Spinal cord injury triggers systemic autoimmunity: Evidence for chronic B lymphocyte activation and lupus-like autoantibody synthesis

Journal of Neurochemistry

Volumn 99, Issue 4, 2006, Pages 1073-1087

  Ankeny, Daniel P ^a   Lucin, Kurt M ^a   Sanders, Virginia M ^a   McGaughy, Violeta M ^a   Popovich, Phillip G ^a,b  

^a THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

^b 2078 Graves Hall ^*  (United States)

Author keywords

Antibodies; Autoimmunity; B cells; CNS injury; Neuroinflammation

Indexed keywords

ANTIBODY; AUTOANTIBODY; BRAIN PROTEIN; DNA; RNA;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; CELL ACTIVATION; CELL DIFFERENTIATION; CELL FUNCTION; CELL PROLIFERATION; CONTROLLED STUDY; EXCITOTOXICITY; FEMALE; HISTOPATHOLOGY; LAMINECTOMY; MOUSE; NONHUMAN; PRIORITY JOURNAL; SPINAL CORD INJURY;

ANIMALS; AUTOANTIBODIES; AUTOIMMUNE DISEASES OF THE NERVOUS SYSTEM; B-LYMPHOCYTES; CELLS, CULTURED; CENTRAL NERVOUS SYSTEM; CHEMOTAXIS, LEUKOCYTE; CROSS REACTIONS; DISEASE MODELS, ANIMAL; DNA-BINDING PROTEINS; FEMALE; LUPUS ERYTHEMATOSUS, SYSTEMIC; LYMPHOCYTE ACTIVATION; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NERVE TISSUE PROTEINS; NEUROIMMUNOMODULATION; NUCLEIC ACIDS; OLIGOCLONAL BANDS; SPINAL CORD INJURIES;

MAMMALIA;

EID: 33750452715     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2006.04147.x     Document Type: Article

References (74)

1. Abdul-Majid K. B., Stefferl A., Bourquin C., Lassmann H., Linington C., Olsson T., Kleinau S. and Harris R. A. (2002) Fc receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis. Scand. J. Immunol. 55, 70-81.
2. Anderson A. J., Robert S., Huang W., Young W. and Cotman C. W. (2004) Activation of complement pathways after contusion-induced spinal cord injury. J. Neurotrauma 21, 1831-1846.
3. Barrat F. J., Meeker T., Gregorio J., Chan J. H., Uematsu S., Akira S., Chang B., Duramad O. and Coffman R. L. (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med. 202, 1131-1139.
4. Beuche W. and Friede R. L. (1986) Myelin phagocytosis in Wallerian degeneration of peripheral nerves depends on silica-sensitive, bg/bg-negative and Fc-positive monocytes. Brain Res. 378, 97-106.
5. Broadwell R. D. and Sofroniew M. V. (1993) Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Exp. Neurol. 120, 245-263.
6. Bruck W. and Friede R. L. (1991) The role of complement in myelin phagocytosis during PNS wallerian degeneration. J. Neurol. Sci. 103, 182-187.
7. Casciola-Rosen L. A., Anhalt G. and Rosen A. (1994) Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J. Exp. Med. 179, 1317-1330.
8. Charles P. C., Weber K. S., Cipriani B. and Brosnan C. F. (1999) Cytokine, chemokine and chemokine receptor mRNA expression in different strains of normal mice: implications for establishment of a Th1/Th2 bias. J. Neuroimmunol. 100, 64-73.
9. Chouchakova N., Skokowa J., Baumann U., Tschernig T., Philippens K. M., Nieswandt B., Schmidt R. E. and Gessner J. E. (2001) Fcc RIII-mediated production of TNF-α induces immune complex alveolitis independently of CXC chemokine generation. J. Immunol. 166, 5193-5200.
10. Christensen S. R., Kashgarian M., Alexopoulou L., Flavell R. A., Akira S. and Shlomchik M. J. (2005) Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J. Exp. Med. 202, 321-331.
11. Cohen P. L., Caricchio R., Abraham V., Camenisch T. D., Jennette J. C., Roubey R. A., Earp H. S., Matsushima G. and Reap E. A. (2002) Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J. Exp. Med. 196, 135-140.
12. Corcione A., Casazza S., Ferretti E., Giunti D., Zappia E., Pistorio A., Gambini C., Mancardi G. L., Uccelli A. and Pistoia V. (2004) Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc. Natl Acad. Sci. USA 101, 11 064-11 069.
13. Davidoff G. N., Roth E. J. and Richards J. S. (1992) Cognitive deficits in spinal cord injury: epidemiology and outcome. Arch. Phys. Med. Rehabil. 73, 275-284.
14. DeGiorgio L. A., Konstantinov K. N., Lee S. C., Hardin J. A., Volpe B. T. and Diamond B. (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat. Med. 7, 1189-1193.
15. Dowler R. N., Harrington D. L., Haaland K. Y., Swanda R. M., Fee F. and Fiedler K. (1997) Profiles of cognitive functioning in chronic spinal cord injury and the role of moderating variables. J. Int. Neuropsychol. Soc. 3, 464-472.
16. Dyer J. K., Bourque J. A. and Steeves J. D. (1998) Regeneration of brainstem-spinal axons after lesion and immunological disruption of myelin in adult rat. Exp. Neurol. 154, 12-22.
17. Freddo L., Hays A. P., Nickerson K. G. et al. (1986) Monoclonal anti-DNA IgMκ in neuropathy binds to myelin and to a conformational epitope formed by phosphatidic acid and gangliosides. J. Immunol. 137, 3821-3825.
18. Friou G. J., Finch S. C. and Detre K. D. (1958) Interaction of nuclei and globulin from lupus erythematosis serum demonstrated with fluorescent antibody. J. Immunol. 80, 324-329.
19. Genain C. P., Cannella B., Hauser S. L. and Raine C. S. (1999) Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat. Med. 5, 170-175.
20. Griot-Wenk M., Griot C., Pfister H. and Vandevelde M. (1991) Antibody-dependent cellular cytotoxicity in anti-myelin antibody-induced oligodendrocyte damage in vitro. J. Neuroimmunol. 33, 145-155.
21. Hanayama R., Tanaka M., Miyasaka K., Aozasa K., Koike M., Uchiyama Y. and Nagata S. (2004) Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304, 1147-1150.
22. Hauben E., Butovsky O., Nevo U. et al. (2000) Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J. Neurosci. 20, 6421-6430.
23. Hayes K. C., Hull T. C., Delaney G. A., Potter P. J., Sequeira K. A., Campbell K. and Popovich P. G. (2002) Elevated serum titers of proinflammatory cytokines and CNS autoantibodies in patients with chronic spinal cord injury. J. Neurotrauma 19, 753-761.
24. Huang D. W., McKerracher L., Braun P. E. and David S. (1999) A therapeutic vaccine approach to stimulate axon regeneration in the adult mammalian spinal cord. Neuron 24, 639-647.
25. Huerta P. T., Kowal C., DeGiorgio L. A., Volpe B. T. and Diamond B. (2006) Immunity and behavior: antibodies alter emotion. Proc. Natl Acad. Sci. USA 103, 678-683.
26. Ibarra A., Martinez S., Reyes J., Meza-Lucas A., Mandujano A., Grijalva I., Madrazo I. and Correa D. (2000) Search for an IgG response against neural antigens in experimental spinal cord injury. Neuroscience 96, 3-5.
27. Jakeman L. B., Guan Z., Wei P., Ponnappan R., Dzwonczyk R., Popovich P. G. and Stokes B. T. (2000) Traumatic spinal cord injury produced by controlled contusion in mouse. J. Neurotrauma 17, 299-319.
28. Jones T. B., Basso D. M., Sodhi A., Pan J. Z., Hart R. P., MacCallum R. C., Lee S., Whitacre C. C. and Popovich P. G. (2002) Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J. Neurosci. 22, 2690-2700.
29. Jones T. B., Ankeny D. P., Guan Z., McGaughy V., Fisher L. C., Basso D. M. and Popovich P. G. (2004) Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats. J. Neurosci. 24, 3752-3761.
30. Kigerl K. A., McGaughy V. M. and Popovich P. G. (2006) Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. J. Comp. Neurol. 494, 578-594.
31. Kil K., Zang Y. C. Q., Yang D., Markowski J., Fuoco G. S., Vendetti G. C., Rivera V. M. and Zhang J. Z. (1999) T-cell responses to myelin basic protein in patients with spinal cord injury and multiple sclerosis. J. Neuroimmunol. 98, 201-207.
32. Kotter M. R., Li W. W., Zhao C. and Franklin R. J. (2006) Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J. Neurosci. 26, 328-332.
33. Kowal C., DeGiorgio L. A., Nakaoka T., Hetherington H., Huerta P. T., Diamond B. and Volpe B. T. (2004) Cognition and immunity; antibody impairs memory. Immunity 21, 179-188.
34. Kozlowski G. P., Sterzl I. and Nilaver G. (1992) Localization patterns for immunoglobulins and albumins in the brain suggest diverse mechanisms for their transport across the blood-brain barrier (BBB). Prog. Brain Res. 91, 149-154.
35. Lau C. M., Broughton C., Tabor A. S. et al. (2005) RNA-associated autoantigens activate B cells by combined B cell antigen receptor/ Toll-like receptor 7 engagement. J. Exp. Med. 202, 1171-1177.
36. Lu J., Moochhala S., Kaur C. and Ling E. A. (2001) Cellular inflammatory response associated with breakdown of the blood-brain barrier after closed head injury in rats. J. Neurotrauma 18, 399-408.
37. Lyons J. A., San M., Happ M. P. and Cross A. H. (1999) B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide. Eur. J. Immunol. 29, 3432-3439.
38. Maron R., Hancock W. W., Slavin A., Hattori M., Kuchroo V. and Weiner H. L. (1999) Genetic susceptibility or resistance to autoimmune encephalomyelitis in MHC congenic mice is associated with differential production of pro- and anti-inflammatory cytokines. Int. Immunol. 11, 1573-1580.
39. Means T. K., Latz E., Hayashi F., Murali M. R., Golenbock D. T. and Luster A. D. (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Invest. 115, 407-417.
40. Merkler D., Oertle T., Buss A., Pinschewer D. D., Schnell L., Bareyre F. M., Kerschensteiner M., Buddeberg B. S. and Schwab M. E. (2003) Rapid induction of autoantibodies against Nogo-A and MOG in the absence of an encephalitogenic T cell response: implication for immunotherapeutic approaches in neurological diseases. FASEB J. 17, 2275-2277.
41. Mevorach D., Zhou J. L., Song X. and Elkon K. B. (1998) Systemic exposure to irradiated apoptotic cells induces autoantibody production. J. Exp. Med. 188, 387-392.
42. Mizrachi Y., Ohry A., Aviel A., Rozin R., Brooks M. E. and Schwartz M. (1983) Systemic humoral factors participating in the course of spinal cord injury. Paraplegia 21, 287-293.
43. Moalem G., Leibowitz-Amit R., Yoles E., Mor F., Cohen I. R. and Schwartz M. (1999) Autoimmune T-cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 5, 49-55.
44. Mosley K. and Cuzner M. L. (1996) Receptor-mediated phagocytosis of myelin by macrophages and microglia: effect of opsonization and receptor blocking agents. Neurochem. Res. 21, 481-487.
45. Orr C. F., Rowe D. B., Mizuno Y., Mori H. and Halliday G. M. (2005) A possible role for humoral immunity in the pathogenesis of Parkinson's disease. Brain 128, 2665-2674.
46. Poduslo J. F. and Curran G. L. (1996) Polyamine modification increases the permeability of proteins at the blood-nerve and blood-brain barriers. J. Neurochem. 66, 1599-1609.
47. Popovich P. G., Horner P. J., Mullin B. B. and Stokes B. T. (1996a) A quantitative spatial analysis of the blood-spinal cord barrier I. Permeability changes after experimental spinal contusion injury. Exp. Neurol. 142, 258-275.
48. Popovich P. G., Stokes B. T. and Whitacre C. C. (1996b) Concept of autoimmunity following spinal cord injury: Possible roles for T lymphocytes in the traumatized central nervous system. J. Neurosci. Res. 45, 349-363.
49. Popovich P. G., Wei P. and Stokes B. T. (1997) The cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J. Comp. Neurol. 377, 443-464.
50. Popovich P. G., Stuckman S., Gienapp I. E. and Whitacre C. C. (2001) Alterations in immune cell phenotype and function after experimental spinal cord injury. J. Neurotrauma 18, 957-966.
51. Prineas J. W. (1979) Multiple sclerosis: presence of lymphatic capillaries and lymphoid tissue in the brain and spinal cord. Science 203, 1123-1125.
52. Raine C. S., Cannella B., Hauser S. L. and Genain C. P. (1999) Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions: a case for antigen-specific antibody mediation. Ann. Neurol. 46, 144-160.
53. Ray S. K., Putterman C. and Diamond B. (1996) Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease. Proc. Natl Acad. Sci. USA 93, 2019-2024.
54. Rodriguez M. and Lennon V. A. (1990) Immunoglobulins promote remyelination in the central nervous system. Ann. Neurol. 27, 12-17.
55. Rose M. L., Birbeck M. S., Wallis V. J., Forrester J. A. and Davies A. J. (1980) Peanut lectin binding properties of germinal centres of mouse lymphoid tissue. Nature 284, 364-366.
56. Rudehill S., Muhallab S., Wennersten A., von Gertten C., Al Nimer F., Sandberg-Nordqvist A. C., Holmin S. and Mathiesen T. (2006) Autoreactive antibodies against neurons and basal lamina found in serum following experimental brain contusion in rats. Acta Neurochir. (Wien) 148, 199-205.
57. Schnell L. and Schwab M. E. (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343, 269-272.
58. Schuller E., Delasnerie N. and Lebon P. (1978) DNA and RNA antibodies in serum and CSF of multiple sclerosis and subacute sclerosing panencephalitis patients. J. Neurol. Sci. 37, 31-36.
59. Schwab C. and McGeer P. L. (2002) Complement activated C4d immunoreactive oligodendrocytes delineate small cortical plaques in multiple sclerosis. Exp. Neurol. 174, 81-88.
60. Serafini B., Rosicarelli B., Magliozzi R., Stigliano E. and Aloisi F. (2004) Detection of ectopic B cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol. 14, 164-174.
61. Sroga J. M., Jones T. B., Kigerl K. A., McGaughy V. M. and Popovich P. G. (2003) Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J. Comp. Neurol. 462, 223-240.
62. Stein T. D., Fedynyshyn J. P. and Kalil R. E. (2002) Circulating autoantibodies recognize and bind dying neurons following injury to the brain. J. Neuropathol. Exp. Neurol. 61, 1100-1108.
63. Tan E. M. (1989) Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv. Immunol. 44, 93-151.
64. Tojo T. and Friou G. J. (1968) Lupus nephritis: varying complement-fixing properties of immunoglobulin G antibodies to antigens of cell nuclei. Science 161, 904-906.
65. Upender M. B. and Naegele J. R. (1999) Activation of microglia during developmentally regulated cell death in the cerebral cortex. Dev. Neurosci. 21, 491-505.
66. Vollmer J., Tluk S., Schmitz C. et al. (2005) Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8. J. Exp. Med. 202, 1575-1585.
67. Vrethem M., Henriksson A., Malm C., Olsson T. and Ernerudh J. (1992) Ig-secreting cells pass the blood-brain barrier: studies on j and k light chain secreting cells in plasma cell dyscrasia. J. Neuroimmunol. 41, 189-194.
68. de Vries H. E., Blom-Roosemalen M. C. M., van Oosten M., de Boer A. G., van Berkel T. J. C., Breimer D. D. and Kuiper J. (1996) The influence of cytokines on the integrity of the blood-brain barrier in vitro. J. Neuroimmunol. 64, 37-43.
69. Warren W. D. and Berton M. T. (1995) Induction of germ-line c1 and epsilon Ig gene expression in murine B cells. IL-4 and the CD40 ligand-CD40 interaction provide distinct but synergistic signals. J. Immunol. 155, 5637-5646.
70. Willenborg D. O. and Prowse S. J. (1983) Immunoglobulin-deficient rats fail to develop experimental allergic encephalomyelitis. J. Neuroimmunol. 5, 99-109.
71. Williamson R. A., Burgoon M. P., Owens G. P. et al. (2001) Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis. Proc. Natl Acad. Sci. USA 98, 1793-1798.
72. Yasojima K., Schwab C., McGeer E. G. and McGeer P. L. (1999) Up-regulated production and activation of the complement system in Alzheimer's disease brain. Am. J. Pathol. 154, 927-936.
73. Yoles E., Hauben E., Palgi O., Agranov E., Gothilf A., Cohen A., Kuchroo V., Cohen I. R., Weiner H. and Schwartz M. (2001) Protective autoimmunity is a physiological response to CNS trauma. J. Neurosci. 21, 3740-3748.
74. Zhang Z., Trautmann K. and Schluesener H. J. (2005) Microglia activation in rat spinal cord by systemic injection of TLR3 and TLR7/8 agonists. J. Neuroimmunol. 164, 154-160.