
Self-citationKong, S. W., Sahin, M., Collins, C. D., Wertz, M. H., Campbell, M. G., Leech, J. D., Krueger, D., Bear, M. F., Kunkel, L. M., & Kohane, I. S. (2014) · Molecular Autism · doi:10.1186/2040-2392-5-16 · Cited by 19 · see citing works
An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis
Talvio, K., Wagner, V. A., Minkeviciene, R., Kirkwood, J. S., Kulinich, A. O., Umemori, J., Bhatia, A., Hur, M., Käkelä, R., Ethell, I. M., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-05147-9 · Cited by 8 · see citing works
- Authors
- Ashwood, P., Nguyen, D. V., Hessl, D., Hagerman, R. J., & Tassone, F.
- Affiliations
- University of California, Davis (US)
- University of California Davis Medical Center (US)
- Corresponding author
- Tassone, Flora
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 24
- Issue
- 6
- Pages
- 898-902
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC3626458
- OpenAlex
- W2041513855
- Cited by
- 80
- References
- 8
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 1 · 2023: 5 · 2022: 6 · 2021: 1 · 2020: 10 · 2019: 5 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- M.I.N.D. Institute Pilot
- NIH (HD 036071, HD 02274, MH 77554)
- National Center for Research Resources (UL1 RR024146)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- fragile X syndrome, autism spectrum disorder, plasma cytokines, chemokines, immune dysregulation, interleukin-1 alpha, interleukin-6, RANTES, CXCL10, eotaxin, MCP-1, pathogenesis
- MeSH terms
- Adaptation, Psychological, Adolescent, Adult, Autistic Disorder, Blood Proteins, Child, Child, Preschool, Cognition, DNA, Fragile X Syndrome, Humans, Intelligence Tests, Male, Psychiatric Status Rating Scales, Biomarkers, Cytokines, Chemokines, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
