Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder
Open accessAbstract
Circulating 45 and 62kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N=355), their unaffected siblings (N=142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62kDa antibodies are correlated with autism severity: the 45kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62kDa autoAb in the child is significantly associated with presence of the 39 and/or 73kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering.
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Braunschweig et al. found that paired reactivity to the 37 and 73 kDa bands correlated with lower expressive language, and reactivity to a 39 kDa band and paired 39/73 kDa reactivity correlated with broader ASD diagnosis and increased irritability on the Aberrant Behavior Checklist.
“finding that paired brain reactivity (ie, to the 37 and 73 kDa bands) correlated with lower expressive language”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Piras et al, 2014
45 and 62 kDa antibodies in children correlated with autism severity, IQ, and impaired motor function and social interaction as scored on the Vineland Adaptive Behavior Scales.
“The authors showed that 45 and 62 kDa antibodies in the children correlated with severity of autism, IQ, and impaired motor function and social interaction, as scored on the Vineland Adaptive Behavior Scales.”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Piras et al, 2014
Maternal and child-borne autoantibodies each retain distinct and defining characteristics despite correlations between the two populations.
“showing that while correlations between the two discrete autoantibody populations do exist, maternal-and child-borne autoantibodies each retain their own distinct and defining characteristics.”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Piras et al, 2014
After birth and throughout childhood, an individual with ASD may have endogenous anti-brain autoantibodies, separate from maternal IgG, that correlate with aberrant behaviors and impaired development.
“After birth and at least throughout childhood, an individual with ASD may have endogenous anti-brain autoantibodies, separate from any maternal IgG, which correlate with aberrant behaviors and impaired development.”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Piras et al, 2014
In a cohort of 355 Italian children with autism and their mothers and unaffected siblings, autoantibodies in autistic individuals correlated with increased severity, stereotypies, and cognitive impairment.
“An examination of anti-brain autoantibodies in a cohort of 355 Italian children with autism and their mothers and unaffected siblings found that autoantibodies in autistic individuals correlated with increased severity, stereotypies, and cognitive impairment (Piras et al, 2014).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Piras et al, 2014
Although there is a correlation between maternal and patient autoantibodies, there appear to be at least some differences in effect.
“although there exists a correlation between the two there does appear to be at least some differences in effect (Piras et al, 2014).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Piras et al, 2014
Offending antibodies of either origin appear to persist systemically for extended periods.
“Offending antibodies of either origin appear to persist systemically for extended periods of time (Mostafa and Al-Ayadhi, 2012;Piras et al, 2014;Singer et al, 2006;Zimmerman et al, 2007)”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Piras et al, 2014
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Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
No adjustments are needed for multiple comparisons.
Rothman, K. J. (1990) · Epidemiology · doi:10.1097/00001648-199001000-00010 · Cited by 5,965 · see citing works
What's wrong with Bonferroni adjustments
Perneger, T. V. (1998) · BMJ · doi:10.1136/bmj.316.7139.1236 · Cited by 5,900 · see citing works
Adjusting for multiple testing—when and how?
Bender, R., & Lange, S. (2001) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(00)00314-0 · Cited by 3,060 · see citing works
Mapping early brain development in autism
Courchesne, E., Pierce, K., Schumann, C. M., Redcay, E., Buckwalter, J. A., Kennedy, D. P., & Morgan, J. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.016 · Cited by 860 · see citing works
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 · see citing works
Self-citationCorrection for Multiple Testing
Streiner, D. L., & Norman, G. R. (2011) · CHEST Journal · doi:10.1378/chest.11-0523 · Cited by 573 · 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
Y-box-binding protein 1 (YB-1) and its functions
Eliseeva, I. A., Kim, E. R., Guryanov, S. G., Ovchinnikov, L. P., & Lyabin, D. N. (2011) · Biochemistry (Moscow) · doi:10.1134/s0006297911130049 · Cited by 389 · see citing works
Autism: maternally derived antibodies specific for fetal brain proteins.
Braunschweig, D., Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R. L., Croen, L., Pessah, I., & van de Water, J. A. (2007) · Neurotoxicology · doi:10.1016/j.neuro.2007.10.010 · Cited by 281 · see citing works
Crosstalk between the circadian clock circuitry and the immune system
Cermakian, N., Lange, T., Golombek, D., Sarkar, D., Nakao, A., Shibata, S., & Mazzoccoli, G. (2013) · Chronobiology International · doi:10.3109/07420528.2013.782315 · Cited by 279 · see citing works
Autism-specific maternal autoantibodies recognize critical proteins in developing brain
Braunschweig, D., Krakowiak, P., Duncanson, P., Boyce, R., Hansen, R. L., Ashwood, P., Hertz-Picciotto, I., Pessah, I. N., & Van de Water, J. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.50 · Cited by 257 · see citing works
Self-citationMaternal neuronal antibodies associated with autism and a language disorder
Dalton, P., Deacon, R., Blamire, A., Pike, M., McKinlay, I., Stein, J., Styles, P., & Vincent, A. (2003) · Annals of Neurology · doi:10.1002/ana.10557 · Cited by 204 · cited 1× · see citing works
“These results largely replicate previous findings, whereby mAbs have been found associated with high rates of language regression and poor expressive language scores (Dalton et al., 2003; Braunschweig et al., 2012).”
ResultMaternal antibrain antibodies in autism
Zimmerman, A. W., Connors, S. L., Matteson, K. J., Lee, L.-C., Singer, H. S., Castaneda, J. A., & Pearce, D. A. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.08.005 · Cited by 190 · see citing works
The autoimmune basis of narcolepsy
Mahlios, J., la Herrán-Arita, A. K. D., & Mignot, E. J.-M. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.04.013 · Cited by 179 · see citing works
Brimberg, L., Sadiq, A., Gregersen, P. K., & Diamond, B. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.101 · Cited by 172 · see citing works
Immune dysfunction in autism: A pathway to treatment
Careaga, M., Water, J., & Ashwood, P. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.003 · Cited by 166 · 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
Brain‐Specific Autoantibodies in the Plasma of Subjects with Autistic Spectrum Disorder
CABANLIT, M., WILLS, S., GOINES, P., ASHWOOD, P., & VAN DE WATER, J. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1381.010 · Cited by 157 · see citing works
Self-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 · see citing works
Self-citationMaternal Autoantibodies in Autism
Braunschweig, D., & Van de Water, J. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.2506 · Cited by 122 · see citing works
Self-citationDescribing data requires no adjustment for multiple comparisons: a reply from Savitz and Olshan.
Savitz, D., & Olshan, A. (1998) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009532 · Cited by 112 · see citing works
Behavioral Correlates of Maternal Antibody Status Among Children with Autism
Braunschweig, D., Duncanson, P., Boyce, R., Hansen, R., Ashwood, P., Pessah, I. N., Hertz‐Picciotto, I., & de Water, J. V. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1378-7 · Cited by 110 · see citing works
Brief report: Ear infections in autistic and normal children
Konstantareas, M. M., & Homatidis, S. (1987) · Journal of Autism and Developmental Disorders · doi:10.1007/bf01486973 · Cited by 108 · see citing works
Enstrom, A. M., de Water, J. V., & Ashwood, P. (2009) · PubMed · Cited by 107 · see citing works
Principal pathogenetic components and biological endophenotypes in autism spectrum disorders
Sacco, R., Curatolo, P., Manzi, B., Militerni, R., Bravaccio, C., Frolli, A., Lenti, C., Saccani, M., Elia, M., Reichelt, K.-L., et al. (2010) · Autism Research · doi:10.1002/aur.151 · Cited by 102 · see citing works
Self-citationSaresella, M., Marventano, I., Guerini, F. R., Mancuso, R., Ceresa, L., Zanzottera, M., Rusconi, B., Maggioni, E., Tinelli, C., & Clerici, M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.06.020 · Cited by 98 · see citing works
Autoantibodies in Autism Spectrum Disorders (ASD)
Wills, S., Cabanlit, M., BENNETT, J., Ashwood, P., Amaral, D. G., & de Water, J. V. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1381.009 · Cited by 98 · see citing works
Nordahl, C. W., Braunschweig, D., Iosif, A.-M., Lee, A., Rogers, S., Ashwood, P., Amaral, D. G., & Van de Water, J. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.01.084 · Cited by 95 · see citing works
Coitinho, A. S., Lopes, M. H., Hajj, G. N. M., Rossato, J. I., Freitas, A. R. O., Castro, C. C., Cammarota, M., Brentani, H., Izquierdo, I., & Martins, V. R. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.01.005 · Cited by 91 · see citing works
Cluster Analysis of Autistic Patients Based on Principal Pathogenetic Components
Sacco, R., Lenti, C., Saccani, M., Curatolo, P., Manzi, B., Bravaccio, C., & Persico, A. M. (2012) · Autism Research · doi:10.1002/aur.1226 · Cited by 65 · see citing works
Self-citationThe function of cerebellar Golgi cells revisited
Schutter, E. D., Vos, B. P., & Maex, R. (2000) · Progress in brain research · doi:10.1016/s0079-6123(00)24009-0 · Cited by 61 · see citing works
Wills, S., Rossi, C. C., Bennett, J., Martínez‐Cerdeño, V., Ashwood, P., Amaral, D. G., & de Water, J. V. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-5 · Cited by 53 · see citing works
Anti-neuronal and stress-induced-phosphoprotein 1 antibodies in neuro-Behçet's disease
Vural, B., Uğurel, E., Tüzün, E., et al. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.08.008 · Cited by 29 · see citing works
Roles of Inhibitory Interneurons in the Cerebellar Cortex
Hirano, T., WATANABE, D., Kawaguchi, S., Pastan, I. H., & Nakanishi, S. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb07583.x · Cited by 26 · see citing works
Rossi, C. C., Fuentes, J., de Water, J. V., & Amaral, D. G. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-1859-y · Cited by 17 · see citing works
Watson, N. F., Ton, T. G. N., Koepsell, T. D., & Longstreth, W. T. (2012) · Sleep Medicine · doi:10.1016/j.sleep.2011.09.010 · Cited by 9 · see citing works
Otitis and autism spectrum disorders
Tajima-Pozo, K., Zambrano-Enriquez, D., de Anta, L., Zelmanova, J., Vega, J. L. D. D., & López-Ibor, J. J. (2010) · BMJ Case Reports · doi:10.1136/bcr.10.2009.2351 · Cited by 8 · see citing works
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Robinson-Agramonte, M. D. L. A., Noris García, E., Fraga Guerra, J., Vega Hurtado, Y., Antonucci, N., Semprún-Hernández, N., Schultz, S., & Siniscalco, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063033 · Cited by 176 · see citing works
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- Authors
- Piras, I. S., Haapanen, L., Napolioni, V., Sacco, R., Van de Water, J., & Persico, A. M.
- Affiliations
- Università Campus Bio-Medico (IT)
- University of California, Davis (US)
- Corresponding author
- Persico, A.M.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 38
- Pages
- 91-99
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4111628
- OpenAlex
- W2041380219
- Cited by
- 88
- References
- 39
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 9 · 2018: 10 · 2017: 2 · 2016: 10 · 2015: 8 · 2014: 6
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Unicam Scientific Publications (University of Camerino) (submittedVersion)
- Funders
- Italian Ministry for University, Scientific Research and Technology (2006058195, 2008BACT54_002)
- Italian Ministry of Health (RFPS-2007-5-640174, RF-2011-02350537 and CCM2012-Progetto NIDA, R829388)
- .S. Environmental Protection Agency
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, anti-brain antibodies, autoantibodies, maternal antibodies, autism severity, cognitive impairment, adaptive behavior, head circumference, motor stereotypies, language development, sleep disorders, familial aggregation, children, cerebellum
- MeSH terms
- Adolescent, Adult, Autoantibodies, Brain, Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Italy, Male, Middle Aged, Autoimmunity, Young Adult
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