title: Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children.
abstract: Accumulating evidence suggests an association between immune dysfunction and autism disorders in a significant subset of children. In addition, an imbalance between pro- and anti-inflammatory pathways has been proposed to play an important role in the pathogenesis of several neurodevelopmental disorders including autism; however, the role of anti-inflammatory molecules IL-27 and CTLA-4 and pro-inflammatory cytokines IL-21 and IL-22 has not previously been explored in autistic children. In the current study, we investigated the expression of IL-21, IL-22, IL-27, and CD152 (CTLA-4) following an in-vitro immunological challenge of peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically-developing children (TD) with phorbol-12-myristate 13-acetate (PMA) and ionomycin. In our study, cells from children with AU had increased IL-21 and IL-22 and decreased CTLA-4 expression on CD4+T cells as compared with cells from the TD control. Similarly, AU cells showed decreased IL-27 production by CD14+cells compared to that of TD control cells. These results were confirmed by real-time PCR and western blot analyses. Our study shows dysregulation of the immune balance in cells from autistic children as depicted by enhanced pro-inflammatory cytokines, 'IL-21/IL-22' and decreased anti-inflammatory molecules, 'IL-27/CTLA-4'. Thus, further study of this immune imbalance in autistic children is warranted in order to facilitate development of biomarkers and therapeutics.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fashaikh@ksu.edu.sa.
authors.forename: Sheikh F
authors.initials: SF
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mushtaq A
authors.initials: MA
authors.lastname: Ansari
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Bakheet
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Sabry M
authors.initials: SM
authors.lastname: Attia
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Cell Biology, National Research Center, Cairo, Egypt.
authors.forename: Khairy M A
authors.initials: KM
authors.lastname: Zoheir
authors.affiliation: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Laila Yousef
authors.initials: LY
authors.lastname: Al-Ayadhi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad Z
authors.initials: MZ
authors.lastname: Alzahrani
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdulaziz M S
authors.initials: AM
authors.lastname: Alsaad
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Moureq R
authors.initials: MR
authors.lastname: Alotaibi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Adel R A
authors.initials: AR
authors.lastname: Abd-Allah
mesh_terms: D001321:Autistic Disorder / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D060908:CTLA-4 Antigen / Q000096:biosynthesis / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D000097043:Interleukin-22; D000098546:Interleukin-21
chemical_list: D015415:Biomarkers; D060908:CTLA-4 Antigen; D016207:Cytokines; D007378:Interleukins; D000097043:Interleukin-22; D000098546:Interleukin-21; C464565:MYDGF protein, human
keywords: CD152 (CTLA-4); Children with autism; Cytokines; Peripheral blood mononuclear cells (PBMCs); Typically developing children