Skip to main content
SpringerLink
Log in

Molecular Mimicry: Anti-DNA Antibodies Bind Microbial and Nonnucleic Acid Self-Antigens

  • Chapter
Molecular Mimicry: Infection-Inducing Autoimmune Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 296))

Abstract

Although cells of the innate immune response have a variety of pattern recognition receptors that are triggered by blood classes of markers, a critical feature of the adaptive immune response is antigenic specificity. Yet it is becoming increasingly clear that the specificity of lymphocyte receptors admits of some laxity. Cross-reactivity may, in fact, be necessary for lymphocyte survival as antigen receptor signaling maintains cellular viability in the absence of antigen activation. Studies of molecular mimicry have revealed many instances in which antibodies to microbial antigens bind also to self-antigens; in some cases, this cross-reactivity has pathogenic potential. In this chapter, we describe cross-reactivity between two self-antigens, DNA and NMDA receptors, and how antibodies with specificity for DNA in patients with splenic lupus may cause central nervous system damage by virtue of binding also to neuronal receptors. This example serves as a reminder that cross-reactivity may exist among self-antigens as well as between foreign and self-antigens.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Aarli, JA (2000) Epilepsy and the immune system. Arch Neurol 57, 1689–92

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Rahman, A, Shetty, AK, Abou-Donia, MB (2002) Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome. Neurobiol Dis 10, 306–26

    Article  PubMed  CAS  Google Scholar 

  • Akbarian, S, Sucher, NJ, Bradley, D, Tafazzoli, A, Trinh, D, Hetrick, WP, Potkin, SG, Sandman, CA, Bunney, WE, Jr., Jones, EG (1996) Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 16, 19–30

    PubMed  CAS  Google Scholar 

  • Ang, CW, Jacobs, BC, Laman, JD (2004) The Guillain-Barre syndrome: a true case of molecular mimicry. Trends Immunol 25, 61–6

    PubMed  CAS  Google Scholar 

  • Avenet, P, Leonardon, J, Besnard, F, Graham, D, Depoortere, H, Scatton, B (1997) Antagonist properties of eliprodil and other NMDA receptor antagonists at rat NR1A/NR2A and NR1A/NR2B receptors expressed in Xenopus oocytes. Neurosci Lett 223, 133–6

    Article  PubMed  CAS  Google Scholar 

  • Ballok, DA, Woulfe, J, Sur, M, Cyr, M, Sakic, B (2004a) Hippocampal damage in mouse and human forms of systemic autoimmune disease. Hippocampus 14, 649–61

    Article  PubMed  Google Scholar 

  • Ballok, DA, Earls, AM, Krasnik, C, Hoffman, SA, Sakic, B (2004b) Autoimmune-induced damage of the midbrain dopaminergic system in lupus-prone mice. J Neuroimmunol 152, 83–97

    Article  PubMed  CAS  Google Scholar 

  • Banks, WA (2001) Enhanced leptin transport across the blood-brain barrier by alpha 1-adrenergic agents. Brain Res 899, 209–17

    Article  PubMed  CAS  Google Scholar 

  • Brey, RL, Holliday, SL, Saklad, AR, Navarrete, MG, Hermosillo-Romo, D, Stallworth, CL, Valdez, CR, Escalante, A, del Rincon, I, Gronseth, G, Rhine, CB, Padilla, P, McGlasson, D (2002) Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology 58, 1214–20

    PubMed  CAS  Google Scholar 

  • Cavill, D, Waterman, SA, Gordon, TP (2004) Antibodies raised against the second extracellular loop of the human muscarinic M3 receptor mimic functional autoantibodies in Sjogren’s syndrome. Scand J Immunol 59, 261–6

    Article  PubMed  CAS  Google Scholar 

  • Cervera, R, Asherson, RA, Font, J, Tikly, M, Pallares, L, Chamorro, A, Ingelmo, M (1997) Chorea in the antiphospholipid syndrome. Clinical, radiologic, and immunologic characteristics of 50 patients from our clinics and the recent literature. Medicine (Baltimore) 76, 203–12

    Article  PubMed  CAS  Google Scholar 

  • Choi, DW, Rothman, SM (1990) The role of glutamate neurotoxicity in hypoxicischemic neuronal death. Annu Rev Neurosci 13, 171–82

    Article  PubMed  CAS  Google Scholar 

  • Danysz, W, Parsons, CG (2003) The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: preclinical evidence. Int J Geriatr Psychiatry 18, S23–32

    PubMed  Google Scholar 

  • DeGiorgio, LA, Konstantinov, KN, Lee, SC, Hardin, JA, Volpe, BT, Diamond, B (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 7, 1189–93

    Article  PubMed  CAS  Google Scholar 

  • Denburg, SD, Denburg, JA (1999) Cognitive dysfunction in systemic lupus erythematosus. In Systemic Lupus Erythematosus (R. G. Lahita, ed.), pp. 611–629. Academic Press, San Diego

    Google Scholar 

  • Deocharan, B, Qing, X, Lichauco, J, Putterman, C (2002) Alpha-actinin is a cross-reactive renal target for pathogenic anti-DNA antibodies. J Immunol 168, 3072–8

    PubMed  CAS  Google Scholar 

  • Diamond, B, Scharff, MD (1984) Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity. Proc Natl Acad Sci U S A 81, 5841–4

    PubMed  CAS  Google Scholar 

  • Esposito, P, Chandler, N, Kandere, K, Basu, S, Jacobson, S, Connolly, R, Tutor, D, Theoharides, TC (2002) Corticotropin-releasing hormone and brain mast cells regulate blood-brain-barrier permeability induced by acute stress. J Pharmacol Exp Ther 303, 1061–6

    Article  PubMed  CAS  Google Scholar 

  • Faaber, P, Rijke, TP, van de Putte, LB, Capel, PJ, Berden, JH (1986) Cross-reactivity of human and murine anti-DNA antibodies with heparan sulfate. The major glycosaminoglycan in glomerular basement membranes. J Clin Invest 77, 1824–30

    PubMed  CAS  Google Scholar 

  • Fessel, WJ (1962) Autoimmunity and mental illness. A preliminary report. Arch Gen Psychiatry 6, 320–3

    PubMed  CAS  Google Scholar 

  • Friedman, A, Kaufer, D, Shemer, J, Hendler, I, Soreq, H, Tur-Kaspa, I (1996) Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response. Nat Med 2, 1382–5

    Article  PubMed  CAS  Google Scholar 

  • Gaynor, B, Putterman, C, Valadon, P, Spatz, L, Scharff, MD, Diamond, B (1997) Peptide inhibition of glomerular deposition of an anti-DNA antibody. Proc Natl Acad Sci U S A 94, 1955–60

    Article  PubMed  CAS  Google Scholar 

  • Heresco-Levy, U, Javitt, DC (1998) The role ofN-methyl-d-aspartate (NMDA) receptor-mediated neurotransmission in the pathophysiology and therapeutics of psychiatric syndromes. Eur Neuropsychopharmacol 8, 141–52

    Article  PubMed  CAS  Google Scholar 

  • Hetherington, H, Kuzniecky, R, Pan, J, Mason, G, Morawetz, R, Harris, C, Faught, E, Vaughan, T, Pohost, G (1995) Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T. Ann Neurol 38, 396–404

    Article  PubMed  CAS  Google Scholar 

  • Hugg, JW, Laxer, KD, Matson, GB, Maudsley, AA, Weiner, MW (1993) Neuron loss localizes human temporal lobe epilepsy by in vivo proton magnetic resonance spectroscopic imaging. Ann Neurol 34, 788–94

    Article  PubMed  CAS  Google Scholar 

  • Kalume, F, Lee, SM, Morcos, Y, Callaway, JC, Levin, MC (2004) Molecular mimicry: cross-reactive antibodies from patients with immune-mediated neurologic disease inhibit neuronal firing. J Neurosci Res 77, 82–9

    Article  PubMed  CAS  Google Scholar 

  • Kier, AB (1990) Clinical neurology and brain histopathology in NZB/NZW F1 lupus mice. J Comp Pathol 102, 165–77

    PubMed  CAS  Google Scholar 

  • Kim, YI, Neher, E (1988) IgG from patients with Lambert-Eaton syndrome blocks voltage-dependent calcium channels. Science 239, 405–8

    PubMed  CAS  Google Scholar 

  • Kirvan, CA, Swedo, SE, Heuser, JS, Cunningham, MW (2003) Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med 9, 914–20

    Article  PubMed  CAS  Google Scholar 

  • Kosinski, CM, Standaert, DG, Counihan, TJ, Scherzer, CR, Kerner, JA, Daggett, LP, Velicelebi, G, Penney, JB, Young, AB, Landwehrmeyer, GB (1998) Expression of N-methyl-d-aspartate receptor subunit mRNAs in the human brain: striatum and globus pallidus. J Comp Neurol 390, 63–74

    Article  PubMed  CAS  Google Scholar 

  • Kowal, C, Diamond, B (2004) Unpublished observations

    Google Scholar 

  • Kowal, C, DeGiorgio, LA, Nakaoka, T, Hetherington, H, Huerta, PT, Diamond, B, Volpe, BT (2004) Cognition and immunity; antibody impairs memory. Immunity 21, 179–88

    Article  PubMed  CAS  Google Scholar 

  • Kozora, E, Thompson, LL, West, SG, Kotzin, BL (1996) Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients without overt central nervous system disease. Arthritis Rheum 39, 2035–45

    PubMed  CAS  Google Scholar 

  • Kuppenbender, KD, Standaert, DG, Feuerstein, TJ, Penney, JB, Jr., Young, AB, Landwehrmeyer, GB (2000) Expression of NMDA receptor subunit mRNAs in neurochemically identified projection and interneurons in the human striatum. J Comp Neurol 419, 407–21

    PubMed  CAS  Google Scholar 

  • Leveque, C, Hoshino, T, David, P, Shoji-Kasai, Y, Leys, K, Omori, A, Lang, B, el Far, O, Sato, K, Martin-Moutot, N, et al (1992) The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen. Proc Natl Acad Sci U S A 89, 3625–9

    PubMed  CAS  Google Scholar 

  • Licht, R, Dieker, JW, Jacobs, CW, Tax, WJ, Berden, JH (2004) Decreased phagocytosis of apoptotic cells in diseased SLE mice. J Autoimmun 22, 139–45

    Article  PubMed  CAS  Google Scholar 

  • Marino, MJ, Conn, PJ (2002) Direct and indirect modulation of the N-methyl-D-aspartate receptor. Curr Drug Targets CNS Neurol Disord 1, 1–16

    PubMed  CAS  Google Scholar 

  • Martin, R, Gran, B, Zhao, Y, Markovic-Plese, S, Bielekova, B, Marques, A, Sung, MH, Hemmer, B, Simon, R, McFarland, HF, Pinilla, C (2001) Molecular mimicry and antigen-specific T cell responses in multiple sclerosis and chronic CNS Lyme disease. J Autoimmun 16, 187–92

    Article  PubMed  CAS  Google Scholar 

  • Mattson, MP, LaFerla, FM, Chan, SL, Leissring, MA, Shepel, PN, Geiger, JD (2000) Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders. Trends Neurosci 23, 222–9

    PubMed  CAS  Google Scholar 

  • Morris, RG, Anderson, E, Lynch, GS, Baudry, M(1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319, 774–6

    PubMed  CAS  Google Scholar 

  • Oztas, B (1998) Sex and blood-brain barrier. Pharmacol Res 37, 165–7

    PubMed  CAS  Google Scholar 

  • Oztas, B, Akgul, S, Arslan, FB (2004) Influence of surgical pain stress on the blood-brain barrier permeability in rats. Life Sci 74, 1973–9

    PubMed  CAS  Google Scholar 

  • Pardridge, W (1998) Introduction to the Blood-Brain Barrier: Methodology, Biology, and Pathology (W. Pardridge, ed.) Cambridge University Press, Cambridge

    Google Scholar 

  • Paul, R, Lorenzl, S, Koedel, U, Sporer, B, Vogel, U, Frosch, M, Pfister, HW (1998) Matrix metalloproteinases contribute to the blood-brain barrier disruption during bacterial meningitis. Ann Neurol 44, 592–600

    Article  PubMed  CAS  Google Scholar 

  • Potter, PK, Cortes-Hernandez, J, Quartier, P, Botto, M, Walport, MJ (2003) Lupus-prone mice have an abnormal response to thioglycolate and an impaired clearance of apoptotic cells. J Immunol 170, 3223–32

    PubMed  CAS  Google Scholar 

  • Putterman, C, Diamond, B (1998) Immunization with a peptide surrogate for double-stranded DNA (dsDNA) induces autoantibody production and renal immunoglobulin deposition. J Exp Med 188, 29–38

    Article  PubMed  CAS  Google Scholar 

  • Ring, A, Weiser, JN, Tuomanen, EI (1998) Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway. J Clin Invest 102, 347–60

    Article  PubMed  CAS  Google Scholar 

  • Rutter, JV, Jehanli, A, Harrison, R, Lunt, GG (1987) Immunological factors in neuronal degeneration with particular reference to motor neurone disease. Gerontology 33, 187–92

    Article  PubMed  CAS  Google Scholar 

  • Rutter, M, Schopler, E (1987) Autism and pervasive developmental disorders: concepts and diagnostic issues. J Autism Dev Disord 17, 159–86

    Article  PubMed  CAS  Google Scholar 

  • Sabbaga, J, Line, SR, Potocnjak, P, Madaio, MP (1989) A murine nephritogenic monoclonal anti-DNA autoantibody binds directly to mouse laminin, the major non-collagenous protein component of the glomerular basement membrane. Eur J Immunol 19, 137–43

    PubMed  CAS  Google Scholar 

  • Sakic, B, Szechtman, H, Keffer, M, Talangbayan, H, Stead, R, Denburg, JA (1992) A behavioral profile of autoimmune lupus-prone MRL mice. Brain Behav Immun 6, 265–85

    PubMed  CAS  Google Scholar 

  • Sakic, B, Kolb, B, Whishaw, IQ, Gorny, G, Szechtman, H, Denburg, JA (2000) Immunosuppression prevents neuronal atrophy in lupus-prone mice: evidence for brain damage induced by autoimmune disease? J Neuroimmunol 111, 93–101

    Article  PubMed  CAS  Google Scholar 

  • Sastre-Garriga, J, Montalban, X (2003) APS and the brain. Lupus 12, 877–82

    Article  PubMed  CAS  Google Scholar 

  • Scherzer, CR, Landwehrmeyer, GB, Kerner, JA, Counihan, TJ, Kosinski, CM, Standaert, DG, Daggett, LP, Velicelebi, G, Penney, JB, Young, AB (1998) Expression of Nmethyl-D-aspartate receptor subunit mRNAs in the human brain: hippocampus and cortex. J Comp Neurol 390, 75–90

    Article  PubMed  CAS  Google Scholar 

  • Schutzer, SE, Brunner, M, Fillit, HM, Berger, JR (2003) Autoimmune markers in HIV-associated dementia. J Neuroimmunol 138, 156–61

    Article  PubMed  CAS  Google Scholar 

  • Sherman, GF, Morrison, L, Rosen, GD, Behan, PO, Galaburda, AM (1990) Brain abnormalities in immune defective mice. Brain Res 532, 25–33

    PubMed  CAS  Google Scholar 

  • Sinha, S, Newsom-Davis, J, Mills, K, Byrne, N, Lang, B, Vincent, A (1991) Autoimmune aetiology for acquired neuromyotonia (Isaacs’ syndrome) Lancet 338, 75–7

    Article  PubMed  CAS  Google Scholar 

  • Staines, DR (2004a) Is fibromyalgia an autoimmune disorder of endogenous vasoactive neuropeptides? Med Hypotheses 62, 665–9

    PubMed  CAS  Google Scholar 

  • Staines, DR (2004b) Is Gulf War Syndrome an autoimmune disorder of endogenous neuropeptides, exogenous sandfly maxadilan and molecular mimicry? Med Hypotheses 62, 658–64

    PubMed  CAS  Google Scholar 

  • Staines, DR (2004c) Is sudden infant death syndrome (SIDS) an autoimmune disorder of endogenous vasoactive neuropeptides? Med Hypotheses 62, 653–7

    PubMed  CAS  Google Scholar 

  • Standaert, DG, Testa, CM, Young, AB, Penney, JB, Jr (1994) Organization of N-methyl-D-aspartate glutamate receptor gene expression in the basal ganglia of the rat. J Comp Neurol 343, 1–16

    Article  PubMed  CAS  Google Scholar 

  • Stein, CM, Olson, JM, Gray-McGuire, C, Bruner, GR, Harley, JB, Moser, KL (2002) Increased prevalence of renal disease in systemic lupus erythematosus families with affected male relatives. Arthritis Rheum 46, 428–35

    Article  PubMed  Google Scholar 

  • Szechtman, H, Sakic, B, Denburg, JA (1997) Behaviour of MRL mice: an animal model of disturbed behaviour in systemic autoimmune disease. Lupus 6, 223–9

    PubMed  CAS  Google Scholar 

  • Tanaka, S, Kuratsune, H, Hidaka, Y, Hakariya, Y, Tatsumi, KI, Takano, T, Kanakura, Y, Amino, N (2003) Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med 12, 225–30

    PubMed  CAS  Google Scholar 

  • Trivedi, DH, Bussel, JB (2003) 21. Immunohematologic disorders. J Allergy Clin Immunol 111, S669–76

    PubMed  CAS  Google Scholar 

  • Venkatesh, J, Diamond, B (2004) Unpublished observations

    Google Scholar 

  • Vojdani, A, Campbell, AW, Anyanwu, E, Kashanian, A, Bock, K, Vojdani, E (2002) 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 129, 168–77

    Article  PubMed  CAS  Google Scholar 

  • Waterhouse, DM, Natale, RB, Cody, RL (1991) Breast cancer and paraneoplastic cerebellar degeneration. Cancer 68, 1835–41

    PubMed  CAS  Google Scholar 

  • Xaio, H, Banks, WA, Niehoff, ML, Morley, JE (2001) Effect of LPS on the permeability of the blood-brain barrier to insulin. Brain Res 896, 36–42

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Integrated Department of Immunology, National Jewish Medical Research Center, University of Colorado Health Sciences Center, 1400 Jackson St, K806, Denver, CO, 80206, USA

    J. S. Rice

  2. Department of Medicine, Columbia University Medical Center, 1130 St. Nicholas Avenue, Audobon III Bldg. 9th Fl. Rm 916, New York, NY, 10032, USA

    C. Kowal

  3. Department of Neurology and Neuroscience, The Burke Medical Research Institute, Weill Medical College of Cornell University, 785 Mamaroneck Avenue, White Plains, New York, NY, 10605, USA

    B. T. Volpe & L. A. DeGiorgio

  4. Department of Medicine, Division of Rheumatology, Columbia University Medical Center, 630 West 168th Street PH8E Suite 101, New York, NY, 10032, USA

    B. Diamond

Authors
  1. J. S. Rice
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Kowal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. T. Volpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. A. DeGiorgio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Diamond
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA

    Michael B.A. Oldstone M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Rice, J.S., Kowal, C., Volpe, B.T., DeGiorgio, L.A., Diamond, B. (2005). Molecular Mimicry: Anti-DNA Antibodies Bind Microbial and Nonnucleic Acid Self-Antigens. In: Oldstone, M.B. (eds) Molecular Mimicry: Infection-Inducing Autoimmune Disease. Current Topics in Microbiology and Immunology, vol 296. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-30791-5_8

Download citation

Publish with us

Policies and ethics

Search

Navigation