The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Elevation of Tumor Necrosis Factor-Alpha in Cerebrospinal Fluid of Autistic Children
Abstract
Recent reports implicating elevated cytokines in the central nervous system in a small number of patients studied with autism have reported clinical regression. These studies have not focused on tumor necrosis factor-alpha as a possible marker for inflammatory damage. A series of 10 children with autism had clinical evaluation of their serum and spinal fluid for inflammatory changes and possible metabolic disease as part of their neurological evaluation. Elevation of cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in all of the patients studied. The ratio of the cerebrospinal fluid levels to serum levels averaged 53.7:1. This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured. This observation may offer a unique insight into central nervous system inflammatory mechanisms that may contribute to the onset of autism and may serve as a potential clinical marker. More controlled study of this potentially important observation may prove valuable.
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In the citing paper
“Moreover, increases in many cytokines and chemokines are observed in the brain and cerebrospinal fluid (CSF) of individuals with AD, in particular; interleukin (IL)-6, transforming growth factor beta 1 (TGFβ1), C-C motif ligand 2 (CCL2) and CCL17 in the cerebellum [73–76].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [74]
In the citing paper
“Furthermore, evidence suggests that children with ASD have elevated levels of pro-inflammatory cytokines including, interleukin 6 (IL–6), tumour necrosis factor alpha (TNF–α), and interferon gamma (IFN-γ) in different tissues [3,4,5,6,7].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [5]
In the citing paper
“Similarly, IFN-γ has been noted as increased in individuals with ASD,13, 16, 17, 61 and IFN-γ was increased in ASD and correlated with C disporicum and C tertium.”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [17]
In the citing paper
“Furthermore, increased IL6 has been seen in clinical cohorts of ASD.13, 14, 17, 60”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [17]
Citations
Cites
(1943) · The Nervous child · Cited by 8,870
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
Proinflammatory Cytokines and Early Neurological Worsening in Ischemic Stroke
Vila, N., Castillo, J., Dávalos, A., & Chamorro, Á. (2000) · Stroke · doi:10.1161/01.str.31.10.2325 · Cited by 676
Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation
Nelson, K. B., Grether, J. K., Croen, L., Dambrosia, J. M., Dickens, B. F., Jelliffe‐Pawlowski, L. L., Hansen, R. L., & Phillips, T. M. (2001) · Annals of Neurology · doi:10.1002/ana.1024 · Cited by 434
Actions of TNF‐α on glutamatergic synaptic transmission in the central nervous system
Pickering, M., Cumiskey, D., & O'Connor, J. J. (2005) · Experimental Physiology · doi:10.1113/expphysiol.2005.030734 · Cited by 421
Cerebrospinal Fluid and Serum Markers of Inflammation in Autism
Zimmerman, A. W., Jyonouchi, H., Comi, A. M., Connors, S. L., Milstien, S., Varsou, A., & Heyes, M. P. (2005) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2005.03.014 · Cited by 300
Antibodies to Myelin Basic Protein in Children with Autistic Behavior
Singh, V. K., Warren, R. P., Odell, J. D., Warren, W. L., & Cole, P. (1993) · Brain, Behavior, and Immunity · doi:10.1006/brbi.1993.1010 · Cited by 274
Connolly, A. M., Chez, M. G., Streif, E. M., Keeling, R. M., Golumbek, P. T., Kwon, J. M., Riviello, J. J., Robinson, R., Neuman, R. J., & Deuel, R. K. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.07.004 · Cited by 265
Self-citationSerum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders
Connolly, A. M., Chez, M. G., Pestronk, A., Arnold, S. T., Mehta, S., & Deuel, R. K. (1999) · The Journal of Pediatrics · doi:10.1016/s0022-3476(99)70248-9 · Cited by 236
Self-citationShiozaki, T., Hayakata, T., Tasaki, O., Hosotubo, H., Fuijita, K., Mouri, T., Tajima, G., Kajino, K., Nakae, H., Tanaka, H., et al. (2005) · Shock · doi:10.1097/01.shk.0000161385.62758.24 · Cited by 152
Cited by
Sorted by citations
Maternal immune activation and abnormal brain development across CNS disorders
Knuesel, I., Chicha, L., Britschgi, M., Schobel, S. A., Bodmer, M., Hellings, J. A., Toovey, S., & Prinssen, E. P. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.187 · Cited by 880
Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis
Rossignol, D. A., & Frye, R. E. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.136 · Cited by 940
Elevated immune response in the brain of autistic patients
Li, X., Chauhan, A., Sheikh, A. M., Patil, S., Chauhan, V., Li, X.-M., Ji, L., Brown, T., & Malik, M. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.12.002 · Cited by 786
“…reports suggest that a combination of environmental or perhaps in utero risk factors, autoimmune risk factors and localized inflammation of the central nervous system may contribute to the pathogenesis of ASD (Nelson et al., 2001; Vargas et al., 2005; Zimmerman et al., 2005; Chez et al., 2007).”
BackgroundImmune involvement in schizophrenia and autism: Etiology, pathology and animal models
Patterson, P. H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.12.016 · Cited by 766
“Most important is the recent evidence of dysregulation of immune-related genes in the schizophrenic brain, and striking microglial and astrocyte activation as well as cytokine up-regulation in the autistic brain and CSF [7] [8] [9] [10] [11] [12] [13].”
Consensus Paper: Pathological Role of the Cerebellum in Autism
Fatemi, S. H., Aldinger, K. A., Ashwood, P., Bauman, M. L., Blaha, C. D., Blatt, G. J., Chauhan, A., Chauhan, V., Dager, S. R., Dickson, P. E., et al. (2012) · The Cerebellum · doi:10.1007/s12311-012-0355-9 · Cited by 723
Metadata
- Authors
- Chez, M. G., Dowling, T., Patel, P. B., Khanna, P., & Kominsky, M.
- Affiliations
- Sutter Health (US)
- Illinois State University (US)
- Rosalind Franklin University of Medicine and Science (US)
- Corresponding author
- Chez, Michael G.
- ORCID
- Chez, Michael G.
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 36
- Issue
- 6
- Pages
- 361-365
- ISSN
- 0887-8994 (ISSN-L)
- OpenAlex
- W2063547860
- Cited by
- 317
- References
- 16
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 20 · 2023: 10 · 2022: 21 · 2021: 22 · 2020: 19 · 2019: 16 · 2018: 24 · 2017: 15 · 2016: 21 · 2015: 17 · 2014: 15 · 2013: 21 · 2012: 18
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TNF-α, cerebrospinal fluid, autism spectrum disorder, cytokines, neuroinflammation, biomarkers
- MeSH terms
- Autistic Disorder, Central Nervous System, Child, Child, Preschool, Encephalitis, Female, Humans, Infant, Male, Tumor Necrosis Factor-alpha, Biomarkers, Early Diagnosis
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