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Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Research

Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity

Authors: Gehan A Mostafa, Laila Y AL-ayadhi

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Autoimmunity to the central nervous system (CNS) may play a pathogenic role in a subgroup of patients with autism. This study aimed to investigate the frequency of serum anti-ganglioside M1 auto-antibodies, as indicators of the presence of autoimmunity to CNS, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism.

Methods

Serum anti-ganglioside M1 antibodies were measured, by ELISA, in 54 autistic children, aged between 4 and 12 years, in comparison to 54 healthy-matched children. Autistic severity was assessed by using the Childhood Autism Rating Scale (CARS).

Results

Autistic children had significantly higher serum levels of anti-ganglioside M1 antibodies than healthy children (P < 0.001). The seropositivity of anti-ganglioside M1 antibodies was found in 74% (40/54) of autistic children. Serum levels of anti-ganglioside M1 antibodies were significantly higher in autistic children with severe autism (63%) than those with mild to moderate autism (37%), P = 0.001. Moreover, serum anti-ganglioside M1 antibodies had significant positive correlations with CARS (P < 0.001).

Conclusions

Serum levels of anti-ganglioside M1 antibodies were increased in many autistic children. Also, their levels had significant positive correlations with the degree of the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the possible etiopathogenic role of anti-ganglioside M1 auto-antibodies in autism. The role of immunotherapy in autistic patients who have increased serum levels of anti-ganglioside M1 antibodies should also be studied.
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Literature
1.
go back to reference Dalton R, Forman MA, Boris NW: Pervasive developmental disorders and childhood psychosis. Nelson textbook of Pediatrics. Edited by: Behrman RE, Kliegman RM, Jenson HB. 2004, Philadelphia: WB Saunders, 93-94. 17 Dalton R, Forman MA, Boris NW: Pervasive developmental disorders and childhood psychosis. Nelson textbook of Pediatrics. Edited by: Behrman RE, Kliegman RM, Jenson HB. 2004, Philadelphia: WB Saunders, 93-94. 17
2.
3.
go back to reference Vojdani A, Pangborn JB, Vojdani E, Cooper EL: Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major investigators of autoimmunity in autism. Int J Immunopathol Pharmacol. 2003, 16 (3): 189-99.PubMed Vojdani A, Pangborn JB, Vojdani E, Cooper EL: Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major investigators of autoimmunity in autism. Int J Immunopathol Pharmacol. 2003, 16 (3): 189-99.PubMed
4.
go back to reference 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. 10.1177/0883073808319321.CrossRefPubMed 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. 10.1177/0883073808319321.CrossRefPubMed
5.
go back to reference 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. 10.1542/peds.112.5.e420.CrossRef 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. 10.1542/peds.112.5.e420.CrossRef
6.
go back to reference Mostafa GA, Kitchener N: Serum anti-nuclear antibodies as a marker of autoimmunity in Egyptian autistic children. Pediatr Neurol. 2009, 40: 107-112. 10.1016/j.pediatrneurol.2008.10.017.CrossRefPubMed Mostafa GA, Kitchener N: Serum anti-nuclear antibodies as a marker of autoimmunity in Egyptian autistic children. Pediatr Neurol. 2009, 40: 107-112. 10.1016/j.pediatrneurol.2008.10.017.CrossRefPubMed
7.
go back to reference 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. 10.1016/j.jneuroim.2010.03.025.CrossRefPubMed 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. 10.1016/j.jneuroim.2010.03.025.CrossRefPubMed
8.
go back to reference 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. 10.1016/j.jneuroim.2009.12.003.CrossRefPubMed 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. 10.1016/j.jneuroim.2009.12.003.CrossRefPubMed
9.
go back to reference Mostafa GA, Al Shehab A, Fouad NR: Frequency of CD4+CD25high regulatoryT cells in the peripheral blood of Egyptian children with autism. J Child Neurol. 2010, 25: 328-335. 10.1177/0883073809339393.CrossRefPubMed Mostafa GA, Al Shehab A, Fouad NR: Frequency of CD4+CD25high regulatoryT cells in the peripheral blood of Egyptian children with autism. J Child Neurol. 2010, 25: 328-335. 10.1177/0883073809339393.CrossRefPubMed
10.
go back to reference Torres AR, Maciulis A, Odell D: The association of MHC genes with autism. Front Biosci. 2001, 6: 936-943. 10.2741/Torres.CrossRef Torres AR, Maciulis A, Odell D: The association of MHC genes with autism. Front Biosci. 2001, 6: 936-943. 10.2741/Torres.CrossRef
11.
go back to reference 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, 66 (2): 140-145. 10.1016/j.humimm.2004.11.002.CrossRef 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, 66 (2): 140-145. 10.1016/j.humimm.2004.11.002.CrossRef
12.
go back to reference Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, et al: Enterocolitis in children with developmental disorders. Am J Gastroenterol. 2000, 95 (9): 2285-2295. 10.1111/j.1572-0241.2000.03248.x.CrossRefPubMed Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, et al: Enterocolitis in children with developmental disorders. Am J Gastroenterol. 2000, 95 (9): 2285-2295. 10.1111/j.1572-0241.2000.03248.x.CrossRefPubMed
13.
go back to reference Ariga T, McDonald MP, Yu RK: Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease--a review. J Lipid Res. 2008, 49 (6): 1157-1175. 10.1194/jlr.R800007-JLR200.PubMedCentralCrossRefPubMed Ariga T, McDonald MP, Yu RK: Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease--a review. J Lipid Res. 2008, 49 (6): 1157-1175. 10.1194/jlr.R800007-JLR200.PubMedCentralCrossRefPubMed
14.
go back to reference Zitman FM, Todorov B, Jacobs BC, Verschuuren JJ, Furukawa K, Furukawa K, et al: Neuromuscular synaptic function inmice lacking major subsets of gangliosides. Neuroscience. 2008, 156 (4): 885-897. 10.1016/j.neuroscience.2008.08.034.CrossRefPubMed Zitman FM, Todorov B, Jacobs BC, Verschuuren JJ, Furukawa K, Furukawa K, et al: Neuromuscular synaptic function inmice lacking major subsets of gangliosides. Neuroscience. 2008, 156 (4): 885-897. 10.1016/j.neuroscience.2008.08.034.CrossRefPubMed
15.
go back to reference Zitman FM, Todorov B, Verschuuren JJ, Jacobs BC, Furukawa K, Furukawa K, et al: Neuromuscular synaptic transmission in aged ganglioside-deficient mice. Neurobiol Aging. 2011, 32 (1): 157-167. 10.1016/j.neurobiolaging.2009.01.007.CrossRefPubMed Zitman FM, Todorov B, Verschuuren JJ, Jacobs BC, Furukawa K, Furukawa K, et al: Neuromuscular synaptic transmission in aged ganglioside-deficient mice. Neurobiol Aging. 2011, 32 (1): 157-167. 10.1016/j.neurobiolaging.2009.01.007.CrossRefPubMed
16.
go back to reference Zitman FM, Todorov B, Furukawa K, Furukawa K, Willison HJ, Plomp JJ: Totalganglioside ablation at mouse motor nerve terminals alters neurotransmitter release level. Synapse. 2010, 64 (4): 335-338. 10.1002/syn.20747.CrossRefPubMed Zitman FM, Todorov B, Furukawa K, Furukawa K, Willison HJ, Plomp JJ: Totalganglioside ablation at mouse motor nerve terminals alters neurotransmitter release level. Synapse. 2010, 64 (4): 335-338. 10.1002/syn.20747.CrossRefPubMed
17.
go back to reference Kato T, Hatanaka K: Purification of gangliosides by liquid-liquid partitionchromatography. J Lipid Res. 2008, 49 (11): 2474-2478. 10.1194/jlr.D800033-JLR200.CrossRefPubMed Kato T, Hatanaka K: Purification of gangliosides by liquid-liquid partitionchromatography. J Lipid Res. 2008, 49 (11): 2474-2478. 10.1194/jlr.D800033-JLR200.CrossRefPubMed
18.
go back to reference Sugiura Y, Shimma S, Konishi Y, Yamada MK, Setou M: Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglioside molecular species in the mouse hippocampus. PLoS ONE. 2008, 3 (9): e3232-10.1371/journal.pone.0003232.PubMedCentralCrossRefPubMed Sugiura Y, Shimma S, Konishi Y, Yamada MK, Setou M: Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglioside molecular species in the mouse hippocampus. PLoS ONE. 2008, 3 (9): e3232-10.1371/journal.pone.0003232.PubMedCentralCrossRefPubMed
19.
go back to reference Ribeiro CM, Vasconcelos BC, Silva Neto JC, Silva VA, Figueiredo NG: Histopathological analysis of gangliosides use in peripheral nerve regeneration after axonotmesis in rats. Acta Cir Bras. 2008, 23 (4): 364-371.CrossRefPubMed Ribeiro CM, Vasconcelos BC, Silva Neto JC, Silva VA, Figueiredo NG: Histopathological analysis of gangliosides use in peripheral nerve regeneration after axonotmesis in rats. Acta Cir Bras. 2008, 23 (4): 364-371.CrossRefPubMed
20.
go back to reference Plomp JJ, Willison HJ: Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction. J Physiol. 2009, 587 (Pt 16): 3979-3999.PubMedCentralCrossRefPubMed Plomp JJ, Willison HJ: Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction. J Physiol. 2009, 587 (Pt 16): 3979-3999.PubMedCentralCrossRefPubMed
21.
go back to reference Ravindranath MH, Muthugounder S, Saravanan TS, Presser N, Morton DL: Human antiganglioside antibodies: validation of ELISA. Ann NY Acad Sci. 2005, 1050: 229-242. 10.1196/annals.1313.024.CrossRefPubMed Ravindranath MH, Muthugounder S, Saravanan TS, Presser N, Morton DL: Human antiganglioside antibodies: validation of ELISA. Ann NY Acad Sci. 2005, 1050: 229-242. 10.1196/annals.1313.024.CrossRefPubMed
22.
go back to reference Watanabe O, Arimura K: Pathomechanism of autoantibody production inneurological disorders. Nippon Rinsho. 2008, 66 (6): 1065-1072.PubMed Watanabe O, Arimura K: Pathomechanism of autoantibody production inneurological disorders. Nippon Rinsho. 2008, 66 (6): 1065-1072.PubMed
23.
go back to reference Greenwood DL, Gitlits VM, Alderuccio F, Sentry JW, Toh BH: Autoantibodies in neuropsychiatric lupus. Autoimmunity. 2002, 35 (2): 79-86. 10.1080/08916930290016547.CrossRefPubMed Greenwood DL, Gitlits VM, Alderuccio F, Sentry JW, Toh BH: Autoantibodies in neuropsychiatric lupus. Autoimmunity. 2002, 35 (2): 79-86. 10.1080/08916930290016547.CrossRefPubMed
24.
go back to reference Mostafa GA, Ibrahim DH, Al Shehab A, Mohammed AK: The role of measurement of serum autoantibodies in prediction of pediatric neuropsychiatric systemic lupus erythematosus. J Neuroimmunol. 2010, 227: 195-201. 10.1016/j.jneuroim.2010.07.014.CrossRefPubMed Mostafa GA, Ibrahim DH, Al Shehab A, Mohammed AK: The role of measurement of serum autoantibodies in prediction of pediatric neuropsychiatric systemic lupus erythematosus. J Neuroimmunol. 2010, 227: 195-201. 10.1016/j.jneuroim.2010.07.014.CrossRefPubMed
25.
go back to reference Kusunoki S, Kaida K: Antibodies against ganglioside complexes in Guillain-Barré syndrome and related disorders. J Neurochem. 2011, 116 (5): 828-832. 10.1111/j.1471-4159.2010.07029.x.CrossRefPubMed Kusunoki S, Kaida K: Antibodies against ganglioside complexes in Guillain-Barré syndrome and related disorders. J Neurochem. 2011, 116 (5): 828-832. 10.1111/j.1471-4159.2010.07029.x.CrossRefPubMed
26.
go back to reference American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 1994, Washington DC: American Psychiatric Association, 4 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 1994, Washington DC: American Psychiatric Association, 4
27.
go back to reference Schopler E, Reichler RJ, Renner BR: The Childhood Autism Rating Scale (CARS), for Diagnostic Screening and Classification in Autism. 1986, New York, NY: Irvington Schopler E, Reichler RJ, Renner BR: The Childhood Autism Rating Scale (CARS), for Diagnostic Screening and Classification in Autism. 1986, New York, NY: Irvington
28.
go back to reference Enstrom AM, Van de Water JA, Ashwood P: Autoimmunity in autism. Curr Opin Investig Drugs. 2009, 10 (5): 463-73.PubMed Enstrom AM, Van de Water JA, Ashwood P: Autoimmunity in autism. Curr Opin Investig Drugs. 2009, 10 (5): 463-73.PubMed
29.
go back to reference Zhang B, Angelidou A, Alysandratos KD, Vasiadi M, Francis K, Asadi S, et al: Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children. J Neuroinflammation. 2010, 7: 80-10.1186/1742-2094-7-80.PubMedCentralCrossRefPubMed Zhang B, Angelidou A, Alysandratos KD, Vasiadi M, Francis K, Asadi S, et al: Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children. J Neuroinflammation. 2010, 7: 80-10.1186/1742-2094-7-80.PubMedCentralCrossRefPubMed
30.
go back to reference Galaezzi M, Annunziata P, Sebastiani GD, Bellisai F: Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological and HLA class II gene association. European Connected Action on the Immunogenetics of SLE. J Rheumatol. 2000, 27 (1): 135-141. Galaezzi M, Annunziata P, Sebastiani GD, Bellisai F: Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological and HLA class II gene association. European Connected Action on the Immunogenetics of SLE. J Rheumatol. 2000, 27 (1): 135-141.
31.
go back to reference Jyonouchi H, Sun S, Itokazu N: Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorders. Neuropsychobiology. 2002, 46 (2): 76-84. 10.1159/000065416.CrossRefPubMed Jyonouchi H, Sun S, Itokazu N: Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorders. Neuropsychobiology. 2002, 46 (2): 76-84. 10.1159/000065416.CrossRefPubMed
32.
go back to reference Mutter J, Naumann J, Schneider R, Walach H, Haley B: Mercury and autism: accelerating evidence?. Neuro Endocrinol Lett. 2005, 26 (5): 439-446.PubMed Mutter J, Naumann J, Schneider R, Walach H, Haley B: Mercury and autism: accelerating evidence?. Neuro Endocrinol Lett. 2005, 26 (5): 439-446.PubMed
33.
go back to reference Dochniak MJ: Autism spectrum disorders: Exogenous protein insult. Med Hypotheses. 2007, 89: 545-549.CrossRef Dochniak MJ: Autism spectrum disorders: Exogenous protein insult. Med Hypotheses. 2007, 89: 545-549.CrossRef
34.
go back to reference 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 form milk, Chlamydia pneumoniae and Streptococcus group A. J Neuroimmunol. 2002, 129 (1-2): 168-177. 10.1016/S0165-5728(02)00180-7.CrossRefPubMed 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 form milk, Chlamydia pneumoniae and Streptococcus group A. J Neuroimmunol. 2002, 129 (1-2): 168-177. 10.1016/S0165-5728(02)00180-7.CrossRefPubMed
35.
go back to reference 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): e420-10.1542/peds.112.5.e420.CrossRefPubMed 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): e420-10.1542/peds.112.5.e420.CrossRefPubMed
36.
go back to reference Steck AJ, Stalder AK, Renaud S: Anti-myelin-associated glycoprotein neuropathy. Curr Opin Neurol. 2006, 19 (5): 458-463. 10.1097/01.wco.0000245368.36576.0d.CrossRefPubMed Steck AJ, Stalder AK, Renaud S: Anti-myelin-associated glycoprotein neuropathy. Curr Opin Neurol. 2006, 19 (5): 458-463. 10.1097/01.wco.0000245368.36576.0d.CrossRefPubMed
37.
go back to reference Renaud S, Fuhr P, Gregor M, Schweikert K, Lorenz D, Daniels C, et al: High-dose rituximab and anti-MAG associated polyneuropathy. Neurology. 2006, 66 (5): 742-744. 10.1212/01.wnl.0000201193.00382.b3.CrossRefPubMed Renaud S, Fuhr P, Gregor M, Schweikert K, Lorenz D, Daniels C, et al: High-dose rituximab and anti-MAG associated polyneuropathy. Neurology. 2006, 66 (5): 742-744. 10.1212/01.wnl.0000201193.00382.b3.CrossRefPubMed
38.
go back to reference Benedetti L, Briani C, Grandis M, Vigo T, Gobbi M, Ghiglione E, et al: Predictors of response to rituximab in patients with neuropathy and anti-myelin associated glycoprotein immunoglobulin M. J Peripher Nerv Syst. 2007, 12 (2): 102-107. 10.1111/j.1529-8027.2007.00129.x.CrossRefPubMed Benedetti L, Briani C, Grandis M, Vigo T, Gobbi M, Ghiglione E, et al: Predictors of response to rituximab in patients with neuropathy and anti-myelin associated glycoprotein immunoglobulin M. J Peripher Nerv Syst. 2007, 12 (2): 102-107. 10.1111/j.1529-8027.2007.00129.x.CrossRefPubMed
Metadata
Title
Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity
Authors
Gehan A Mostafa
Laila Y AL-ayadhi
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-39

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