autoimmune diseases of the nervous system

Summary

Summary: Disorders caused by cellular or humoral immune responses primarily directed towards nervous system autoantigens. The immune response may be directed towards specific tissue components (e.g., myelin) and may be limited to the central nervous system (e.g., MULTIPLE SCLEROSIS) or the peripheral nervous system (e.g., GUILLAIN-BARRE SYNDROME).

Top Publications

  1. Berger A, Sommer A, Zwarg J, Hamdorf M, Welzel K, Esly N, et al. SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. PLoS Pathog. 2011;7:e1002425 pubmed publisher
    ..Taken together, we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection confirming SAMHD1 as a potent lentiviral restriction factor...
  2. Benkler M, Agmon Levin N, Shoenfeld Y. Parkinson's disease, autoimmunity, and olfaction. Int J Neurosci. 2009;119:2133-43 pubmed publisher
    ..We hope that understanding the nature of this disease may lay the ground for successes in the quest to halt the progressive neurodegenerative process...
  3. Ramantani G, Kohlhase J, Hertzberg C, Innes A, Engel K, Hunger S, et al. Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutières syndrome. Arthritis Rheum. 2010;62:1469-77 pubmed publisher
    ..In this study we further characterized the phenotypic spectrum of this disease...
  4. Rice G, Forte G, Szynkiewicz M, Chase D, Aeby A, Abdel Hamid M, et al. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013;12:1159-69 pubmed publisher
    ..The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials...
  5. Crow Y. Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci. 2011;1238:91-8 pubmed publisher
  6. Ablasser A, Hemmerling I, Schmid Burgk J, Behrendt R, Roers A, Hornung V. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. J Immunol. 2014;192:5993-7 pubmed publisher
    ..These findings indicate a key role of cyclic GMP-AMP synthase for the initiation of self-DNA-induced autoimmune disorders, thus providing important implications for novel therapeutic approaches. ..
  7. Dalmau J, Gleichman A, Hughes E, Rossi J, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7:1091-8 pubmed publisher
    ..We aimed to analyse the clinical and immunological features of patients with the disorder and examine the effects of antibodies against NMDA receptors in neuronal cultures...
  8. Manel N, Littman D. Hiding in plain sight: how HIV evades innate immune responses. Cell. 2011;147:271-4 pubmed publisher
    ..Here we discuss implications of this discovery for induction of antiviral protective immunity...
  9. Crow Y, Vanderver A, Orcesi S, Kuijpers T, Rice G. Therapies in Aicardi-Goutières syndrome. Clin Exp Immunol. 2014;175:1-8 pubmed publisher
    ..We then discuss the pathogenesis of AGS from a molecular and cell biology perspective. Finally, we suggest possible treatment strategies in light of these emerging insights...

More Information

Publications62

  1. Figiel M, Chon H, Cerritelli S, Cybulska M, Crouch R, Nowotny M. The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutières syndrome defects. J Biol Chem. 2011;286:10540-50 pubmed publisher
    ..Our model indicates that the difference in substrate preference stems from the different position of the crucial tyrosine residue involved in substrate binding and recognition. ..
  2. Rychlik M, Chon H, Cerritelli S, Klimek P, Crouch R, Nowotny M. Crystal structures of RNase H2 in complex with nucleic acid reveal the mechanism of RNA-DNA junction recognition and cleavage. Mol Cell. 2010;40:658-70 pubmed publisher
    ..Junction recognition is important for the removal of RNA embedded in DNA and may play an important role in DNA replication and repair. ..
  3. Rice G, del Toro Duany Y, Jenkinson E, Forte G, Anderson B, Ariaudo G, et al. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet. 2014;46:503-509 pubmed publisher
    ..Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation. ..
  4. Rehwinkel J, Maelfait J, Bridgeman A, Rigby R, Hayward B, Liberatore R, et al. SAMHD1-dependent retroviral control and escape in mice. EMBO J. 2013;32:2454-62 pubmed publisher
    ..This shows that SAMHD1 can restrict lentiviruses in vivo and that nucleotide starvation is an evolutionarily conserved antiviral mechanism. ..
  5. Wilhelm K, Yanamandra K, Gruden M, Zamotin V, Malisauskas M, Casaite V, et al. Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients. Eur J Neurol. 2007;14:327-34 pubmed
    ..Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD...
  6. Beck Engeser G, Eilat D, Wabl M. An autoimmune disease prevented by anti-retroviral drugs. Retrovirology. 2011;8:91 pubmed publisher
    ..However, inhibition of reverse transcription by the inhibitor zidovudine (AZT) did not ameliorate the disease, weakening the link to retroelements...
  7. Reijns M, Bubeck D, Gibson L, Graham S, Baillie G, Jones E, et al. The structure of the human RNase H2 complex defines key interaction interfaces relevant to enzyme function and human disease. J Biol Chem. 2011;286:10530-9 pubmed publisher
    ..Altogether, we locate 25 out of 29 residues mutated in AGS patients, establishing a firm basis for future investigations into disease pathogenesis and function of the RNase H2 enzyme...
  8. Rabe B. Aicardi-Goutières syndrome: clues from the RNase H2 knock-out mouse. J Mol Med (Berl). 2013;91:1235-40 pubmed publisher
    ..However, recent evidence gathered from RNase H2 knock-out mice might provide additional insight into the molecular mechanisms underlying AGS development and a potential role of DNA damage as a trigger of autoimmunity is discussed. ..
  9. Thiele H, du Moulin M, Barczyk K, George C, Schwindt W, Nurnberg G, et al. Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. Hum Mutat. 2010;31:E1836-50 pubmed publisher
    ..The observed vascular changes most likely reflect a vasculitis caused by dysregulated inflammatory stress response...
  10. Baldauf H, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, et al. SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells. Nat Med. 2012;18:1682-7 pubmed publisher
    ..Together, these findings may unveil new ways to interfere with the immune evasion and T cell immunopathology of pandemic HIV-1...
  11. Vincent A, Lang B, Kleopa K. Autoimmune channelopathies and related neurological disorders. Neuron. 2006;52:123-38 pubmed
  12. Gall A, Treuting P, Elkon K, Loo Y, Gale M, Barber G, et al. Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity. 2012;36:120-31 pubmed publisher
    ..These findings reveal a stepwise progression of autoimmune disease in Trex1-deficient mice, with implications for the treatment of AGS and related disorders...
  13. Rice G, Kasher P, Forte G, Mannion N, Greenwood S, Szynkiewicz M, et al. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat Genet. 2012;44:1243-8 pubmed publisher
    ..Considering recent insights derived from the study of other AGS-related proteins, we speculate that ADAR1 may limit the cytoplasmic accumulation of the dsRNA generated from genomic repetitive elements...
  14. Powell R, Holland P, Hollis T, Perrino F. Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase. J Biol Chem. 2011;286:43596-600 pubmed publisher
    ..We show that SAMHD1 contains a dGTP-regulated deoxynucleotide triphosphohydrolase. We propose that Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication...
  15. Church A, Dale R, Lees A, Giovannoni G, Robertson M. Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry. 2003;74:602-7 pubmed
    ..Anti-basal ganglia antibodies (ABGA) are present in most cases of acute Sydenham's chorea, but rarely in controls...
  16. Cua D, Sherlock J, Chen Y, Murphy C, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744-8 pubmed
    ..In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages...
  17. Thieben M, Lennon V, Boeve B, Aksamit A, Keegan M, Vernino S. Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody. Neurology. 2004;62:1177-82 pubmed
  18. Amor Dorado J, Barreira Fernández M, Regueiro Villarin S, Gonzalez Gay M. [Audiovestibular manifestations in systemic vasculitis]. Acta Otorrinolaringol Esp. 2009;60:432-42 pubmed publisher
    ..Improvement of audiovestibular function is frequently observed in patients with giant cell arteritis following corticosteroid therapy...
  19. Brodtkorb E. [Autoimmune epilepsy]. Tidsskr Nor Laegeforen. 2006;126:782 pubmed
  20. Tumani H, Brettschneider J. Biochemical markers of autoimmune diseases of the nervous system. Curr Pharm Des. 2012;18:4556-63 pubmed
    ..We provide an overview over the widening field of autoimmune diseases of the central and peripheral nervous system and discuss the current state of biomarker research and its relevance for clinical practice. ..
  21. Okada H, Khoury S. Type17 T-cells in central nervous system autoimmunity and tumors. J Clin Immunol. 2012;32:802-8 pubmed publisher
    ..The insight gained from these findings may lead to the development of novel therapeutic and prophylactic strategies for CNS autoimmunity and tumors...
  22. Banwell B. The long (-itudinally extensive) and the short of it: transverse myelitis in children. Neurology. 2007;68:1447-9 pubmed
  23. Tsunoda I, Libbey J, Fujinami R. Sequential polymicrobial infections lead to CNS inflammatory disease: possible involvement of bystander activation in heterologous immunity. J Neuroimmunol. 2007;188:22-33 pubmed
    ..While MCMV alone caused no CNS disease, control VV-infected mice followed with MCMV developed mild CNS inflammation. Thus, heterologous virus infections can induce CNS pathology...
  24. Mehta S, Morgan J, Sethi K. Paraneoplastic movement disorders. Curr Neurol Neurosci Rep. 2009;9:285-91 pubmed
    ..Although variable, treatment and prognosis of NPSs rely heavily on treatment of the underlying malignancy and immunotherapy...
  25. Gajanayake I, Niessen S, Cherubini G, Shelton G. Autoimmune myasthenia gravis and dysautonomia in a dog. J Small Anim Pract. 2008;49:593-5 pubmed publisher
    ..This is the first report of coexisting autoimmune myasthenia gravis and dysautonomia in a non-human species. The concomitant diseases may suggest a common immunopathological aetiology...
  26. Rupp A, Cunningham M, Yao D, Furukawa K, Willison H. The effects of age and ganglioside composition on the rate of motor nerve terminal regeneration following antibody-mediated injury in mice. Synapse. 2013;67:382-9 pubmed publisher
    ..In summary, the rate of mNT regeneration following anti-ganglioside antibody and complement-mediated injury does not differ majorly between young adult and aged mice irrespective of the expression of particular gangliosides...
  27. Hofer M, Campbell I. Type I interferon in neurological disease-the devil from within. Cytokine Growth Factor Rev. 2013;24:257-67 pubmed publisher
    ..Thus, targeting IFN-I may be an effective strategy for the treatment of AGS as well as some other autoimmune and infectious neurological "interferonopathies". ..
  28. Elovaara I, Apostolski S, van Doorn P, Gilhus N, Hietaharju A, Honkaniemi J, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol. 2008;15:893-908 pubmed publisher
  29. Goncalves A, Karayel E, Rice G, Bennett K, Crow Y, Superti Furga G, et al. SAMHD1 is a nucleic-acid binding protein that is mislocalized due to aicardi-goutières syndrome-associated mutations. Hum Mutat. 2012;33:1116-22 pubmed publisher
    ..Overall, these data suggest that SAMHD1 has a role in the nucleus that, if disrupted by mutation, leads to cytosolic accumulation of SAMHD1 and autoimmune disease...
  30. Magy L. [Dysimmune peripheral neuropathies]. Rev Neurol (Paris). 2006;162:495-501 pubmed
    ..New scales will probably arise in the next few years, to be used in neuropathies from other causes. These scales will have to be strictly validated to be used in the daily medical practice...
  31. Baker S, Morillo C, Vernino S. Autoimmune autonomic ganglionopathy with late-onset encephalopathy. Auton Neurosci. 2009;146:29-32 pubmed publisher
    ..It is tempting to speculate that CNS alpha4 or alpha7 antibodies may have precipitated the treatment-responsive encephalopathy...
  32. Bhat R, Steinman L. Innate and adaptive autoimmunity directed to the central nervous system. Neuron. 2009;64:123-32 pubmed publisher
  33. Florance Ryan N, Dalmau J. Update on anti-N-methyl-D-aspartate receptor encephalitis in children and adolescents. Curr Opin Pediatr. 2010;22:739-44 pubmed publisher
    ..We review here the main clinical features and differential diagnosis and provide algorithms of the clinical correlates of antibody-mediated decrease of NMDAR and a suggested treatment approach...
  34. Cole A. Hippocampal sclerosis: an inflammatory hypothesis. Neurology. 2007;69:1204-5 pubmed
  35. Giani T, Simonini G, Lunardi C, Puccetti A, De Martino M, Falcini F. Juvenile psoriatic arthritis and acquired sensorineural hearing loss in a teenager: is there an association?. Clin Exp Rheumatol. 2006;24:344-6 pubmed
    ..The young age of our patient seems to suggest a genetic susceptibility to autoimmunity and supports the concept of associated autoimmune diseases...
  36. Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol. 2010;9:67-76 pubmed publisher
    ..Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved...
  37. Garg A. Vascular brain pathologies. Neuroimaging Clin N Am. 2011;21:897-926, ix pubmed publisher
    ..This article focuses on acquired vascular pathologies of brain prevalent in tropical countries that are encountered in clinical practice...
  38. Nakamura T. [Infectious agents as the triggers for the pathogenesis of the neuroimmunological disorders]. Nihon Rinsho. 2008;66:1056-64 pubmed
    ..We, herein, discuss about the relationship between infectious agents and these diseases...
  39. Espay A, Chen R. Rigidity and spasms from autoimmune encephalomyelopathies: stiff-person syndrome. Muscle Nerve. 2006;34:677-90 pubmed
  40. Deakin J, Lennox B, Zandi M. Antibodies to the N-methyl-D-aspartate receptor and other synaptic proteins in psychosis. Biol Psychiatry. 2014;75:284-91 pubmed publisher
    ..We discuss the evidence for this from the field of paraneoplastic neurologic syndromes and the discovery of novel cell surface antigen central nervous system autoimmune syndromes. ..
  41. Koski C, Patterson J. Intravenous immunoglobulin use for neurologic diseases. J Infus Nurs. 2006;29:S21-8 pubmed
    ..This article gives an overview of some autoimmune neurologic diseases and explores the clinical evidence supporting the use of IVIG...
  42. Köller H, Schroeter M, Feischen H, Hartung H, Kieseier B. Subcutaneous self-infusions of immunoglobulins as a potential therapeutic regimen in immune-mediated neuropathies. J Neurol. 2006;253:1505-6 pubmed
  43. Seshadri M, Stein S, Chowdhury U. The spectrum of tic disorders (2). Community Pract. 2007;80:40, 42 pubmed
  44. Chahwan C, Chahwan R. Aicardi-Goutieres syndrome: from patients to genes and beyond. Clin Genet. 2012;81:413-20 pubmed publisher
  45. Vallat J. [Axonal involvement in dysimmune neuropathies]. Rev Neurol (Paris). 2007;163 Spec No 1:3S5-11 pubmed
  46. Antozzi C. Immunoadsorption in patients with autoimmune ion channel disorders of the peripheral nervous system. Atheroscler Suppl. 2013;14:219-22 pubmed publisher
  47. Cañas C, Rincón Hoyos H, Izquierdo J, Bonilla Abadía F, Arbeláez Cortés A. Psychiatric manifestations in patients with dysautonomy associated with systemic lupus erythematosus. Lupus. 2012;21:1128-30 pubmed publisher
    ..A provocative test with SPECT with 99mTc-HmPAO to be done during the episode of orthostatic hypotension may contribute to clinical assessment of complex changes in cerebral regional perfusion...
  48. Serratrice G, Pellissier J, Serratrice J, De Paula A. [Limbic encephalitis--evolving concepts]. Bull Acad Natl Med. 2008;192:1531-41; discussion 1541-2 pubmed
    ..Limbic encephalitis can also reveal Hodgkin's disease, as in a case observed by the authors...
  49. Suzumura A. [Microglia in pathophysiology of neuroimmunological disorders]. Nihon Rinsho. 2013;71:801-6 pubmed
    ..These factors affect neuronal, glial and endothelial cell functions. Thus, they are believed to play a predominant role in the development of neuroimmunological disorders as APC and effector cells...
  50. Koning L. [Encephalitis lethargica in the Netherlands; renewed interest in a mysterious disease]. Ned Tijdschr Geneeskd. 2009;153:B326 pubmed
    ..Recent research suggests that an autoimmune response targeted at the basal ganglia, possibly caused by a streptococcal infection, plays a role in the aetiology of the disease...
  51. Ibrahim H, Dimachkie M, Shaibani A. A review: the use of rituximab in neuromuscular diseases. J Clin Neuromuscul Dis. 2010;12:91-102 pubmed publisher
    ..In this article, we review and discuss the available literature on rituximab in treatment of various autoimmune neuromuscular diseases...
  52. Kuki I, Kawawaki H, Okazaki S, Hattori Y, Horino A, Higuchi O, et al. Autoimmune autonomic ganglionopathy in a pediatric patient presenting with acute encephalitis. Brain Dev. 2016;38:605-8 pubmed publisher
    ..This observation indicates that AAG should be suspected in patients manifesting acute encephalitis characterized by preceding and prolonged autonomic symptoms, and immunomodulating therapy from an early stage can be effective. ..
  53. Achleitner M, Kleefisch M, Hennig A, Peschke K, Polikarpova A, Oertel R, et al. Lack of Trex1 Causes Systemic Autoimmunity despite the Presence of Antiretroviral Drugs. J Immunol. 2017;199:2261-2269 pubmed publisher
    ..Our data do not support the concept of retroelement-derived cDNA as key triggers of systemic autoimmunity in Trex1-deficient humans and mice and motivate the continuing search for the pathogenic IFN-inducing Trex1 substrate. ..