The DOI matches its Crossref record; 62 of the 64 references it cites were found in a registry or an index.
Increased IgG4 levels in children with autism disorder
Open accessAbstract
Accumulating evidence indicates that immune dysfunction is associated with autism disorders in a significant subset of children. Previous reports have shown abnormal immunoglobulin (Ig) levels, including an increased presence of autoreactive antibodies in the circulation of individuals with autism. As IgG is the predominant antibody isotype in circulation, we expected that an altered immune response could result in an abnormal IgG subclass profile in children with autism. We examined circulating plasma levels of IgG1, IgG2, IgG3, and IgG4 in 241 children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a large epidemiologic case-control investigation, including 114 children who meet full criteria for autism disorder (AU), 96 typically developing control children (TD) from a randomly selected sample of the general population, and 31 children with developmental delays (DD). We report significantly increased levels of the IgG4 subclass in children with AU compared with TD control children (p=0.016) and compared with DD controls (p=0.041). These results may suggest an underlying immunological abnormality in AU subjects resulting in elevated IgG4 production. Further investigation is necessary to elucidate the relationship between immunological findings and behavioral impairments in autism.
Overview
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
Verification
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?
In the citing paper
“Elevated plasma cytokine levels (IL-1β, IL-6, IL-12p40 and TNFα) [82–84], altered immunoglobulin levels [85, 86], elevated levels of complement proteins [87], and increased chemokine levels (CCL2, CCL5 and CCL11) [88] are reported in the plasma of young children with AD compared with matched typically developing children.”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [86]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520 · cited 15×
“Based on age and skill level, 92 AU participants were administered ADOS module 1, designed for the least verbal children.”
InfluentialMullen Scales of Early Learning
Bradley‐Johnson, S. (1997) · Psychology in the Schools · doi:10.1002/(sici)1520-6807(199710)34:4 · Cited by 2,329
Prevalence of Autism in a US Metropolitan Area
Yeargin-Allsopp, M., Rice, C., Karapurkar, T., Doernberg, N., Boyle, C., & Murphy, C. (2003) · JAMA · doi:10.1001/jama.289.1.49 · Cited by 1,248 · cited 2×
“Autism spectrum disorders are a group of relatively common pervasive neurodevelopmental disorders affecting between 2 and 6 children per 1000 (Chakrabarti and Fombonne, 2005; Fombonne, 2005; Yeargin-Allsopp et al., 2003).”
Maternal 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 · cited 2×
“…postnatal infections have also been associated with autism (Ashwood et al., 2006; Fortier et al., 2007; Meyer et al., 2006; Miyazaki et al., 2005; Narita et al., 2002; Niehus and Lord, 2006; Rodier et al., 1997; Rosen et al., 2007; Shi et al., 2003; Vojdani et al., 2003; Williams et al., 2001).”
Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange
Kolfschoten, M. V. D. N., Schuurman, J., Losen, M. H., Bleeker, W. K., Martínez‐Martínez, P., Vermeulen, E., den Bleker, T. H., Wiegman, L., Vink, T., Aarden, L. A., et al. (2007) · Science · doi:10.1126/science.1144603 · Cited by 981 · cited 1×
“These features drastically alter the biological function of the IgG4 antibody, shifting its function to that of a blocking or inhibiting antibody rather than one of protection through the more conventional routes, such as complement fixation (van der Neut Kolfschoten et al., 2007).”
Pervasive Developmental Disorders in Preschool Children: Confirmation of High Prevalence
Chakrabarti, S., & Fombonne, E. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.6.1133 · Cited by 791 · cited 2×
“Autism spectrum disorders are a group of relatively common pervasive neurodevelopmental disorders affecting between 2 and 6 children per 1000 (Chakrabarti and Fombonne, 2005; Fombonne, 2005; Yeargin-Allsopp et al., 2003).”
Butler, M. G., Dasouki, M. J., Zhou, X.-P., Talebizadeh, Z., Brown, M., Takahashi, T. N., Miles, J. H., Wang, C. H., Stratton, R., Pilarski, R., et al. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2004.024646 · Cited by 778 · cited 2×
“(Beilmann et al., 1997; Butler et al., 2005; Garbett et al., 2008; Pardo and Eberhart, 2007; Skaar et al., 2005).”
(2005) · PubMed · Cited by 775
Meyer, U., Nyffeler, M., Engler, A., Urwyler, A., Schedlowski, M., Knuesel, I., Yee, B. K., & Feldon, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-06.2006 · Cited by 774 · cited 2×
“Environmental triggers, such as thalidomide, valproic acid, and prenatal and early postnatal infections have also been associated with autism (Ashwood et al., 2006; Fortier et al., 2007; Meyer et al., 2006; Miyazaki et al., 2005; Narita et al., 2002; Niehus and Lord, 2006; Rodier et al., 1997; Rosen et al., 2007; Shi…”
Aalberse, R. C., van der Gaag, R., & van Leeuwen, J. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.130.2.722 · Cited by 740 · cited 3×
“Increased IgG4 is found in patients with atopy as well as prolonged chronic antigen stimulation (Aalberse et al., 1983; Shakib, 1986).”
Flagged first, then by citations
2 of the 64 references couldn’t be matched to a known paper.
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
“…have described links between genes that encode for immune-related proteins and ASD, suggesting that abnormalities in the immune system may influence aspects of brain development and synaptic functions that negatively impact clinical outcomes relevant to ASD (reviewed in Enstrom et al., 2009a).”
BackgroundSelf-citationConsensus 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
“Elevated plasma cytokine levels (IL-1β, IL-6, IL-12p40, and TNFα) [82–84], altered immunoglobulin levels [85, 86], elevated levels of complement proteins [87], and increased chemokine levels (CCL2, CCL5, and CCL11) [88] are reported in the plasma of young children with AD compared with matched typically developing chi…”
BackgroundSelf-citationTraffic-Related Air Pollution, Particulate Matter, and Autism
Volk, H. E., Lurmann, F., Penfold, B., Hertz-Picciotto, I., & McConnell, R. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.266 · Cited by 638
Self-citationThe role of immune dysfunction in the pathophysiology of autism
Onore, C., Careaga, M., & Ashwood, P. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.08.007 · Cited by 635
Self-citationEmerging Roles for the Gut Microbiome in Autism Spectrum Disorder
Vuong, H. E., & Hsiao, E. Y. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.08.024 · Cited by 595
The Role of the Immune System in Autism Spectrum Disorder
Meltzer, A., & Van de Water, J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.158 · Cited by 533
Residential Proximity to Freeways and Autism in the CHARGE Study
Volk, H. E., Hertz-Picciotto, I., Delwiche, L., Lurmann, F., & McConnell, R. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1002835 · Cited by 347
Self-citationDifferential monocyte responses to TLR ligands in children with autism spectrum disorders
Enstrom, A. M., Onore, C. E., Van de Water, J. A., & Ashwood, P. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.08.001 · Cited by 294
“The CHARGE study patient diagnostic criteria have previously been discussed in detail (Enstrom et al., 2009a; Hertz-Picciotto et al., 2006).”
Self-citationAltered T cell responses in children with autism
Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I. N., & Van de Water, J. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.09.002 · Cited by 281
Self-citationAssociations 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
“…of cytokines by peripheral bloodmononuclear cell (PBMC) cultures (Ashwood et al., 2008, 2009, 2010, in press-a,b; Ashwood and Wakefield, 2006; Enstrom et al., 2009a; Enstrom et al., 2010; Jyonouchi et al., 2001; Molloy et al., 2005; Onore et al., 2009; Vargas et al., 2005; Zimmerman et al.,…”
BackgroundMethodResultInfluentialSelf-citationJones, K. L., Croen, L. A., Yoshida, C. K., Heuer, L., Hansen, R., Zerbo, O., DeLorenze, G. N., Kharrazi, M., Yolken, R., Ashwood, P., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.77 · Cited by 260
Self-citationThe Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder
Masi, A., Glozier, N., Dale, R. C., & Guastella, A. J. (2017) · Neuroscience Bulletin · doi:10.1007/s12264-017-0103-8 · Cited by 274
“Increased levels of the IgG4 subclass have been identified in children with ASD [76].”
BackgroundThe Immune System’s Role in the Biology of Autism
Goines, P. E., & van de Water, J. A. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283373514 · Cited by 241
Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders
Hughes, H. K., Ko, E. M., Rose, D. R., & Ashwood, P. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00405 · Cited by 253
Self-citationThe Potential Role of Probiotics in the Management of Childhood Autism Spectrum Disorders
Critchfield, J. W., van Hemert, S., Ash, M. E., Mulder, L. H. C., & Ashwood, P. (2011) · Gastroenterology Research and Practice · doi:10.1155/2011/161358 · Cited by 178
“These findings include an abnormal ratio of CD4+ to CD8+ T-cells, abnormal or skewed T-helper-cell (TH1/TH2/TH17) cytokine profiles, elevated blood monocyte counts, decreased lymphocyte numbers, self-reactive antibodies to brain and CNS proteins, neuroinflammation, imbalance of serum and mucosal immunoglobulin levels…”
BackgroundSelf-citationEvidence supporting an altered immune response in ASD
Mead, J., & Ashwood, P. (2015) · Immunology Letters · doi:10.1016/j.imlet.2014.11.006 · Cited by 165
Self-citationJung, C., Lin, Y.-T., & Hwang, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075510 · Cited by 170
“Oxidative stress may contribute to the pathogenesis of ASD through lipid peroxidation, reduced antioxidant activity, elevated nitric oxide level [18–23] and inflammation [24,25].”
BackgroundThe Impact of Neuroimmune Alterations in Autism Spectrum Disorder
Gottfried, C., Bambini-Junior, V., Francis, F., Riesgo, R., & Savino, W. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00121 · Cited by 143
“Increased plasma levels of IgG4 in children with ASD were also observed (151).”
BackgroundIn Search of Cellular Immunophenotypes in the Blood of Children with Autism
Ashwood, P., Corbett, B. A., Kantor, A. B., Schulman, H., de Water, J. V., & Amaral, D. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019299 · Cited by 151
“Impairments in social behaviors, for example, are associated with decreased levels of TGFb1 [50], increased IL-1b and IL-13 [12], increased macrophage inhibitory factor [54], decreased platelet-endothelial adhesion molecule [55], total IgG [27], increased IgG4 isotype [26], altered T cell responses [8], chemokine leve…”
BackgroundSelf-citationAutoantibodies to cerebellum in children with autism associate with behavior
Goines, P., Haapanen, L., Boyce, R., Duncanson, P., Braunschweig, D., Delwiche, L., Hansen, R., Hertz-Picciotto, I., Ashwood, P., & Van de Water, J. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.11.017 · Cited by 134
Self-citationMast cell activation and autism
Theoharides, T. C., Angelidou, A., Alysandratos, K.-D., Zhang, B., Asadi, S., Francis, K., Toniato, E., & Kalogeromitros, D. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.017 · Cited by 125
Immune Abnormalities in Autism Spectrum Disorder—Could They Hold Promise for Causative Treatment?
Gładysz, D., Krzywdzińska, A., & Hozyasz, K. K. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0822-x · Cited by 134
“ASD children in comparison to typically developing controls and children with non-autistic developmental delay were confirmed in another study [109].”
ResultZerbo, O., Yoshida, C. K., Grether, J. K., de Water, J. V., Ashwood, P., DeLorenze, G. N., Hansen, R. L., Kharrazi, M., & Croen, L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-113 · Cited by 116
“Several research groups have found that individuals with ASD have increased neuroinflammation in brain tissues [10-12], imbalances in immunoglobulins, including increased levels of plasma IgG4 [13], reduced levels of total IgG [14] or reduced levels of IgG and IgM [15,16], and imbalances in cytokine/chemokine levels […”
BackgroundSelf-citationThe Neurobiology of Lipid Metabolism in Autism Spectrum Disorders
Tamiji, J., & Crawford, D. A. (2010) · Neurosignals · doi:10.1159/000323189 · Cited by 116
Air pollution and autism in Denmark
Ritz, B. R., Liew, Z., Yan, Q. J., Cuia, X., Virk, J., Ketzel, M., & Raaschou‐Nielsen, O. (2018) · Environmental Epidemiology · doi:10.1097/ee9.0000000000000028 · Cited by 103
Genome-wide expression studies in Autism spectrum disorder, Rett syndrome, and Down syndrome
Lintas, C., Sacco, R., & Persico, A. M. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.11.010 · Cited by 96
Frye, R. E., & Rossignol, D. A. (2016) · Clinical Medicine Insights Pediatrics · doi:10.4137/cmped.s38337 · Cited by 96
Dickerson, A. S., Rahbar, M. H., Han, I., Bakian, A. V., Bilder, D. A., Harrington, R. A., Pettygrove, S. D., Durkin, M. S., Kirby, R. S., Wingate, M. S., et al. (2015) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2015.07.024 · Cited by 93
“Studies have also shown that inflammationmay contribute to the pathogenesis of ASD (Enstrom et al., 2009; Li et al., 2009).”
BackgroundPlasma cytokine levels in children with autistic disorder and unrelated siblings
Manzardo, A. M., Henkhaus, R. S., Dhillon, S., & Butler, M. G. (2011) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2011.12.003 · Cited by 84
Dickerson, A. S., Rahbar, M. H., Bakian, A. V., Bilder, D. A., Harrington, R. A., Pettygrove, S. D., Kirby, R. S., Durkin, M. S., Han, I., Moyé, L. A., et al. (2016) · Environmental Monitoring and Assessment · doi:10.1007/s10661-016-5405-1 · Cited by 85
“2003), and arsenic (Jarup 2003) being neurotoxicants that frequently cross the blood-brain barrier affecting neurodevelopment, inflammation from exposure to air pollutants may also contribute to risk of ASD through adverse effects on neurodevelopment (Block & Calderon-Garciduenas 2009; Calderon-Garciduenas et al. 2009…”
BackgroundImmune allergic response in Asperger syndrome
Magalhães, E. S. D. S., Mariz, F. P., Bastos-Pinto, S., Pontes, A. T., Prado, E. A., & deAzevedo, L. C. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.09.015 · Cited by 69
Similarities in features of autism and asthma and a possible link to acetaminophen use
Becker, K. G., & Schultz, S. T. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.08.033 · Cited by 69
“Altered levels of immunoglobulins [1–3], cytokines [4] and, inflammatory”
BackgroundDecreased cellular IL-23 but not IL-17 production in children with autism spectrum disorders
Onore, C. E., Enstrom, A. M., Krakowiak, P., Hertz‐Picciotto, I., Hansen, R., de Water, J. V., & Ashwood, P. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.09.005 · Cited by 69
“…(TGF-β1) (Ashwood et al., 2008), macrophage inhibitory factor (Grigorenko et al., 2008), P-selectin (Iwata et al., 2008) immunoglobulin-G4 (Enstrom et al., 2009b), and monocyte activation (Enstrom et al., 2009c) and may suggest that dysfunctional immune responses and/or activity may…”
Self-citationOnore, C. E., Nordahl, C. W., Young, G. S., de Water, J. V., Rogers, S. J., & Ashwood, P. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.05.004 · Cited by 63
Self-citationSavino, R., Carotenuto, M., Polito, A. N., Noia, S. D., Albenzio, M., Scarinci, A., Ambrosi, A., Sessa, F., Tartaglia, N., & Messina, G. (2020) · Brain Sciences · doi:10.3390/brainsci10090631 · Cited by 53
“Additional immune alterations have been described in ASD individuals including imbalances in antibody levels [46,47], higher neural autoantibodies and pro-inflammatory levels [36], abnormalities in the ratio of Th1/Th2/Th17 cells [48], and reduced natural killer (NK) cell activity [49].”
BackgroundModeling autism: a systems biology approach
Randolph-Gips, M. M., & Srinivasan, P. N. (2012) · Journal of Clinical Bioinformatics · doi:10.1186/2043-9113-2-17 · Cited by 49
“Multiple studies have found a correlation between abnormal levels of immune factors and core autistic deficits such as speech, mood and social deficits [79-84].”
BackgroundCortelazzo, A., Felice, C. D., Guerranti, R., Signorini, C., Leoncini, S., Zollo, G., Leoncini, R., Timperio, A. M., Zolla, L., Ciccoli, L., et al. (2016) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201500076 · Cited by 46
“Environmental triggers could be also associated with the increased immunoglobulins levels observed in our examined autistic cohort, and this evidence is in line with earlier reports on immune dysfunction in autism [36, 37].”
Wasilewska, J., Kaczmarski, M. G., Stasiak‐Barmuta, A., Tobolczyk, J., & Kowalewska, E. (2012) · Archives of Medical Science · doi:10.5114/aoms.2012.28561 · Cited by 45
“found increased IgG due to a rise in specific IgG subclasses IgG2 and IgG4 in subjects with autism [35, 36].”
BackgroundIncreased Anti-Phospholipid Antibodies in Autism Spectrum Disorders
Careaga, M., Hansen, R. L., Hertz-Piccotto, I., de Water, J. V., & Ashwood, P. (2013) · Mediators of Inflammation · doi:10.1155/2013/935608 · Cited by 44
Self-citationThe maternal autoimmune environment affects the social behavior of offspring
Zhang, Y., Gao, D., Kluetzman, K., Mendoza, A., Bolivar, V. J., Reilly, A. A., Kasten‐Jolly, J., & Lawrence, D. A. (2013) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2013.02.019 · Cited by 42
“Most studies indicate serum IgG levels are increased in ASD, though decreased serum IgG also has been reported (Croonenberghs et al., 2002; Heuer et al., 2008; Enstrom et al., 2009a, 2009b).”
BackgroundMorales‐Suárez‐Varela, M., Peraita‐Costa, I., & González, A. L. (2016) · Environmental Research · doi:10.1016/j.envres.2016.11.022 · Cited by 45
“…to the pathogenesis of ASD through lipid peroxidation, reduced antioxidant activity, elevated nitric oxide level and inflammation (James et al., 2009; Chauhan et al., 2004; Ming et al., 2005; Zoroğlu et al., 2004; Yorbik et al., 2002; Söğüt et al., 2003; Enstrom et al., 2009; Li et al., 2009).”
BackgroundTorres, A. R., Westover, J. B., Gibbons, C., Johnson, R. C., & Ward, D. C. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.07.014 · Cited by 41
“…et al., 2011), altered cytokine levels (Molloy et al., 2006; Ashwood et al., 2011), changes in lymphocyte subsets (Furlano et al., 2001), a family history of autoimmune diseases (Atladóttir et al., 2009), and reduced natural killer (NK) cell activity (Warren et al., 1987; Enstrom et al., 2009a).”
BackgroundInfluentialAutism Spectrum Disorders: From Immunity to Behavior
Careaga, M., & Ashwood, P. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-62703-071-7_12 · Cited by 38
Self-citationNeonatally measured immunoglobulins and risk of autism
Grether, J. K., Croen, L., Anderson, M., Nelson, K. B., & Yolken, R. H. (2010) · Autism Research · doi:10.1002/aur.160 · Cited by 39
Li, H., Liu, H., Chen, X., Zhang, J., Tong, G., & Sun, Y. (2020) · European Journal of Pediatrics · doi:10.1007/s00431-020-03826-x · Cited by 37
T cell populations in children with autism spectrum disorder and co-morbid gastrointestinal symptoms
Rose, D. R., Yang, H. T., Careaga, M., Angkustsiri, K., de Water, J. V., & Ashwood, P. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100042 · Cited by 39
Self-citationC57BL/6J bone marrow transplant increases sociability in BTBR T+ Itpr3tf/J mice
Schwartzer, J. J., Onore, C. E., Rose, D. R., & Ashwood, P. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.05.019 · Cited by 34
“, 2005), increased peripheral immune cell activation (Ashwood et al., 2011a; Careaga et al., 2015a; Enstrom et al., 2009; Enstrom et al., 2010), elevated plasma pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8 and IL-12p40 (Ashwood et al.”
BackgroundSelf-citationRossignol, D. A., & Frye, R. E. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11060488 · Cited by 35
“Significant improvements on Children’s Communication Checklist–2 speech and semantics as well as Autism Diagnostic Observation Schedule (ADOS) stereotyped behaviors and restricted interest, communication plus social interaction total, and reciprocal social interaction were found.”
BackgroundMethodTakyi, E., Nirmalkar, K., Adams, J. B., & Krajmalnik‐Brown, R. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2499580 · Cited by 37
“118 A meta-analysis by Morton et al. showed that bacteria, such as Bacteroides thetaio-taomicron , abundance was correlated with lower transforming growth factor beta (TGF-β) levels.”
Zhu, Z., Tang, S., Deng, X., & Wang, Y. (2020) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-020-04400-y · Cited by 31
Theoharides, T. C. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11090860 · Cited by 29
Neurodevelopmental toxicity induced by airborne particulate matter
Shang, M., Tang, M. X., & Xue, Y. (2022) · Journal of Applied Toxicology · doi:10.1002/jat.4382 · Cited by 30
“Several studies have shown that children with ASD have increased plasma pro-inflammatory cytokine levels and decreased tumor growth factor-β concentrations compared to healthy controls (Enstrom et al., 2009; Li et al., 2009).”
BackgroundHeuer, L. S., Rose, M., Ashwood, P., & Van de Water, J. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.07.001 · Cited by 28
“…of the same population of children reported an increase in IgG4, a subclass of IgG, but no change in the remaining subclasses IgG1, IgG2, and IgG3 using a different method of detection (Enstrom et al., 2009), adding to the uncertainty of immunoglobulin production as a predictor of autism risk.”
MethodInfluentialSelf-citationIdentification of autoimmune gene signatures in autism
Jung, J.-Y., Kohane, I. S., & Wall, D. P. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.62 · Cited by 24
Sun, C., Cheng, Y., Chen, I.-W., Chiu, H., Chung, W., Tzang, R., Fan, H.-Y., Lee, C., & Hung, K. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.1052806 · Cited by 28
“A clinical correlation between immune mediators and fetal neurodevelopment was further reflected by the finding that the increased level of serum immunoglobulin G (IgG) in women diagnosed with autoimmune diseases (41) could access the fetal compartment during gestation (42) with a higher concentration being found in t…”
BackgroundLyall, K., Ames, J., Pearl, M., Traglia, M., Weiss, L. A., Windham, G. C., Kharrazi, M., Yoshida, C. K., Yolken, R. H., Volk, H. E., et al. (2021) · Molecular Autism · doi:10.1186/s13229-021-00429-7 · Cited by 25
Self-citationProfiling for novel proteomics biomarkers in neurodevelopmental disorders
Dudley, E., Häßler, F., & Thome, J. (2011) · Expert Review of Proteomics · doi:10.1586/epr.10.97 · Cited by 21
Shen, C., Zhao, X.-L., Ju, W., Zou, X.-B., Huo, L.-R., Yan, W., Zou, J.-H., Yan, G.-D., Jenkins, E. C., Brown, W. T., et al. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9463-5 · Cited by 18
“Autistic children could show abnormal immune responses and have elevated serum immunoglobulin E (IgE) and/or other Ig abnormalities (Magalhães et al. 2009; Bakkaloglu et al. 2008; Cohly and Panja 2005; Molloy et al. 2006; Singer et al. 2006; Enstrom et al. 2009), which may provide a clue for treatment (Careaga et al.”
BackgroundMakris, G., Chouliaras, G. L., Apostolakou, F., Papageorgiou, C., Chrousos, G. P., Papassotiriou, I., & Pervanidou, P. (2021) · Children · doi:10.3390/children8060478 · Cited by 18
“Several studies have shown peripheral immune abnormalities in patients with ASD, including abnormal or skewed T helper cell cytokine profiles [3], an imbalance of serum immunoglobulin levels [7], NK cell activation [8], increased monocyte responses [9],”
BackgroundChiu, H., Sun, C., Tsai, S., Bai, Y., Hung, K., Hsu, J.-W., Huang, K., Su, T., Chen, T., Sun, A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-08834-5 · Cited by 19
Saxena, V., Ramdas, S., Ochoa, C. R., Wallace, D. R., Bhide, P. G., & Kohane, I. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048835 · Cited by 20
“Peripheral blood transcriptional profiling in autistic children (not suffering from other disorders such as fragile X mental retardation) showed increased expression of Natural killer cell receptors and effector molecules [22].”
BackgroundAhmad, S. F., Nadeem, A., Ansari, M. A., Bakheet, S. A., AL-Ayadhi, L. Y., & Attia, S. M. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.04.011 · Cited by 17
“Additionally, there have been several reports of dysregulated peripheral T cell activation, changes in lymphocyte subsets, and an imbalance in immunoglobulin levels (Enstrom et al., 2009; Wills et al., 2009).”
The association between particulate matter 2.5 exposure and children with autism spectrum disorder
Geng, R., Fang, S., & Li, G. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.05.003 · Cited by 17
“In addition, traffic-related air pollution induced systemic inflammation and oxidative stress after both short- and long-term exposure, processes that mediate the effects of air pollution on the pathogenesis of autism (Enstrom et al., 2009; James et al., 2009).”
BackgroundThe need for a comprehensive molecular characterization of autism spectrum disorders
Broek, J. A. C., Brombacher, E., Stelzhammer, V., Guest, P. C., Rahmoune, H., & Bahn, S. (2013) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114571300117x · Cited by 17
“, 2009) IgG3 1 , 0 , 4↔ Serum, plasma 4 (5 projects) (Trajkovski et al., 2004; Enstrom et al., 2009; Spiroski et al., 2009) IgG4 3 , 0 , 1↔ Serum, plasma 4 (Trajkovski et al.”
InfluentialMaternal elevated salt consumption and the development of autism spectrum disorder in the offspring
Afroz, K. F., & Alviña, K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1666-2 · Cited by 16
Angkustsiri, K., & Hansen, R. L. (2012) · Springer eBooks · doi:10.1007/978-3-642-02202-9_47 · Cited by 16
Self-citationSavino, R., Carotenuto, M., Polito, A. N., Di Noia, S., Albenzio, M., Scarinci, A., Ambrosi, A., Sessa, F., Tartaglia, N., & Messina, G. (2020) · doi:10.20944/preprints202007.0425.v1 · Cited by 54
[Research advances in immunological dysfunction in children with autism spectrum disorders].
Wang, T., Du, L., Shan, L., & Jia, F. (2014) · PubMed · Cited by 11
BrainGENIE: The Brain Gene Expression and Network Imputation Engine
Hess, J., Quinn, T. P., Zhang, C., Hearn, G. C., Chen, S., Beveridge, N. J., Carr, V. J., de Jong, S., Gardiner, E. J., Kelly, B. J., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02390-w · Cited by 10
Developmental exposure to mercury chloride does not impair social behavior of C57BL/6 × BTBR F1mice
Zhang, Y., Bolivar, V. J., & Lawrence, D. A. (2012) · Journal of Immunotoxicology · doi:10.3109/1547691x.2012.682663 · Cited by 11
Tsai, P.-H., Chen, M.-H., Su, T., Chen, Y. S., Hsu, J.-W., Huang, K.-L., Chang, W.-H., Chen, T., & Bai, Y. (2014) · Research in Autism · doi:10.1016/j.rasd.2013.12.022 · Cited by 9
Helminth therapy for autism under gut-brain axis- hypothesis
Arroyo-López, C. (2019) · Medical Hypotheses · doi:10.1016/j.mehy.2019.02.042 · Cited by 6
“In addition, Natural Killer T- cells have been largely implicated to autism presenting less responsive to cytokines [48,132].”
BackgroundAdvances in Causes and Treatment of Autism
XiaoLi, W. U., Jin, F., & Duan, Y. (2015) · Scientia Sinica Vitae · doi:10.1360/n052015-0108 · Cited by 5
Akintunde, M. E., Lin, Y., Krakowiak, P., Pessah, I. N., Hertz‐Picciotto, I., Puschner, B., Ashwood, P., & de Water, J. V. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100697 · Cited by 5
“…decreased natural killer cell lytic activity, abnormal cytokine and immunoglobulin levels, decreased peripheral lymphocyte numbers, as well as the presence of autoantibodies to brain proteins (Ashwood et al., 2011b; Enstrom et al., 2008, 2010b; Goines et al., 2011a; Heuer et al., 2008, 2012).”
BackgroundSelf-citationHumoral immunity and autism spectrum disorders
Fluegge, K. (2017) · Immunology Letters · doi:10.1016/j.imlet.2017.03.003 · Cited by 5
Prevalence of neurological diseases among patients with selective IgA deficiency
Magen, E., Geishin, A., Merzon, E., Green, I., Golan‐Cohen, A., Vinker, S., & Israel, A. (2023) · Allergy and Asthma Proceedings · doi:10.2500/aap.2023.44.230036 · Cited by 4
Jin, F., Duan, Y., & XiaoLi, W. U. (2015) · Chinese Science Bulletin (Chinese Version) · doi:10.1360/n972015-00355 · Cited by 3
Bhat, S. S., Kalal, B. S., Veena, K. M., Kakunje, A., Sahana, K. S. R., Rekha, P. D., Chandra, J., & Nasreen, I. (2021) · PubMed Central · Cited by 4
Gut–Brain Inflammation and Disrupted Homeostasis Due to Activation of Mast Cells and Microglia
Katiraei, P., Frye, R. E., & Theoharides, T. C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041768 · Cited by 3
“For instance, levels of serum IgG4, which are associated with food intolerance, increased in ASD [453,454].”
Sacco, R., Persico, A. M., Garbett, K. A., & Mirnics, K. (2010) · Advances in neurobiology · doi:10.1007/978-1-4419-7197-5_18 · Cited by 3
Immune Dysfunction in Autism Spectrum Disorders
Careaga, M., de Water, J. V., & Ashwood, P. (2012) · Molecular and integrative toxicology · doi:10.1007/978-1-61779-812-2_10 · Cited by 3
Self-citationImmune Abnormalities and Autism Spectrum Disorders
Akintude, M. E., Heuer, L. S., & de Water, J. V. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-391924-3.00016-8 · Cited by 3
Inscoe, J. R. (2010) · Cochlear Implants International · doi:10.1179/146701010x12726366068175 · Cited by 2
“In addition, recent evidence looking at the possible causes of autistic disorders concludes that ‘auto-immunity secondary to cCMV or Rubella infection may best explain autism in some children’ (Yamashita et al., 2003; Enstrom et al., 2009).”
BackgroundHypothesis: Conjugate vaccines may predispose children to autism spectrum disorders
Richmand, B. J. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.08.019 · Cited by 2
“However, the potential of conjugate vaccines to trigger ASDs needs to be carefully considered in light of the substantial body of evidence suggesting that neuroinflammatory and autoimmune processes may play a role in some cases of ASDs [19–26].”
BackgroundChildhood vaccination as a protective factor for developmental psychopathology
Kim, B., Ha, M., Kim, Y. S., Koh, Y., Kwon, H., Lim, M.-H., Paik, K.-C., Kim, H., Hong, P. S., & LEVENTHAL, B. L. (2020) · Research in Autism · doi:10.1016/j.rasd.2020.101653 · Cited by 2
Rose, D. R., & Ashwood, P. (2015) · Contemporary clinical neuroscience · doi:10.1007/978-1-4939-2190-4_6 · Cited by 2
Self-citationWawer, J., Chojęta, A., Wawer, G. A., Gładki, M. M., Klotzka, A., Kociński, B., Urbanowicz, T. K., Kocki, J., & Grywalska, E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26189242 · Cited by 1
“Other studies observed the shift in IgG subclass to IgG4 and suggested that children with autism are likely to have a higher percentage of circulating IgG with an inherently lower affinity for the antibody receptors on leukocytes [5,44].”
دراسة التأثير العكسي لتلوث الهواء على اضطرابات طيف التوحد لدى عينة من الأطفال العراقيين
الله, س. ع. ع., Al‐Garawi, Z. S., & العاصمي, ب. و. ع. ا. (2020) · مجلة العلوم الطبية و الصيدلانية · doi:10.26389/ajsrp.s110820 · Cited by 1
Music and Autism: New Ways of Research for Neuroscience
Salvo, M. D. (2024) · Springer eBooks · doi:10.1007/978-3-031-68338-1_14 · Cited by 1
Immune Dysfunction in Autism Spectrum Disorder
Malkova, N. V., & Hsiao, E. Y. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800109-7.00005-4 · Cited by 2
Metabolic Association Between the Gut–Brain Axis in Autism Spectrum Disorders
Delgado, M., Fochesato, A., Juncos, L., & Gargiulo, P. (2017) · Springer eBooks · doi:10.1007/978-3-319-53126-7_33 · Cited by 1
El-Ansary, A. K., Al-Dbass, A. M., & Qasem, H. (2018) · InTech eBooks · doi:10.5772/intechopen.69431 · Cited by 2
“inflammation in humans, which may contribute to the pathogenesis of autism [8, 9].”
BackgroundAutoimmune Disorder and Autism
Li, X., & Zou, H. (2011) · InTech eBooks · doi:10.5772/23020
“Other groups measured the plasma concentration of immunoglobulins and/or cytokines, autistic subjects exclusively exhibited abnormal immunoglobin and/or cytokine profiles [21-24].”
BackgroundAssociation of MIF with Autism Spectrum Disorders
Kawiková, I., Leckman, J. F., Morer, Á., & Grigorenko, E. L. (2012) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789814335362_0020
Gallagher, C. M. (2012) · SUNY Digital Repository Support (State University of New York System)
BrainGENIE : The Brain Gene Expression and Network Imputation EnginePreprint
Hess, J., Quinn, T. P., Zhang, C., Hearn, G. C., Chen, S., Kong, S. W., Cairns, M. J., Tsuang, M. T., Faraone, S. V., & Glatt, S. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.27.356766
“…, 2013; Padmos et al. , 2008; Savitz et al. , 2013; Tsuang et al. , 2005) ( k studies=6, n cases=84, n controls=101), and ASD (Tian et al. , 2011; Enstrom et al. , 2009; Stamova et al. , 2011; Hertz-Picciotto et al. , 2006; Glatt et al. , 2012; Kong et al. , 2012, 2013; Alter et al. , 2011) ( k…”
MethodThe Potential Role of Probiotics in theManagement of Childhood Autism SpectrumDisorders
Critchfield, J. W., van Hemert, S., Ash, M. E., & Ashwood, P. (2014)
Self-citationKohane, I. S. (2010) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.5459957.5423055
Bagasra, O., Heggen, C., & Hossain, M. I. (2018) · Wiley eBooks · doi:10.1002/9781119042280.ch9
Tsou, H.-L., Huang, Y., Chen, C., Kuo, S.-C., Tzeng, N., Lin, J., & Yeh, Y. (2022) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2022.103111
Metadata
- Authors
- Enstrom, A., Krakowiak, P., Onore, C., Pessah, I. N., Hertz-Picciotto, I., Hansen, R. L., Van de Water, J. A., & Ashwood, P.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Ashwood, Paul
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 23
- Issue
- 3
- Pages
- 389-395
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC2696343
- OpenAlex
- W2042013685
- Cited by
- 101
- References
- 64
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 15
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Environmental Protection Agency
- Emch Foundation
- University of California, Davis
- National Institute of Environmental Health Sciences (R01ES015359, P01ES011269)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, IgG4, IgG subclasses, immune dysfunction, children, developmental delay, CHARGE study, autoantibodies
- MeSH terms
- Analysis of Variance, Autistic Disorder, Developmental Disabilities, Child, Preschool, Female, Humans, Immunoglobulin G, Male, Case-Control Studies
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
