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DOI: 10.1590/0004-282X20170081
Polyspecific antibodies without persisting antigen in multiple sclerosis, neurolupus and Guillain-Barré syndrome: immune network connectivity in chronic diseases
Anticorpos poliespecíficos sem antígeno persistente em esclerose múltipla, neurolupus e síndrome de Guillain-Barré: conectividade imunológica em doenças crçnicasABSTRACT
The polyspecific antibody synthesis in multiple sclerosis (MS) gained diagnostic relevance with the frequent combination of measles-, rubella- and varicella zoster antibodies (MRZ-antibody reaction) but their pathophysiological role remains unknown. This review connects the data for intrathecal polyspecific antibody synthesis in MS and neurolupus with observations in the blood of patients with Guillain-Barré syndrome (GBS). Simultaneously increased antibody and autoantibody titers in GBS blood samples indicate that the polyspecific antibodies are based on a general property of an immune network, supported by the deterministic day-to-day concentration variation of antibodies in normal blood. Strongly correlated measles- and rubella- antibody variations point to a particular connectivity between the MRZ antibodies. The immune network, which provides serological memory in the absence of an antigen, implements the continuous change of the MRZ pattern in blood, not followed by the earlier immigrated B cells without corresponding connectivity in the brain. This may explain the different antibody patterns in cerebrospinal fluid, aqueous humor and blood of the individual MS patient. A complexity approach must implement a different view on causation in chronic diseases and causal therapies.
RESUMO
A síntese de anticorpos poliespecíficos em esclerose múltipla (EM) ganhou relevância diagnóstica com a combinação frequente de anticorpos contra sarampo, rubéola e varicela-zoster (reação de anticorpos MRZ), mas seu papel fisiopatológico permanece desconhecido. Esta revisão relaciona os dados da síntese intratecal de anticorpos poliespecíficos em EM e Neurolupus com observações no sangue de pacientes com síndrome de Guillain Barré (SGB). Simultaneamente, os títulos aumentados de anticorpos e autoanticorpos em amostras de sangue de SGB indicam que os anticorpos poliespecíficos se baseiam numa propriedade geral de uma rede imunitária, suportada pela variação determinística da concentração diária de anticorpos no sangue normal. As variações fortemente correlacionadas de anticorpos contra sarampo e rubéola apontam para uma conectividade particular entre os anticorpos MRZ. A rede imunitária, que fornece memória sorológica na ausência de um antígeno, implementa a mudança contínua do padrão MRZ no sangue, não seguida pelas células B que imigraram anteriormente sem conectividade no cérebro. Isto pode explicar os diferentes padrões de anticorpos no LCR, humor aquoso e sangue do paciente individual de EM. Uma abordagem complexa deve implementar uma visão diferente sobre a causalidade em doenças crçnicas e terapias causais.
Publikationsverlauf
Eingereicht: 11. April 2017
Angenommen: 20. April 2017
Artikel online veröffentlicht:
05. September 2023
© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Reiber H, Kruse-Sauter H, Quentin CD. Antibody patterns vary arbitrarily between cerebrospinal fluid and aqueous humor of the individual multiple sclerosis patient: specificity-independent pathological B cell function. J Neuroimmunol. 2015;278:247-54. https://doi.org/10.1016/j.jneuroim.2014.11.013
- 2 Vaughan K, Peters B, O’Connor KC, Martin R, Sette A. A molecular view of multiple sclerosis and experimental autoimmune encephalitis: what can we learn from the epitope data? J Neuroimmunol. 2014;267(1-2):73-85. https://doi.org/10.1016/j.jneuroim.2013.12.009
- 3 Nielsen PR, Kragstrup TW, Deleuran BW, Benros ME. Infections as risk factor for autoimmune diseases: a nationwide study. J Autoimmun. 2016;74:176-81. https://doi.org/10.1016/j.jaut.2016.05.013
- 4 Reiber H. Chronic diseases with delayed onset after vaccinations and infections: a complex systems approach to pathology and therapy. J Arch Milit Med. 2017; 5(2) e 12285, in press.
- 5 Hotopf M, David A, Hull L, Ismail K, Unwin C, Wessely S. Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study. BMJ. 2000;320(7246):1363-7. https://doi.org/10.1136/bmj.320.7246.1363
- 6 Shoenfeld Y, Aron-Maor A. Vaccination and autoimmunity: ‘vaccinosis’: a dangereous liaison? J Autoimmun. 2000;14(1):1-10. https://doi.org/10.1006/jaut.1999.0346
- 7 Graef IT, Henze T, Reiber H. Polyspezifische Immunreaktion im ZNS bei Autoimmun-Erkrankungen mit ZNS Beteiligung. Z Ärztl Fortbild. 1994;88:587-91.
- 8 Terryberry J, Sutjita M, Shoenfeld Y, Gilburd B, Tanne D, Lorber M et al. Myelin- and microbe-specific antibodies in Guillain-Barré syndrome. J Clin Lab Anal. 1995;9(5):308-19. https://doi.org/10.1002/jcla.1860090506
- 9 Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler. 1998;4(3):111-7. https://doi.org/10.1177/135245859800400304
- 10 Reiber H. Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases: diagnostic patterns not to be missed in neurology and psychiatry. Arq Neuropsiquiatr. 2016;74(4):337-50. https://doi.org/10.1590/0004-282X20160044
- 11 Reiber H. Knowledge-base for interpretation of cerebrospinal fluid data patterns: essentials in neurology and psychiatry. Arq Neuropsiquiatr. 2016;74(6):501-12. https://doi.org/10.1590/0004-282x20160066
- 12 Varela FJ, Coutinho A. Second generation immune networks. Immunol Today. 1991;12(5):159-66. https://doi.org/10.1016/S0167-5699(05)80046-5
- 13 Jacobi C, Lange P, Reiber H. Quantitation of intrathecal antibodies in cerebrospinal fluid of subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis: discrimination between microorganism-driven and polyspecific immune response. J Neuroimmunol. 2007;187(1-2):139-46. https://doi.org/10.1016/j.jneuroim.2007.04.002
- 14 Quentin CD, Reiber H. Fuchs´ heterochromic cyclitis: rubella virus antibodies and genome in aqueous humor. Am J Ophthalmol. 2004;138(1):46-54. https://doi.org/10.1016/j.ajo.2004.02.055
- 15 Sindic CJ, Monteyne P, Laterre EC. The intrathecal synthesis of virus-specific oligoclonal IgG in MS. J Neuroimmunol. 1994;54(1-2):75-80. https://doi.org/10.1016/0165-5728(94)90233-X
- 16 Felgenhauer K, Schädlich H, Nekic M, Ackermann R. Cerebrospinal fluid virus antibodies: a diagnostic indicator for multiple sclerosis. J Neurol Sci. 1985;71(2-3):292-9. https://doi.org/10.1016/0022-510X(85)90067-X
- 17 Jarius S, Franciotta D, Bergamaschi R, Rauer S, Wandinger KP, Petereit HF et al. Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2008;79(10):1134-6. https://doi.org/10.1136/jnnp.2007.133330
- 18 Jarius S, Eichhorn P, Jacobi C, Wildemann B, Wick M, Voltz R. The intrathecal, polyspecific antiviral immune response: specific for MS or a general marker of CNS autoimmunity? J Neurol Sci. 2009;280(1-2):98-100. https://doi.org/10.1016/j.jns.2008.08.002
- 19 Hottenrott T, Dersch R, Berger B, Rauer S, Eckenweiler M, Huzly D et al. The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort. Fluids Barriers CNS. 2015;12(1):27. https://doi.org/10.1186/s12987-015-0024-8
- 20 Conrad AJ, Chiang EY, Andeen LE, Avolio C, Walker SM, Baumhefner RW et al. Quantitation of intrathecal measles virus IgG antibody synthesis rate: subacute sclerosing panencephalitis and multiple sclerosis. J Neuroimmunol. 1994;54(1-2):99-108. https://doi.org/10.1016/0165-5728(94)90236-4
- 21 Robinson-Agramonte M, Reiber H, Cabrera-Gomez JA, Galvizu R. Intrathecal polyspecific immune response to neurotropic viruses in multiple sclerosis: a comparative report from Cuban patients. Acta Neurol Scand. 2007;115(5):312-8. https://doi.org/10.1111/j.1600-0404.2006.00755.x
- 22 Hirzel K. Avidität antiviraler Antikörper in Liquor cerebrospinalis und Serum bei akuten und chronischen Entzündungen des Zentralnervensystems [Diplomarbeit]. Goettingen: Biologische Fakultät der Universität Goettingen; 1997.
- 23 Gharavi AE, Reiber H. Affinity and avidity of autoantibodies. In: Peter JB, Shoenfeld Y, editors. Autoantibodies. Amsterdam: Elsevier; 1996. p.13-23
- 24 Luxton RW, Thompson EJ. Affinity distributions of antigen-specific IgG in patients with multiple sclerosis and in patients with viral encephalitis. J Immunol Methods. 1990;131(2):277-82. https://doi.org/10.1016/0022-1759(90)90199-6
- 25 Reiber H, Teut M, Pohl D, Rostasy KM, Hanefeld F. Paediatric and adult multiple sclerosis: age-related differences and time course of the neuroimmunological response in cerebrospinal fluid. Mult Scler. 2009;15(12):1466-80. https://doi.org/10.1177/1352458509348418
- 26 Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001;184(2):101-22. https://doi.org/10.1016/S0022-510X(00)00501-3
- 27 Reiber H, Ressel CB, Spreer A. Diagnosis of neuroborreliosis: improved knowledge base for qualified antibody analysis and cerebrospinal fluid data pattern related interpretations. Neurol Psychiatry Brain Res. 2013;19(4):159-69. https://doi.org/10.1016/j.npbr.2013.10.004
- 28 Reiber H. Flow rate of cerebrospinal fluid (CSF): a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci. 1994;122(2):189-203. https://doi.org/10.1016/0022-510X(94)90298-4
- 29 Bechter K, Reiber H, Herzog S, Fuchs D, Tumani H, Maxeiner HG. Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood-CSF barrier dysfunction. J Psychiatric Res. 2010;44(5):321-30. https://doi.org/10.1016/j.jpsychires.2009.08.008
- 30 Stewart J, Varela FJ. Exploring the meaning of connectivity in the immune network. Immunol Rev. 1989;110(1):37-61. https://doi.org/10.1111/j.1600-065X.1989.tb00026.x
- 31 Heitmann S. Dynamik der polyspezifischen Immunreaktion bei nosokomialen Infektionen [Dissertation]. Goettingen: Med Fakultät der Georg August Universität Goettingen; 2002 .
- 32 Lundkvist I, Coutinho A, Varela F, Holmberg D. Evidence for a functional idiotypic network among natural antibodies in normal mice. Proc Natl Acad Sci. 1989;86(13):5074-8. https://doi.org/10.1073/pnas.86.13.5074
- 33 Pincus S. Approximate entropy (ApEn) as a complexity measure. Chaos. 1995;5(1):110-7. https://doi.org/10.1063/1.166092
- 34 Cysarz D, Bettermann H, Leeuwen P. Entropies of short binary sequences in heart period dynamics. Am J Physiol Heart Circ Physiol. 2000;278(6):H2163-72.
- 35 Mandelbrot BB. The fractal geometry of nature. New York: WH Freeman; 1982.
- 36 Reiber H. Die Komplexität biologischer Gestalt als zeitunabhängiges Konstrukt im Zustands-Raum. Zum naturwissenschaftlichen Umgang mit Qualitäten. In: Zeilinger D, editor. VorSchein, Jahrbuch der Ernst-Bloch- Assoziation, Nürnberg:Antogo; 2007. p. 39-61.
- 37 Rajewsk K. Clonal selection and learning in the antibody system. Nature. 1996;381(6585):751-8. https://doi.org/10.1038/381751a0
- 38 Perelson AS. Immune network theory. Immunol Rev. 1989;110(1):5-36. https://doi.org/10.1111/j.1600-065X.1989.tb00025.x
- 39 Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science. 2002;298(5601):2199-202. https://doi.org/10.1126/science.1076071
- 40 Coutinho A. The network theory:21 years later. Scand J Immunol. 1995;42(1):3-8. https://doi.org/10.1111/j.1365-3083.1995.tb03619.x
- 41 Goldberger AL. Is the normal heartbeat chaotic or homeostatic? News Physiol Sci. 1991;6:87-91.
- 42 Gerok W. Ordnung und Chaos als Elemente von Gesundheit und Krankheit. In: Verhandlungen d. Ges. Deutsch. Naturforscher und Ärzte. Editor. Ordnung und Chaos in der unbelebten und belebten Natur. Stuttgart: Wissenschaftl.Verlagsges; 1988. p. 19-41.
- 43 Hess B, Markus M. Chemische Uhren. In: Dress A, Hendrichs H, Küppers G, editors. Selbstorganisation: Die Entstehung von Ordnung in Natur und Gesellschaft. München: Piper; 1986. S.61
- 44 Reiber H. Epigenesis and epigenetics - understanding chronic diseases as a selforganizing stable phenotype. Neurol Psychiatry Brain Res. 2012;18(2):79-81. https://doi.org/10.1016/j.npbr.2012.02.001
- 45 Mayer H., Zaenker KS, Heiden U. A basic mathematical model of the immune response. Chaos. 1995;5(1):155-61. https://doi.org/10.1063/1.166098
- 46 Prange H, Wismann H. Intrathecal use of interferon in encephalitis. New Engl. J Med. 1981;305(21):1283-4. Https://doi.org/10.1056/NEJM198111193052113
- 47 Jupiter J, Burke D. Scott’s parabola and the rise of the medical-industrial complex. Hand (NY). 2013;8(3):249-52. https://doi.org/10.1007/s1152-013-9526-5
- 48 Reiber H. [Cerebrospinal fluid diagnostics in Germany since 1950: develepments in the GDR and FRG in the context of society and science]. Nervenarzt 2016;87(12):1261-70. German. https://doi.org/10.1007/s00115-016-0241-7