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

Laila Al-Ayadhi,1,2 Amani Abualnaja,3 Abdullah AlZarroug,3 Turki Alharbi,3 Abdulrahman M Alhowikan,1,2 Dost M Halepoto,1 Sarah Al-Mazidi4 1Autism Research and Treatment Centre, Faculty of Medicine, King Saud University, Riyadh, 11461, Saudi Arabia; 2Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, 11461, Saudi Arabia; 3College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11432, Saudi Arabia; 4College of Medicine, Department of Physiology, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11432, Saudi ArabiaCorrespondence: Sarah Al-Mazidi, College of Medicine, Department of Physiology, Imam Mohammad Ibn Saud Islamic University, P.O Box: 5701, Riyadh, 11432, Saudi Arabia, Tel +966-553-007-441, Email [email protected]: 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 [CARS (r= − 0.11, p=0.55), SRS (r=0.11, p= 0.95), SSP (r=− 0.23, 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.Keywords: autism spectrum disorder, neuroinflammation, a disintegrin and metalloprotease 8, neurodevelopmental disorde