Detection of antinuclear and antilaminin antibodies in autistic children who received thimerosal-containing vaccines

Singh, Vijendra K.; Rivas, Wyatt H.

doi:10.1007/bf02256125

Cited by 17 publications

(14 citation statements)

References 9 publications

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“…In fact, in ASD numerous antibodies directed against brain or central nervous system tissue have been identified (reviewed in [2]). The targets of these antibodies are quite diverse and include serotonin receptors [40], MBP [41], nucleus [42], and GFAP [43], as well as numerous unidentified protein targets. Moreover, unique autoantibody targets seem to be found only in subsets of children with ASD, and their detection has been difficult to replicate across studies; primary examples are antibodies against such targets as MBP and GFAP [8, 9].…”

Section: Discussionmentioning

confidence: 99%

Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders

Careaga

Hansen

Hertz-Piccotto

et al. 2013

Mediators of Inflammation

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Autism spectrum disorders (ASD) are characterized by impairments in communication, social interactions, and repetitive behaviors. While the etiology of ASD is complex and likely involves the interplay of genetic and environmental factors, growing evidence suggests that immune dysfunction and the presence of autoimmune responses including autoantibodies may play a role in ASD. Anti-phospholipid antibodies are believed to occur from both genetic and environmental factors and have been linked to a number of neuropsychiatric symptoms such as cognitive impairments, anxiety, and repetitive behaviors. In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in a cross-sectional analysis of plasma of young children with ASD compared to age-matched typically developing (TD) controls and children with developmental delays (DD) other than ASD. We found that levels of anti-cardiolipin, β2-glycoprotein 1, and anti-phosphoserine antibodies were elevated in children with ASD compared with age-matched TD and DD controls. Further, the increase in antibody levels was associated with more impaired behaviors reported by parents. This study provides the first evidence for elevated production of anti-phospholipid antibodies in young children with ASD and provides a unique avenue for future research into determining possible pathogenic mechanisms that may underlie some cases of ASD.

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Section: Discussionmentioning

confidence: 99%

Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders

Careaga

Hansen

Hertz-Piccotto

et al. 2013

Mediators of Inflammation

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“…PTEN is a major upstream regulator in the mTOR pathway, and mutations in this protein are associated with higher rates of ASD. 46 In an animal model with PTEN-deficient cells, Foxp3, a putative controller for the generation of regulatory T-cells, was found to be downregulated, 88 leading to decreased number of cells that suppress immune responses and thus favoring immune dysfunction, activa- 63 (1993) Myelin basic protein (MBP) Positive Singh et al 64 (1997) Neuron-axon acidic protein (NAFP); glial fibrillary acidic protein (GFAP) Positive Singh et al 65 (1998) Myelin basic protein (MBP); neuron-axon filament Positive Evers et al 66 (2002) Heat shock protein 90 (HSP90) Positive Vodjani et al 67 (2004) Gliadin; cerebellar peptides; heat shock protein 60 (HSP60) Positive Singh et al 68 (2004) Caudate nucleus; cerebral cortex; cerebellum Positive Singh et al 69 (2004) Nucleus and laminin Negative Silva et al 20 (2004) Unknown ϳ20 kDa protein Positive* Connolly et al 70 69 found a positive finding for a ϳ20 kDa protein, but determined it not to be MBP. (1998) tion, or both.…”

Section: Deficits In Immune and Neurological Signaling Pathwaysmentioning

confidence: 99%

Immune Dysfunction in Autism: A Pathway to Treatment

2010

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Summary: Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.

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“…As critical regulators of immune responses in the periphery and in the brain, dysfunction in the monocyte cell lineage may play a key role in the generation of immune abnormalities observed in ASD, including potential autoimmune responses (Cabanlit et al, 2007; Connolly et al, 2006; Connolly et al, 1999; Kozlovskaia et al, 2000; Silva et al, 2004; Singh and Rivas, 2004a; Singh and Rivas, 2004b; Todd et al, 1988; Wills et al, 2009). In addition, as the phenotype of stimulated microglia described in brain tissues from individuals with ASD (Vargas et al, 2005) closely resembles activated monocytes/macrophages (Hess et al, 2004), the study of in vitro monocyte responses following stimulation may increase our understanding of the mechanisms underlying altered innate immune responses in the brain of individuals with ASD.…”

Section: Introductionmentioning

confidence: 99%

Differential monocyte responses to TLR ligands in children with autism spectrum disorders

Enstrom¹,

Onore²,

Water

et al. 2010

Brain, Behavior, and Immunity

252

207

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Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. Recent evidence has suggested that impairments of innate immunity may play an important role in ASD. To test this hypothesis, we isolated peripheral blood monocytes from 17 children with ASD and 16 agematched typically developing (TD) controls and stimulated these cell cultures in vitro with distinct toll-like receptors (TLR) ligands: TLR2 (lipoteichoic acid; LTA), TLR3 (poly I:C), TLR4 (lipopolysaccharide; LPS), TLR5 (flagellin) and TLR9 (CpG-B). Supernatants were harvested from the cell cultures and pro-inflammatory cytokine responses for IL-1β, IL-6, IL-8, TNFα, MCP-1, and GM-CSF were determined by multiplex Luminex analysis. After in vitro challenge with TLR ligands, differential cytokine responses were observed in monocyte cultures from children with ASD compared with TD control children. In particular, there was a marked increase in pro-inflammatory IL-1β, IL-6 and TNFα responses following TLR2, and IL-1β response following TLR4 stimulation in monocyte cultures from children with ASD (p<0.04). Conversely, following TLR9 stimulation there was a decrease in IL-1β, IL-6, GM-CSF and TNFα responses in monocyte cell cultures from children with ASD compared with controls (p<0.05). These data indicate that, monocyte cultures from children with ASD are more responsive to signaling via select TLRs. As monocytes are key regulators of the immune response, dysfunction in the response of these cells could result in long-term immune alterations in children with ASD that may lead to the development of adverse neuroimmune interactions and could play a role in the pathophysiology observed in ASD.

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Detection of antinuclear and antilaminin antibodies in autistic children who received thimerosal-containing vaccines

Cited by 17 publications

References 9 publications

Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders

Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders

Immune Dysfunction in Autism: A Pathway to Treatment

Differential monocyte responses to TLR ligands in children with autism spectrum disorders

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