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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

Elevated serum levels of interleukin-17A in children with autism

Authors: Laila Yousef AL-Ayadhi, Gehan Ahmed Mostafa

Published in: Journal of Neuroinflammation | Issue 1/2012

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Abstract

Background

The T-helper (Th)1/Th2 dichotomy dominated the field of immune regulation until interleukin (IL)-17-expressing T cells (Th17) were proposed to be a third lineage of helper T cells, the key players in the pathogenesis of autoimmune disorders. Autoimmunity to brain tissue may play a pathogenic role in autism. IL-17A is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. The aim of this study was to measure serum levels of IL-17A in relation to the degree of the severity of autism.

Methods

Serum IL-17A levels were measured by ELISA in 45 children with autism and 40 matched healthy controls.

Results

Children with autism had significantly higher serum IL-17A levels than healthy controls (P <0.001), with increased serum levels of IL-17A found in 48.9% of the autism group. Patients with severe autism had significantly higher serum IL-17A levels than those with mild to moderate autism (P = 0.01), and raised serum IL-17A levels were significantly more common in children with severe autism (67.9%) than in those with mild to moderate autism (17.6%), P = 0.001.

Conclusions

Serum IL-17A levels were raised in the group with autism, and the levels correlated significantly with the severity of autism. This is the first study to measure levels of IL-17A in relation to the severity of autism, to our knowledge. Further research, with a larger subject population, is warranted to determine whether the increase of serum IL-17A levels plasma has a pathogenic role in autism, and whether anti- IL-17A therapy could be useful
Literature
1.
Dong C: Genetic controls of Th17 cell differentiation and plasticity. Exp Mol Med 2011,43(1):1–6.CrossRefPubMed
2.
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al.: Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005, 6:1123–1132.CrossRefPubMed
3.
Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al.: A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005,6(11):1133–1141.CrossRefPubMedPubMedCentral
4.
Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM: Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 2006, 24:677–688.CrossRefPubMed
5.
Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al.: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006, 441:235–238.CrossRefPubMed
6.
Schmidt-Weber CB, Akdis M, Akdis CA: TH17 cells in the big picture of immunology. J Allergy Clin Immunol 2007, 120:247–254.CrossRefPubMed
7.
Steinman L: A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 2007,13(2):139–145.CrossRefPubMed
8.
9.
10.
Shinohara ML, Kim JH, Garcia VA, Cantor H: Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 2008,29(1):68–78.CrossRefPubMedPubMedCentral
11.
Chen M, Chen G, Nie H, Zhang X, Niu X, Zang YC, et al.: Regulatory effects of IFN-beta on production of osteopontin and IL-17 by CD4+ T Cells in MS. Eur J Immunol 2009,39(9):2525–2536.CrossRefPubMed
12.
Singh VK, Warren RP, Odell JD, Warren WL, Cole P: Antibodies to myelin basic protein in children with autistic behavior. Brain Behav Immun 1993,7(1):97–103.CrossRefPubMed
13.
Singh VK, Warren RP, Averett R, Ghaziuddin M: Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol 1997,17(1):88–90.CrossRefPubMed
14.
Singh VK, Lin SX, Yang VC: Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clin Immunol Immunopathol 1998,89(1):105–108.CrossRefPubMed
15.
Mostafa GA, El-Sayed ZA, Abd El Aziz MM, El-Sayed MF: Serum anti-myelin-associated glycoprotein antibodies in Egyptian autistic children. J Child Neurol 2008, 23:1413–1418.CrossRefPubMed
16.
Mostafa GA, Al-Ayadhi LY: Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflammation 2011, 8:39.CrossRefPubMedPubMedCentral
17.
Mostafa GA, Al-Ayadhi LY: The possible link between the elevated serum levels of neurokinin A and anti-ribosomal P protein antibodies in children with autism. J Neuroinflammation 2011, 8:180.CrossRefPubMedPubMedCentral
18.
Al-Ayadhi LY, Mostafa GA: A lack of association between elevated serum levels of S100B protein and autoimmunity in autistic children. J Neuroinflammation 2012,9(1):54. [Epub ahead of print]CrossRefPubMedPubMedCentral
19.
Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN: Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol 1999, 14:388–394.CrossRefPubMed
20.
Sweeten TL, Bowyer SL, Posey DJ, Halberstadt GM, McDougle CJ: Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics 2003,112(5):420–424.CrossRef
21.
Atladóttir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, et al.: Association of Family History of autoimmune diseases and autism spectrum disorders. Pediatrics 1999,124(2):687–694.CrossRef
22.
Mostafa GA, Kitchener N: Serum anti-nuclear antibodies as a marker of autoimmunity in Egyptian autistic children. Pediatr Neurol 2009, 40:107–112.CrossRefPubMed
23.
Mostafa GA, Shehab A: The link of C4B null allele to autism and to a family history of autoimmunity in Egyptian autistic children. J Neuroimmunol 2010, 223:115–119.CrossRefPubMed
24.
Croen LA, Grether JK, Yoshida CK, Odouli R, Van de Water J: Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders.: a case–control study. Arch Pediatr Adolesc Med 2005,159(2):151–157.CrossRefPubMed
25.
Mostafa GA, Al Shehab A, Fouad NR: Increased frequency of CD4+CD25high regulatoryT cells in the peripheral blood of Egyptian children with autism. J Child Neurol 2010, 25:328–335.CrossRefPubMed
26.
Mostafa GA, El-Hadidi ES, Hewedi DH, Abdou MM: Oxidative stress in Egyptian children with autism: relation to autoimmunity. J Neuroimmunol 2010, 219:114–118.CrossRefPubMed
27.
Warren RP, Singh VK, Cole P, Odell JD, Pingree CB, Warren WL, White E: Increased frequency of the null allele at the complement C4b locus in autism. Clin Exp Immunol 1991, 83:438–440.CrossRefPubMedPubMedCentral
28.
Odell D, Maciulis A, Cutler A, Warren L, McMahon WM, Coon H, et al.: Confirmation of the association of C4B null allele in autism. Human Immunol 2005,6(2):140–145.CrossRef
29.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th edition. American Psychiatric Association, Washington DC; 1994.
30.
Schopler E, Reichler RJ, Renner BR: The Childhood Autism Rating Scale (CARS), for Diagnostic Screening and Classification in Autism. Irvington, New York, NY; 1986.
31.
Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, et al.: Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010,2(52):52–72.CrossRef
32.
Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, et al.: Transforming growth factor-beta induces development of the T(H) 17 lineage. Nature 2006, 441:231–234.CrossRefPubMed
33.
Onore C, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Van de Water J, et al.: Decreased cellular IL-23 but not IL-17 production in children with autism spectrum disorders. J Neuroimmunol 2009,216(1–2):126–129.CrossRefPubMedPubMedCentral
34.
Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, et al.: Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One 2011,6(5):e20470.CrossRefPubMedPubMedCentral
35.
Garrett-Sinha LA, John S, Gaffen SL: IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol 2008, 20:519–525.CrossRefPubMed
36.
Nguyen CQ, Hu MH, Li Y, Stewart C, Peck AB: Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjogren’s syndrome: findings in humans and mice. Arthritis Rheum 2008, 58:734–743.CrossRefPubMedPubMedCentral
37.
Sakai A, Sugawara Y, Kuroishi T, Sasano T, Sugawara S: Identification of IL-18 and Th17 cells in salivary glands of patients with Sjogren’s syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol 2008, 181:2898–2906.CrossRefPubMed
38.
39.
Jadidi-Niaragh F, Mirshafiey A: Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol 2011,74(1):1–13.CrossRefPubMed
40.
41.
van Beelen AJ, Zelinkova Z, Taanman-Kueter EW, Muller FJ, Hommes DW, Zaat SA, et al.: Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 2007, 27:660–669.CrossRefPubMed
42.
Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F: Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 2007, 8:942–949.CrossRefPubMed
43.
Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupé P, Barillot E, et al.: A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 2008, 9:650–657.CrossRefPubMed
44.
Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al.: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006, 126:1121–1133.CrossRefPubMed
45.
Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, et al.: T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORalpha and RORgamma. Immunity 2008, 28:29–39.CrossRefPubMed
46.
Gerosa F, Baldani-Guerra B, Lyakh LA, Batoni G, Esin S, Winkler-Pickett RT, et al.: Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells. J Exp Med 2008, 205:1447–1461.CrossRefPubMedPubMedCentral
47.
Khader SA, Gaffen SL, Kolls JK: Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol 2009, 2:403–411.CrossRefPubMedPubMedCentral
48.
49.
Bettelli E, Korn T, Oukka M, Kuchroo VK: Induction and effector functions of T(H)17 cells. Nature 2008, 453:1051–1057.CrossRefPubMed
50.
Murugaiyan G, Mittal A, Weiner HL: Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol 2008,181(11):7480–7488.CrossRefPubMedPubMedCentral
51.
Al-Ayadhi LY, Mostafa GA: Increased serum osteopontin levels in autistic children: Relation to the disease severity. Brain Behav Immun 2011,25(7):1393–1398.CrossRefPubMed
52.
53.
54.
Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock K, Vojdani E: Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. J Neuroimmunol 2002,129(1–2):168–177.CrossRefPubMed
55.
Mostafa GA, Al-Ayadhi LY: A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children. J Neuroinflammation 2011, 8:71.CrossRefPubMedPubMedCentral
56.
Singh VK: Plasma increase of interleukin-12 and interferon-gamm. Pathological significance in autism. J Neuroimmunol 1996,66(1–2):143–145.CrossRefPubMed
57.
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J: Altered T cell responses in children with autism. Brain Behav Immun 2011,25(5):840–849.CrossRefPubMed
58.
Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, et al.: Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 2009, 30:108–119.CrossRefPubMed
59.
Lin Y, Ritchea S, Logar A, Slight S, Messmer M, Rangel-Moreno J, et al.: Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. Immunity 2009, 31:799–810.CrossRefPubMedPubMedCentral
Metadata
Title
Elevated serum levels of interleukin-17A in children with autism
Authors
Laila Yousef AL-Ayadhi
Gehan Ahmed Mostafa
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-158

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