Determination of neuroinflammatory biomarkers in autistic and neurotypical Saudi children

Hamed, Najat; Laila-Al-Ayadhi,; Osman, Mohamed A.; Elkhawad, Abdalla Omer; Bjørklund, Geir; Qasem, Hanan; Zayed, Naima; El‐Ansary, Afaf

doi:10.1007/s11011-019-00420-5

Cited by 5 publications

(7 citation statements)

References 69 publications

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“…The mean age ± standard deviation (SD) was 7.06 ± 0.70 and 7.17 ± 0.46 years for the autism and control groups, respectively. In Table 1 , the age of subjects ranged from 2 to 12 years, apart from seven studies in which subjects reached 13, 14, 16, 21, and 28 years ( 22 – 24 , 40 , 46 , 48 , 49 ). Studies on MCP-1 and MIP-1α bloodspots were performed using neonatal samples ( 7 , 8 , 10 , 11 ).…”

Section: Resultsmentioning

confidence: 99%

“…Unlike other cytokines that are produced in their active forms, TGF-β is secreted in an inactive form and stored in the extracellular matrix as a latent complex with its prodomain, which can then be converted into the active form through multiple mechanisms ( 86 ). In this review, studies showing decreased TGF-β levels specifically involved the TGF-β1 isoform ( 35 , 50 , 51 ), whereas increased levels of TGF-β were found for either the TGF-β2 or TGF-β1 isoform ( 39 , 46 , 48 ). Among these studies, only the functional form of TGF-β was reported in some studies, in which the activated form of TGF-β was specifically analyzed ( 35 , 46 , 50 ).…”

Section: Discussionmentioning

confidence: 97%

“…However, results for TGF-β are conflicting, whereby it is reported to be both increased ( 39 , 46 , 48 ) and decreased ( 35 , 50 , 51 ) in the plasma of individuals with autism, and there is scarce evidence concerning its cell of origin in autism. This discrepancy in TGF-β results might be due to differences between the studies in the isoforms or functional forms being assessed.…”

Section: Discussionmentioning

confidence: 99%

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In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies

Nour‐Eldine

Ltaief²,

Manaph³

et al. 2022

Front. Immunol.

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Abnormal cytokine levels in circulating blood have been repeatedly reported in autism; however, the underlying cause remains unclear. This systematic review aimed to investigate cytokine levels in peripheral blood compartments and identify their potential immune cellular sources in subjects with autism through comparison with controls. We conducted an electronic database search (PubMed, Scopus, ProQuest Central, Ovid, SAGE Journals, and Wiley Online Library) from inception (no time limits) to July 9, 2020, and identified 75 relevant articles. Our qualitative data synthesis focused on results consistently described in at least three independent studies, and we reported the results according to the PRISMA protocol. We found that compared with controls, in subjects with autism, cytokines IL-6, IL-17, TNF-α, and IL-1β increased in the plasma and serum. We also identified monocytes, neutrophils, and CD4+ T cells as potential sources of these elevated cytokines in autism. Cytokines IFN-γ, TGF-β, RANTES, and IL-8 were increased in the plasma/serum of subjects with autism, and IFN-γ was likely produced by CD4+ T cells and natural killer (NK) cells, although conflicting evidence is present for IFN-γ and TGF-β. Other cytokines—IL-13, IL-10, IL-5, and IL-4—were found to be unaltered in the plasma/serum and post-stimulated blood immune cells in autistic individuals as compared with controls. The frequencies of T cells, monocytes, B cells, and NK cells were unchanged in subjects with autism as opposed to controls, suggesting that abnormal cytokines were unlikely due to altered cell numbers but might be due to altered functioning of these cells in autism. Our results support existing studies of abnormal cytokines in autism and provide comprehensive evidence of potential cellular sources of these altered cytokines in the context of autism.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205224, identifier [CRD42020205224].

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies

Nour‐Eldine

Ltaief²,

Manaph³

et al. 2022

Front. Immunol.

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“…Three The Mean (SD) values of total SRS scores of all the ASD, severe and mild-to-moderate ASD categories were found to be 119 (44), 134 (43) and 102 (39), respectively, which are considered severe and are strongly linked with a clinical diagnosis of ASD. Also, the SSP measured sensory processing dysfunction and showed a mean (SD) score of 153 (29) in children with ASD (Figure 1).…”

Section: Resultsmentioning

confidence: 92%

A Disintegrin and Metalloproteinase Protein 8 (ADAM 8) in Autism Spectrum Disorder: Links to Neuroinflammation

Al-Ayadhi¹,

Abualnaja²,

AlZarroug³

et al. 2023

NDT

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Background: Converging lines of evidence confirmed neuroinflammation's role in autism spectrum disorder (ASD) etiological pathway. A disintegrin and metalloproteinase 8 (ADAM8) play major roles in inflammatory and allergic processes in various diseases. Aim: This study aimed to investigate ADAM8 plasma levels in autistic children compared to healthy controls. Also, to discover the association between ADAM8, disease severity, and neuroinflammation in ASD. Methodology: This case-control study included children with ASD (n=40) and aged-matched healthy controls (n=40). The plasma levels of the ADAM 8 were determined using enzyme-linked immunosorbent assay (ELISA). The assessment of ASD severity and social and sensory behaviors were categorized as mild, moderate and severe. Correlations among ADAM8 plasma levels and ASD severity scores [Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS) and Short Sensory Profile (SSP)] were obtained by Spearman correlation coefficient (r). Results: ASD children (n=40), including severe autism (n=21) and mild-to-moderate autism (n=19), showed significantly (p ≤ 0.05) lower plasma levels of ADAM8 [4683 (2885-5229); 4663 (4060-5000); 4632 (2885-5229)], respectively, than those of healthy controls [5000 (4047-5000)] [median (IQR) pg/mL]. However, there was no significant difference between the ADAM8 levels of children with severe and mild-to-moderate autism (p = 0.71). Moreover, ADAM8 plasma levels were not significantly correlated with the severity of ASD measured by behavioral scales p=0.55), SRS (r=0.11, p= 0.95), p=0.23)]. Conclusion:The low ADAM8 plasma levels in children with ASD possibly indicated that ADAM8 might be implicated in the pathogenesis of ASD but not in the severity of the disease. These results should be interpreted with caution until additional studies are carried out with larger populations to decide whether the reduction in plasma ADAM8 levels is a mere consequence of ASD or if it plays a pathogenic role in the disease.

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“…Musto and Rana indicated that peripheral inflammation leads to central inflammation because of the blood-brain barrier breakdown and is necessary to conduct further studies to show the relationship between systemic inflammation and epilepsy for prevention and treatment (21). Hamed et al (22) reported some neuroinflammatory biomarkers for early diagnosis of autism in plasma and also showed the usefulness of TGF-β2, hematopoietic prostaglandin D2 synthase (H-PGDS) and heat shock protein 70 (HSP70) as diagnostic markers to differentiate between autism spectrum disorder and control.…”

Section: Discussionmentioning

confidence: 99%

Can Hematological Parameters Indicate Possible Inflammatory Mechanisms in Children with Intellectual Disability?

Ustkoyuncu¹

2020

Erciyes Med J

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This study aims to interpret the hematological parameters of children with the intellectual disability and to show the relationship between hematological parameters and possible inflammatory mechanisms of intellectual disability. Materials and Methods: In this study, 50 children with the intellectual disability (32 males, 18 females) and 40 healthy individuals (25 males, 15 females) were retrospectively screened. Lymphocyte and platelet count, white blood cell count, neutrophil, platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW) and mean platelet volume (MPV) were recorded for both groups and compared. Results: Neutrophil to lymphocyte ratio and neutrophil counts in the intellectual disability group were elevated than control. Mean platelet volume in the intellectual disability group was higher than the control and red cell distribution width in children with the intellectual disability was elevated than control. We did not detect any statistical difference in neutrophil to lymphocyte ratio between the groups with or without inborn error of metabolism. Conclusion: The findings obtained in this study suggest that we can use mean platelet volume, neutrophil to lymphocyte ratio and red cell distribution width as inflammatory markers for the intellectual disability of children.

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Determination of neuroinflammatory biomarkers in autistic and neurotypical Saudi children

Cited by 5 publications

References 69 publications

In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies

In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies

A Disintegrin and Metalloproteinase Protein 8 (ADAM 8) in Autism Spectrum Disorder: Links to Neuroinflammation

Can Hematological Parameters Indicate Possible Inflammatory Mechanisms in Children with Intellectual Disability?

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