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Clinical Chemistry, Vol 37, 1153-1160, Copyright © 1991 by American Association for Clinical Chemistry
H Reiber and P Lange
Neurochemisches Labor der Neurologischen Klinik, Universitat Gottingen, F.R.G.
Specific antibody synthesis in brain could be detected with maximal sensitivity by combining an advanced enzyme immunoassay with a sophisticated evaluation method that involves calculating the ratio between the cerebrospinal fluid (CSF)/serum quotients for specific antibodies (Qspec) and total IgG (QIgG). This Antibody Index (AI = Qspec/QIgG) discriminates between a blood-derived and a pathological, brain-derived specific antibody fraction in CSF and takes into account individual changes in blood/CSF barrier function. For local synthesis of polyclonal IgG in the central nervous system (QIgG greater than QLim), we propose the correction AI = Qspec/QLim (QLim represents that IgG fraction in CSF originating only from blood, calculated from the individual albumin quotient of a single patient). The normal reference range for the AI was between 0.7 and 1.3 (n = 250 control patients for each antibody species). Values of AI greater than or equal to 1.5 indicated a local specific antibody synthesis in the central nervous system. Sensitivity and precision were greatest if we analyzed the virus-specific antibodies in CSF and serum simultaneously with an enzyme immunoassay in continuous concentrations (arbitrary units) instead of titer steps. We have applied the method successfully to antibodies to measles, rubella, herpes simplex, varicella-zoster, human immunodeficiency virus (HIV), and cytomegalovirus, and to anti- Toxoplasma or -Borrelia antibodies. Clinical relevance is demonstrated for an acute zoster virus infection (monospecific response), chronic diseases such as HIV encephalitis with acute opportunistic Toxoplasma infection, and multiple sclerosis (secondary polyspecific response).
The following articles in journals at HighWire Press have cited this article:
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  M. Puccioni-Sohler, C. N. Soares, R. Papaiz-Alvarenga, M.J.C. Castro, L. C. Faria, and J. M. Peralta Neurologic dengue manifestations associated with intrathecal specific immune response Neurology, October 27, 2009; 73(17): 1413 - 1417. [Abstract] [Full Text] [PDF]
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 T. Derfuss, K. Parikh, S. Velhin, M. Braun, E. Mathey, M. Krumbholz, T. Kumpfel, A. Moldenhauer, C. Rader, P. Sonderegger, et al. From the Cover: Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals PNAS, May 19, 2009; 106(20): 8302 - 8307. [Abstract] [Full Text] [PDF]
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D. T. Blumenthal, K. L. Salzman, J. R. Baringer, B. Forghani, and D. H. Gilden MRI abnormalities in chronic active varicella zoster infection Neurology, October 26, 2004; 63(8): 1538 - 1539. [Full Text] [PDF]
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 A. N. Russman, R. J. Lederman, L. H. Calabrese, P. J. Embi, B. Forghani, and D. H. Gilden Multifocal Varicella-Zoster Virus Vasculopathy Without Rash Arch Neurol, November 1, 2003; 60(11): 1607 - 1609. [Abstract] [Full Text] [PDF]
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K. Rostasy, H. Reiber, D. Pohl, P. Lange, A. Ohlenbusch, H. Eiffert, M. Maass, and F. Hanefeld Chlamydia pneumoniae in children with MS: Frequency and quantity of intrathecal antibodies Neurology, July 8, 2003; 61(1): 125 - 128. [Abstract] [Full Text] [PDF]
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 A. Regeniter, J. U. Steiger, A. Scholer, P. R. Huber, and W. H. Siede Windows to the Ward: Graphically Oriented Report Forms. Presentation of Complex, Interrelated Laboratory Data for Electrophoresis/Immunofixation, Cerebrospinal Fluid, and Urinary Protein Profiles Clin. Chem., January 1, 2003; 49(1): 41 - 50. [Abstract] [Full Text] [PDF]
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 D. H. Gilden, H. L. Lipton, J. S. Wolf, W. Akenbrandt, J. E. Smith, R. Mahalingam, and B. Forghani Two Patients with Unusual Forms of Varicella-Zoster Virus Vasculopathy N. Engl. J. Med., November 7, 2002; 347(19): 1500 - 1503. [Full Text] [PDF]
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 R K Garg Subacute sclerosing panencephalitis Postgrad. Med. J., February 1, 2002; 78(916): 63 - 70. [Abstract] [Full Text] [PDF]
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 A. Majid, S. L. Galetta, C. J. Sweeney, C. Robinson, R. Mahalingam, J. Smith, B. Forghani, and D. H. Gilden Epstein-Barr virus myeloradiculitis and encephalomyeloradiculitis Brain, January 1, 2002; 125(1): 159 - 165. [Abstract] [Full Text] [PDF]
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R.J. Fox, S.L. Galetta, R. Mahalingam, M. Wellish, B. Forghani, and D.H. Gilden Acute, chronic, and recurrent varicella zoster virus neuropathy without zoster rash Neurology, July 24, 2001; 57(2): 351 - 354. [Abstract] [Full Text] [PDF]
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T. Derfuss, R. Gurkov, F. Then Bergh, N. Goebels, M. Hartmann, C. Barz, B. Wilske, I. Autenrieth, M. Wick, R. Hohlfeld, et al. Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response Brain, July 1, 2001; 124(7): 1325 - 1335. [Abstract] [Full Text] [PDF]
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 R. KAISER False-negative serology in patients with neuroborreliosis and the value of employing of different borrelial strains in serological assays J. Med. Microbiol., October 1, 2000; 49(10): 911 - 915. [Abstract] [Full Text] [PDF]
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 M. Wilke, H. Eiffert, H.-J. Christen, and F. Hanefeld Primarily chronic and cerebrovascular course of Lyme neuroborreliosis: case reports and literature review Arch. Dis. Child., July 1, 2000; 83(1): 67 - 71. [Abstract] [Full Text]
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W. I. Rosenblum and R. Nau Varicella zoster virus-associated focal vasculitis without herpes zoster Neurology, July 1, 1999; 53(1): 239 - 239. [Full Text]
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 H. Reiber Cerebrospinal fluid - physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases Multiple Sclerosis, June 1, 1998; 4(3): 99 - 107. [Abstract] [PDF]
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H Reiber, S Ungefehr, and C. Jacobi The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis Multiple Sclerosis, June 1, 1998; 4(3): 111 - 117. [Abstract] [PDF]
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J. L Frederiksen and C. J. Sindic Intrathecal synthesis of virus-specific oligoclonal IgG, and of free kappa and free lambda oligoclonal bands in acute monosymptomatic optic neuritis. Comparison with brain MRI Multiple Sclerosis, February 1, 1998; 4(1): 22 - 26. [Abstract] [PDF]
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 G. C. Korenke, H. Reiber, D. H. Hunneman, and F. Hanefeld Inthrathecal IgA Synthesis in X-Linked Cerebral Adrenoleukodystrophy J Child Neurol, August 1, 1997; 12(5): 314 - 320. [Abstract] [PDF]
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