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

Journal of Neuroinflammation

Laila Y AL-ayadhi²  Gehan A Mostafa¹ 

[1] Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt;Autism Research and Treatment Center, AL-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia

关键词: Childhood Autism Rating Scale;    autoimmunity;    autism;    anti-ganglioside antibodies;   

Others  :  1213357
DOI  :  10.1186/1742-2094-8-39

 received in 2011-02-24, accepted in 2011-04-25,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Mostafa and AL-ayadhi; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Dalton R, Forman MA, Boris NW: Pervasive developmental disorders and childhood psychosis. In Nelson textbook of Pediatrics. 17th edition. Edited by Behrman RE, Kliegman RM, Jenson HB. Philadelphia: WB Saunders; 2004:93-94.
• [2]Cohly HH, Panja A: Immunological findings in autism. Int Rev Neurobiol 2005, 71:317-341.
• [3]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.
• [4]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.
• [5]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.
• [6]Mostafa GA, Kitchener N: Serum anti-nuclear antibodies as a marker of autoimmunity in Egyptian autistic children. Pediatr Neurol 2009, 40:107-112.
• [7]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.
• [8]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.
• [9]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]Torres AR, Maciulis A, Odell D: The association of MHC genes with autism. Front Biosci 2001, 6:936-943.
• [11]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.
• [12]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.
• [13]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.
• [14]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.
• [15]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.
• [16]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.
• [17]Kato T, Hatanaka K: Purification of gangliosides by liquid-liquid partitionchromatography. J Lipid Res 2008, 49(11):2474-2478.
• [18]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.
• [19]Ribeiro CM, Vasconcelos BC, Silva Neto JC, Silva VA Júnior, Figueiredo NG: Histopathological analysis of gangliosides use in peripheral nerve regeneration after axonotmesis in rats. Acta Cir Bras 2008, 23(4):364-371.
• [20]Plomp JJ, Willison HJ: Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction. J Physiol 2009, 587(Pt 16):3979-3999.
• [21]Ravindranath MH, Muthugounder S, Saravanan TS, Presser N, Morton DL: Human antiganglioside antibodies: validation of ELISA. Ann NY Acad Sci 2005, 1050:229-242.
• [22]Watanabe O, Arimura K: Pathomechanism of autoantibody production inneurological disorders. Nippon Rinsho 2008, 66(6):1065-1072.
• [23]Greenwood DL, Gitlits VM, Alderuccio F, Sentry JW, Toh BH: Autoantibodies in neuropsychiatric lupus. Autoimmunity 2002, 35(2):79-86.
• [24]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.
• [25]Kusunoki S, Kaida K: Antibodies against ganglioside complexes in Guillain-Barré syndrome and related disorders. J Neurochem 2011, 116(5):828-832.
• [26]American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th edition. Washington DC: American Psychiatric Association; 1994.
• [27]Schopler E, Reichler RJ, Renner BR: The Childhood Autism Rating Scale (CARS), for Diagnostic Screening and Classification in Autism. New York, NY: Irvington; 1986.
• [28]Enstrom AM, Van de Water JA, Ashwood P: Autoimmunity in autism. Curr Opin Investig Drugs 2009, 10(5):463-73.
• [29]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. BioMed Central Full Text
• [30]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]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.
• [32]Mutter J, Naumann J, Schneider R, Walach H, Haley B: Mercury and autism: accelerating evidence? Neuro Endocrinol Lett 2005, 26(5):439-446.
• [33]Dochniak MJ: Autism spectrum disorders: Exogenous protein insult. Med Hypotheses 2007, 89:545-549.
• [34]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.
• [35]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.
• [36]Steck AJ, Stalder AK, Renaud S: Anti-myelin-associated glycoprotein neuropathy. Curr Opin Neurol 2006, 19(5):458-463.
• [37]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.
• [38]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.