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Imbalance in pro-inflammatory and anti-inflammatory cytokines milieu in B cells of children with autism.

Molecular immunology2022

Nadeem Ahmed, Ahmad Sheikh F, Al-Harbi Naif O, Al-Ayadhi Laila Y, Sarawi Wedad, Attia Sabry M, Bakheet Saleh A, Alqarni Saleh A, Ali Nemat, AsSobeai Homood M

What this study means for families

Researchers studied immune cells called B cells in children with autism compared to typical children. They found that B cells in autistic children produce more inflammation-causing proteins and fewer inflammation-reducing proteins. This suggests the immune system in autism may be out of balance, with too much inflammation. When exposed to bacterial toxins, this imbalance became even worse in the autism group. This research helps explain why immune problems are common in autism.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Research summary

This study examined immune dysfunction in autism by analyzing inflammatory and anti-inflammatory proteins (cytokines) produced by B cells - a type of immune cell. Researchers compared B cells from children with autism spectrum disorder (ASD) to typically developing children. They found that B cells from children with ASD produced higher levels of inflammatory cytokines (IL-6, TNF-α) and lower levels of anti-inflammatory cytokines (IL-10), suggesting an imbalanced immune response. When B cells were exposed to a bacterial component (LPS), this inflammatory imbalance was further amplified in the ASD group.

Treatment with an NF-kB inhibitor partially reduced this inflammatory response. The findings suggest B cells may contribute to immune dysfunction in autism through dysregulated cytokine production.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Key findings

  • 1

    B cells from children with ASD showed elevated inflammatory cytokines IL-6 and TNF-α compared to typically developing controls

    Confidence: The abstract clearly states these findingsRelevance: Suggests chronic inflammatory state in immune cells of autistic children
  • 2

    Anti-inflammatory cytokine IL-10 was decreased in B cells of ASD subjects compared to controls

    Confidence: Explicitly stated in the abstractRelevance: Indicates reduced capacity to control inflammation in autism
  • 3

    LPS stimulation further increased IL-6 expression in ASD B cells but had no significant effect on IL-10

    Confidence: Clearly reported experimental findingRelevance: Suggests heightened inflammatory response to bacterial triggers in autism

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Clinical implications

Findings suggest immune dysfunction in autism involves B cell dysregulation with pro-inflammatory bias. This may inform understanding of comorbid conditions and potential therapeutic targets. However, clinical significance requires validation in larger studies with detailed participant characterization and longitudinal follow-up.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Limitations

Sample size not reported in abstract. Study type unclear. Cross-sectional design cannot establish causality. Limited to cytokine analysis in B cells only. No information about participant characteristics, age ranges, or potential confounding factors provided in abstract.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Original abstract

B cells play multiple roles in preservation of healthy immune system including management of immune responses by expression of pro- and anti-inflammatory cytokines. Several earlier studies have documented that B cells express both pro-inflammatory cytokines such as IL-6, TNF-α as well as anti-inflammatory cytokines such as IL-10. However, it is yet to be examined whether these pro-/anti-inflammatory cytokines are expressed in B cells of children with autism spectrum disorder (ASD). Pathophysiology of ASD begins in early childhood and is characterized by repetitive/restricted behavioral patterns, and dysfunction in communal/communication skills.

ASD pathophysiology also has a strong component of immune dysfunction which has been highlighted in numerous earlier publications. In this study, we specifically explored pro-/anti-inflammatory cytokines (IL-6, IL-17A, IFN-γ, TNF-α, IL-10) in B cells of ASD subjects and compared them typically developing control (TDC) children. Present study shows that inflammatory cytokines such as IL-6 and TNF-α are elevated in B cells of ASD subjects, while anti-inflammatory cytokine, IL-10 is decreased in ASD group when compared to TDC group. Further, TLR4 activation by its ligand, lipopolysaccharide (LPS) further upregulates inflammatory potential of B cells from ASD group by increasing IL-6 expression, whereas LPS has no significant effect on IL-10 expression in ASD group.

Furthermore, LPS-induced inflammatory signaling of IL-6 in B cells of ASD subjects was partially mitigated by the pretreatment with NF-kB inhibitor. Present study propounds the idea that B cells could be crucial players in causing immune dysfunction in ASD subjects through an imbalance in expression of pro-/anti-inflammatory cytokines.

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Evidence Grade

Emerging

limited

Grade assigned by AutismInsights based on study type and published abstract.

Study Details

Journal
Molecular immunology
Year
2022
PMID
34915269
DOI
10.1016/j.molimm.2021.12.009

MeSH Terms

Anti-Inflammatory AgentsAutism Spectrum DisorderAutistic DisorderB-LymphocytesCase-Control StudiesChildChild, PreschoolCytokinesFemaleHumansImmunityInflammationMaleMonocytesSignal TransductionUp-Regulation