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Altered Immune Function In Autism

Published online by Cambridge University Press:  07 November 2014

Gina Delgiudice-Asch  and
Eric Hollander
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Abstract

Recent studies of the pathogenesis of autism have suggested that this disorder may have an autoimmune basis in some patients. Observations have been made regarding cellular and humoral immune dysfunction, abnormalities associated with the complement system and major histocompatibility complex gene expression, differences in soluble mediators of the immune response, and the presence of antibrain and antimyelin autoantibodies. In this article, we review these experimental and clinical observations, and examine preliminary efforts using immunomodulatory therapies to treat autism.

Type
Feature Article
Information
CNS Spectrums , Volume 2 , Issue 5: Autism: Neuropsychiatric Developments , May 1997 , pp. 61 - 68
Copyright
Copyright © Cambridge University Press 1997

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References

1.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:66–71.Google Scholar
2.Kanner, L. Autistic disturbances of affective contact. Nerv. Child. 1943;2:217–250.Google Scholar
3.Asperger, H. Die autistischen psychopathen in kindersalter. Archiv fur Psychiatrie und Nervenkrankheiten. 1944;117:76–136.Google Scholar
4.Volkmar, FR, Klin, A, Siegal, B, et al. Field trial for autistic disorder in DSM-IV. Am J Psychiatry. 1994;151:1361–1367.Google Scholar
5.Cook, E, Leventhal, B. Autistic disorders and other pervasive developmental disorders. Psychiatr Clin North Am. 1995;4:381–399.Google Scholar
6.Singh, VK, Fudenberg, HH, Emerson, D, Coleman, M. Immunodiagnosis and immunotherapy in autistic children. Ann NY Acad Sci. 1988;540:602–604.Google Scholar
7.Singh, VK, Warren, RP, Odell, JD, Cole, P. Changes of soluble IL-2,IL-2R, T8 antigen and IL-1 in the serum of autistic children. Clin Immunol Immunopathol. 1991;61:448–455.Google Scholar
8.Singh, VK, Warren, RP, Odell, JD, Warren, WL, Cole, P. Antibodies to myelin basic protein in children with autistic behavior. Brain Behav Immun. 1993;7:97–103.Google Scholar
9.Warren, RP, Foster, A, Margaretten, NC, Pace, NC. Immune abnormalities in patients with autism. J Autism Dev Disord. 1986;16:189–197.Google Scholar
10.Warren, RP, Foster, A, Margaretten, NC. Reduced natural killer cell activity in autism. J Am Acad Child Adolesc Psychiatry. 1987;26:333–335.Google Scholar
11.Warren, RP, Singh, VK, Cole, P, et al. Increased frequency of the null allele at the complement C4B locus in autism. Clin Exp Immunol. 1991;83:438–440.Google Scholar
12.Warren, RP, Yonk, LJ, Burger, RA, et al. Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism. Immunol Invest. 1990;19:245–251.Google Scholar
13.Weizman, A, Weizman, R, Szekely, GA, Wijsenbeek, H, Livini, E. Abnormal immune response to brain tissue antigen in the syndrome of autism. Am J Psychiatry. 1982;7:1462–1465.Google Scholar
14.Yonk, LJ, Warren, RP, Burger, RA, et al. CD 4 and helper T cell depression in autism. Immunol Lett. 1990;25:341–346.Google Scholar
15.Gupta, S, Aggarwal, S, Heads, C. Brief report: dysregulated immune system in children with autism; beneficial effects of intravenous immune globulin on autistic characteristics. J Autism Dev Disord. 1996;26:439–452.Google Scholar
16.Zimmerman, A, Frye, VH, Potter, NT. Immunological aspects of autism. Internat J Ped. 1993;8:199–204.Google Scholar
17.Money, J, Bobrow, NA, Clarke, FC, et al. Autism and autoimmune disease: a family study. J Autism Child Schizophr. 1971;1:146–160.Google Scholar
18.Chess, S. Autism in children with congential rubella. J Autism Child Schizophr. 1971;1:33–47.Google Scholar
19.Desmond, MM, Wilson, GS, Melnick, JL, et al. Congenital rubella encephalitis — course and early sequelae. J Pediatr. 1967;71:311–331.Google Scholar
20.Knobloch, H, Pasamanick, B. Gesell and Amatruda's Developmental Diagnosis. 3rd ed. New York, NY: Harper & Row; 1974:320–339.Google Scholar
21.Stubbs, EG, Ash, E, Williams, CPS. Autistic and congenital cytomegalovirus. J Autism Dev Disord. 1984;14:183–189.Google Scholar
22.Peterson, MR, Torrey, EF. Viruses and other infectious agents as behavioral teratogens. In: Coleman, M, ed. The Autistic Syndromes. New York, NY: American Elsevier; 1976:23–42.Google Scholar
23.Stubbs, EG. Autistic children exhibit undetectable hemagglutination-inhibition antibody titers despite previous rubella vaccination. J Autism Child Schizophr. 1976;6:269–274.Google Scholar
24.Sells, CJ, Carpenter, RL, Ray, CG. Sequelae of central nervous system enterovirus infection. N Engl J Med. 1975;293:1–4.Google Scholar
25.Deykin, EY, MacMahon, B. Viral exposure and autism. Am J Epidemiol. 1979;109:628–638.Google Scholar
26.Roitt, I. Essential Immunology. Oxford, England: Blackwell Scientific Publications; 1991:28–29,32,129–139,325–329.Google Scholar
27.Stubbs, EG, Crawford, ML. Depressed lymphocyte responsiveness in autistic children. J Autism Child Schizophr. 1977;7:49–55.Google Scholar
28.Ferrari, P, Marescot, M, Moulias, R, et al. Et at immunitaire dans l'autisme infantile. Encephale. 1988;14:339–344.Google Scholar
29.Plioplys, AV, Greaves, A, Kazemi, K, Silverman, E. Lymphocyte function in autism and Rett syndrome. Neuropsychobiology. 1994;7:12–16.Google Scholar
30.Morimoto, C, Hafler, DA, Weiner, HL, et al. Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. N Engl J Med. 1987;316:67–72.Google Scholar
31.Denney, DR, Frei, BW, Gaffney, GR. Lymphocyte subsets and interleukin-2 receptors in autistic children. J Autism Dev Disord. 1996;26:87–97.Google Scholar
32.Goto, M, Tanimoto, K, Chihara, T, Horiuchi, Y. Natural killer cell mediated cytotoxicity in Sjogren's syndrome and rheumatoid arthritis. Arthritis Rheum. 1981;24:1377–1382.Google Scholar
33.Goto, M, Tanimoto, K, Horiuchi, Y. Natural killer cell mediated cytotoxicity in systemic lupus erythematosus. Arthritis Rheum. 1980;23:1274–1281.Google Scholar
34.Walisman, BH. Current trends in multiple sclerosis research. Immunol Today. 1981;2:87–93.Google Scholar
35.Ritvo, ER, Yuwiler, A, Geller, E, Ornitz, EM, Saeger, K, Plotkin, S. Increased blood serotonin and platelets in early infantile autism. Arch Gen Psychiatry. 1970;42:129–133.Google Scholar
36.Wright, HH, Abramson, RK, Self, S, Genco, P, Cuccaro, M. Serotonin may affect lymphocyte cell surface markers in autistic probands. Presented at the American Academy of Child and Adolescent Psychiatry; 1990; San Francisco, Calif. NR Abstract 12.Google Scholar
37.Dawson, CA, Lineham, JH. Biogenic amines. In: Lenfant, C, Masarro, D, eds. Lung Biology in Health and Disease, Lung Cell Biology. Vol. 41. New York, NY: Marcel Dekker; 1989:1091.Google Scholar
38.Jackson, JC, Cross, RJ, Walker, F, Markesbery, WR, Brooks, WH, Roszman, TL. Influence of serotonin on the immune responses. Immunology. 1985;54:505.Google Scholar
39.Laberge, S, Cruikshank, WW, Beer, DJ, Center, DM. Secretion of IL-6 from serotonin-stimulated CD8+ T cells in vitro. J Immunol. 1996:156:310–315.Google Scholar
40.Husby, G, van de Rijn, I, Zabriskie, JB, Abdin, ZH, Williams, RC Jr. Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J Exp Med. 1976;144:1094–1110.Google Scholar
41.Plioplys, AV, Greaves, A, Yoshida, W. Anti-CNS antibodies in childhood neurologic diseases. Neuropediatrics. 1989;20:92–102.Google Scholar
42.Todd, RD, Ciaranello, RD. Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child. Proc Natl head Sci USA. 1985;82:612–616.Google Scholar
43.Yuwiler, A, Shih, JS, Chen, CH, et al. Hyperserotoninemia and antiserotonin antibodies in autism and other disorders. J Autism Dev Disord. 1992;22:33–45.Google Scholar
44.Cook, EH, Perry, BD, Dawson, G, Wainwright, MS, Leventhal, BL, et al. Receptor inhibition by immunoglobulins: specific inhibition by autistic children, their relatives, and control subjects. J Autism Dev Disord. 1993;23:67–78.Google Scholar
45.Warren, RP, Cole, P, Odell, JD, et al. Detection of maternal antibodies in infantile autism. J Am Acad Child Adolesc Psychiatry. 1990;29:873–877.Google Scholar
46.Gillberg, IC, Gillberg, C, Kopp, , et al. Hypothyroidism and autism spectrum disorders. J Child Psychol Psychiatiatry. 1992;33:531–542.Google Scholar
47.Plioplys, AV, Greaves, , Kazemi, K, Silverman, E. Autism: anti-210K neurofilament immunoglobulin reactivity. Neurology. 1989;39(suppl 1):187.Google Scholar
48.Bauman, ML, Kemper, TL. Limbic and cerebellar abnormalities: consistent findings in infantile autism. J Neuropathol Exp Neurol. 1988;47:369.Google Scholar
49.ML, Bauman. Microscopic neuroanatomic abnormalities in autism. Pediatrics. 1991;87:791–796.Google Scholar
50.Todd, JA, Acha-Orbea, H, Bell, JT, et al. A molecular basis for MHC Class II-associated autoimmunity. Science. 1988;240:1003–1009.Google Scholar
51.Stubbs, EG, Ritvo, ER, Mason-Brothers, A. Autism and shared parental HLA antigens. J Am Acad Child Adolesc Psychiatry. 1985;24:182–185.Google Scholar
52.Taylor, C, Faulk, WP. Prevention of recurrent abortions with leukocyte transfusion. Lancet. 1981;2:68–70.Google Scholar
53.Redman, CWG. Immunological aspects of eclampsia and pre-eclampsia. In: Hearn, JP, ed. Immunological Aspects of Reproduction and Fertility Control. Lancaster, UK: MTP Press; 1980:52–55.Google Scholar
54.Warren, RP, Singh, VK, Cole, P, et al. Possible association of the extended MHC haplotype B44-SC30-DR4 with autism. Immunogenetics. 1992;36:203–207.Google Scholar
55.Warren, RP, Odell, JD, Warren, WL, et al. Brief report: immunoglobulin A deficiency in a subset of autistic subjects. J Autism Dev Disord. 1997;27:187–192.Google Scholar
56.Moreno, H, Brijas, L, Arrilta, A, et al. Heterogeneidad clinica del sindrome autista: un estudio en sesenta familias. Invest Clin. 1992;33:13–31.Google Scholar
57.Suzuki, M, Nakazima, K, Sugiyama, A, Nakashita, Y, Ogawa, T, et al. On the effects of pentoxifylline upon the EEG activity of early infantile autism: quantitative pharmaco-electroen-cephalographic study. Brain Dev. 1984;6:156.Google Scholar
58.Selman, K, Reine, CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988;23:339–346.Google Scholar
59.Brosnan, CF, Selmaj, K, Raines, CS. Hypothesis: a role for TNF in immune-mediated demyelination and its relevance to multiple sclerosis. J Neuroimmunol. 1988;18:87–94.Google Scholar
60.Natal, S, Louboutin, JP, Chabannes, D, et al. Pentoxifylline inhibits experimental allergic encephalitis. Acta Neurol Scand. 1993;88:97–99.Google Scholar
61.Black, RS, Barclay, LL, Nolan, KA. Pentoxifylline in cerebrovascular dementia. J Am Geriatr Soc. 1992;40:237–244.Google Scholar
62.Sogame, S. On our experience in using pentoxifylline for abnormal behavior and the autistic syndrome. Japanese Journal of Child Psychiatry. 1978;19:134–144.Google Scholar
63.Nakane, A. Effect of pentoxifylline on autistic children. Tokyoto Eisei Gakkashi. 1980;64:104–105.Google Scholar
64.Shimoide, M. Effect of pentoxifylline on infantile autism. Clin Exp Med. 1981;58:285–288.Google Scholar
65.Turek, S. Treatment of psychotic and autistic children with pentoxifylline. ASANA. 1981;1:51–60.Google Scholar
66.Dwyer, JM. Manipulating the immune system with immunoglobulin. N Engl J Med. 1992;326:4104–4109.Google Scholar
67.Nevsimalova, S, Tauberova, A, Doutlik, S, Kucera, V, Dlouha, O. A role for autoimmunity in the etiopathogenesis of Landau-Kleffner Syndrome? Brain Dev. 1992;14:342–345.Google Scholar
68.Cole, AJ, Andermann, F, Taylor, L, et al. The Landau-Kleffner syndrome of acquired epileptic aphasia: unusual clinical outcome, surgical experience, and absence of encephalitis. Neurology. 1988;38:31–38.Google Scholar
69.Tuchman, RF. Epilepsy, language and behavior: clinical models in childhood. J Child Neurol. 1994;9:95–102.Google Scholar
70.Paquier, PF, Van Dongen, HR, Loonen, CB. The Landau-Kleffner syndrome or acquired aphasia with convusive disorder. Arch Neurol. 1992;49:354–359.Google Scholar