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Comparative analysis of intrathecal antibody synthesis and DNA amplification for the diagnosis of cytomegalovirus infection of the central nervous system in AIDS patients

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Abstract

We evaluated 49 paired cerebrospinal fluid (CSF) and serum samples of 35 patients infected with the human immunodeficiency virus type 1 (HIV-1) for laboratory evidence of cytomegalovirus (CMV) infection. The patients were grouped according to clinical criteria as probable CMV encephalitis/polyradiculomyelitis, CMV retinitis, cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, HIV-1-related cognitive/motor complex, HIV-1-associated myelopathy, and other neurological diseases. Paired CSF and serum samples were analysed for CMV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR), quantitative intrathecal synthesis of immunoglobulin G (IgG) antibodies specific for recombinant phosphoprotein 150 (pp150) of CMV and CMV-specific serum IgM. Intrathecal synthesis of pp150-specific IgG was detected in 26% of patients (9/35), serum IgM was found in 23% of patients (8/35), and PCR of CSF was positive in 11% of patients (4/35). Detection of CMV-specific DNA in CSF preceded the intrathecal antibody synthesis in three patients for whom serial samples were available. PCR results of the CSF became negative in one patient with CMV polyradiculomyelitis after successful therapy with 9-[2-hydroxy-l(hydroxymethyl) ethoxymethyl] guanine (DHPG). PCR has a higher diagnostic specificity in the acute phase of CMV infection than intrathecal antibody synthesis. The serum IgM response to CMV cannot be used to monitor a compartmentalized immune response in the central nervous system while an intrathecal immune response seems to be associated with recovery either spontaneously or as a result of treatment.

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References

  1. Akrigg A, Wilkinson GWG, Oram JD (1985) The structure of the major immediate early gene of human cytomegalovirus strain AD 169. Virus Res 2:107–121

    Google Scholar 

  2. Anders KH, Guerra WF, Tomiyasu U, Verity MA, Vinters HV (1986) The neuropathology of AIDS. UCLA experience and review. Am J Pathol 124:537–558

    Google Scholar 

  3. Bamborschke S, Wullen T, Huber M, Neveling M, Baldamus CA, Korn K, Jahn G (1992) Early diagnosis and successful treatment of acute cytomegalovirus encephalitis in a renal transplant recipient. J Neurol 239:205–208

    Google Scholar 

  4. Borgstein BJ, Koster PA, Portegies P, Peeters FL (1989) Myelography in patients with acquired immunodeficiency syndrome. Indications and results. Neuroradiology 31:326–330

    Google Scholar 

  5. Brytting M, Xu W, Wahren B, Sundqvist V-A (1992) Cytomegalovirus DNA detection in sera from patients with active cytomegalovirus infections. J Clin Microbiol 30:1937–1941

    Google Scholar 

  6. Buffet R, Agut H, Chieze F, Katlama C, Bolgert F, Devillechabrolle A, Diquet B, Schuller E, Pierrot DC, Gentilini M, et al. (1991) Virological mark ers in the cerebrospinal fluid from HIV-1-infected individuals. AIDS 5:1419–1424

    Google Scholar 

  7. Cinque P, Vago L, Brytting M, Castagna A, Accordini A, Sundqvist VA, Zanchetta N, Monforte AD, Wahren B, Lazzarin A, Linde A (1992) Cytomegalovirus infection of the central nervous system in patients with AIDS: diagnosis by DNA amplification from cerebrospinal fluid. J Infect Dis 166:1408–1411

    Google Scholar 

  8. Dix RD, Bredesen DE, Erlich KS, Mills J (1985) Recovery of herpesviruses from cerebrospinal fluid of immunodeficient homosexual men. Ann Neurol 18:611–614

    Google Scholar 

  9. Drew WL (1988) Diagnosis of cytomegalovirus infection. Rev Infect Dis 10:S3:s468–476

    Google Scholar 

  10. Faber DW, Wiley CA, Lynn GB, Gross JG, Freeman WR (1992) Role of HIV and CMV in the pathogenesis of retinitis and retinal vasculopathy in AIDS patients. Invest Ophthalmol Vis Sci 33:2345–2353

    Google Scholar 

  11. Gans J de, Portegies P, Tiessens G, Troost D, Danner SA, Lange JM (1990) Therapy for cytomegalovirus polyradiculomyelitis in patients with AIDS: treatment with ganciclovir. AIDS 4:421–425

    Google Scholar 

  12. Gans J de, Tiessens G, Portegies P, Tutarima JA, Troost D (1990) Predominance of polymorphonuclear leukocytes in cerebrospinal fluid of AIDS patients with cytomegalovirus polyradiculomyelitis. J Acquir Immune Defic Syndr 3:1155–1158

    Google Scholar 

  13. Gøtzsche PC, Bygbjerg IC, Olesen B, Møller LH, Salim YS, Faber V (1988) Yield of diagnostic tests for opportunistic infections in AIDS: a survey of 33 patients. Scand J Infect Dis 20:395–402

    Google Scholar 

  14. Gozlan J, Salord JM, Roullet E, Baudrimont M, Caburet F, Picard O, Meychas MC, Duvivier C, Jacomet C, Petit JC (1992) Rapid detection of cytomegalovirus DNA in cerebrospinal fluid of AIDS patients with neurologic disorders. J Infect Dis 166:1416–1421

    Google Scholar 

  15. Grafe MR, Wiley CA (1989) Spinal cord and peripheral nerve pathology in AIDS: the roles of cytomegalovirus and human immunodeficiency virus. Ann Neurol 25:561–566

    Google Scholar 

  16. Gray F, Gherardi R, Scaravilli F (1988) The neuropathology of the acquired immune deficiency syndrome (AIDS). A review. Brain 111:245–266

    Google Scholar 

  17. Gross JG, Bozzette SA, Mathews WC, Spector SA, Abramson IS, McCutchan JA, Mendez T, Munguia D, Freeman WR (1990) Longitudinal study of cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmology 97:681–686

    Google Scholar 

  18. Jarvik JG, Hesselink JR, Kennedy C, Teschke R, Wiley C, Spector S, Richman D, McCutchan JA (1988) Acquired immunodeficiency syndrome. Magnetic resonance patterns of brain involvement with pathologic correlation. Arch Neurol 45:731–736

    Google Scholar 

  19. Kure K, Llena IF, Lyman WD, Soeiro R, Weidenheim KM, Hirano A, Dickson DW (1991) Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains. Hum Pathol 22:700–710

    Google Scholar 

  20. Kwok S, Higuchi R (1989) Avoiding false positives with PCR. Nature 339:237–238

    Google Scholar 

  21. Lang W, Miklossy J, Deruaz JP, Pizzolato GP, Probst A, Schaffner T, Gessaga E, Kleihues P (1989) Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland. Acta Neuropathol (Berl) 77:379–390

    Google Scholar 

  22. Levy RM, Pons VG, Rosenblum ML (1984) Central nervous system mass lesions in the acquired immunodeficiency syndrome (AIDS). J Neurosurg 61:9–16

    Google Scholar 

  23. Lüer W, Gerhards J, Poser S, Weber T, Felgenhauer K (1994) Acute diffuse leukoencephalitis in HIV-1 infection. J Neurol Neurosurg Psychiatry (in press)

  24. Marmaduke DP, Brandt JT, Theil KS (1991) Rapid diagnosis of cytomegalovirus in the cerebrospinal fluid of a patient with AIDS-associated polyradiculopathy. Arch Pathol Lab Med 115:1154–1157

    Google Scholar 

  25. McKenzie R, Travis WD, Dolan SA, Pittaluga S, Feuerstein IM, Shelhamer J, Yarchoan R, Masur H (1991) The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases. Medicine (Baltimore) 70:326–343

    Google Scholar 

  26. Morgello S, Cho ES, Nielsen S, Devinsky O, Petito CK (1987) Cytomegalovirus encephalitis in patients with acquired immunodeficiency syndrome: an autopsy study of 30 cases and a review of the literature. Hum Pathol 18:289–297

    Google Scholar 

  27. Oldstone MB, Blount P, Southern PJ, Lampert PW (1986) Cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system. Nature 321:239–243

    Google Scholar 

  28. Porter SB, Sande MA (1992) Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med 327:1643–1648

    Google Scholar 

  29. Post MJ, Hensley GT, Moskowitz LB, Fischl M (1986) Cytomegalic inclusion virus encephalitis in patients with AIDS: CT, clinical, and pathologic correlation. Am J Roentgenol 146:1229–1234

    Google Scholar 

  30. Potasman I, Resnick L, Luft BJ, Remington IS (1988) Intrathecal production of antibodies against Toxoplasma gondii in patients with toxoplasmic encephalitis and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 108:49–51

    Google Scholar 

  31. Reiber H, Felgenhauer K (1987) Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 163:319–328

    Google Scholar 

  32. Reiber H, Lange P (1991) Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem 37:1153–1160

    Google Scholar 

  33. Report of a working group of the American Academy of Neurology AIDS Task Force (1991) Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV1) infection. Neurology 41:778–785

    Google Scholar 

  34. Rüger B, Klages S, Walla B, Albrecht J, Fleckenstein B, Tomlinson B, Bartell BG (1987) Primary structure and transcription of the genes coding the two virion phosphoproteins pp65 and pp71 of human Cyomegalovirus. J Virol 61:446–453

    Google Scholar 

  35. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491

    Google Scholar 

  36. Sambrook J, Fritsch EF, Maniatis T (1989) Preparation of radiolabeled DNA and RNA probes. In: Sambrook J, Fritsch EF, Maniatis T (eds) Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 10.1–10.70

    Google Scholar 

  37. Schmidbauer M, Budka H, Ulrich W, Ambros P (1989) Cytomegalovirus (CMV) disease of the brain in AIDS and connatal infection: a comparative study by histology, immunocytochemistry and in situ DNA hybridization [erratum appeared inActa Neuropathol (Berl) (1990) 79:579]. Acta Neuropathol (Berl) 79:286–293

    Google Scholar 

  38. Smith E, Pers C, Aschow C, Mathiesen L (1991) Cerebral toxoplasmosis in Danish AIDS patients. Scand J Infect Dis 23:703–709

    Google Scholar 

  39. Snow RB, Lavyne MH (1985) Intracranial space-occupying lesions in acquired immune deficiency syndrome patients. Neurosurgery 16:148–153

    Google Scholar 

  40. Spector SA, Merril R, Wolf D, Dankner WM (1992) Detection of human cytornegalovirus in plasma of AIDS patients during acute visceral disease by DNA amplification. J Clin Microbiol 30:2359–2365

    Google Scholar 

  41. Vinters HV, Kwok MK, Ho HW, Anders KH, Tomiyasu U, Wolfson WL, Robert F (1989) Cytomegalovirus in the nervous system of patients with the acquired immune deficiency syndrome. Brain 112:245–268

    Google Scholar 

  42. Weber T, Freter A, Luer W, Haas J, Stark E, Poser S, Felgenhauer K (1991) The use of recombinant antigens in ELISA procedures for the quantification of intrathecally produced HIV-1-specific antibodies. J Immunol Methods 136:133–137

    Google Scholar 

  43. Wiley CA, Nelson JA (1988) Role of human immunodeficiency virus and cytornegalovirus in AIDS encephalitis. Am J Pathol 133:73–81

    Google Scholar 

  44. Wolf DG, Spector SA (1992) Diagnosis of human cytornegalovirus central nervous system disease in AIDS patients by DNA amplification from cerebrospinal fluid. J Infect Dis 166:1412–1415

    Google Scholar 

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Author information

Author notes

  1. G. Jahn

    Present address: Institut für Virologie, Eberhard-Karls-Universität Tübingen, Silcher Strasse 7, D-72076, Tübingen, Germany

  2. J. Haas

    Present address: Klinik für Neurologie und Psychiatrie, Medizinische Akademie, Leipziger Strasse 44, D-39120, Magdeburg, Germany

Authors and Affiliations

  1. Neurologische Klinik und Poliklinik, Georg-August-Universität Göttingen, Robert-Koch-Strasse 40, D-37075, Göttingen, Germany

    T. Weber, J. Gerhards & W. Lüer

  2. Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universiät Erlangen-Nürnberg, Loschgestrasse 7, D-91054, Erlangen, Germany

    R. Beck, K. Korn & G. Jahn

  3. Department of Neurology, Medizinische Hochschule Hannover, Konstanty-Gutschow-Strasse, D-30625, Hannover, Germany

    E. Stark & J. Haas

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  1. T. Weber
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Weber, T., Beck, R., Stark, E. et al. Comparative analysis of intrathecal antibody synthesis and DNA amplification for the diagnosis of cytomegalovirus infection of the central nervous system in AIDS patients. J Neurol 241, 407–414 (1994). https://doi.org/10.1007/BF00900957

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  • DOI: https://doi.org/10.1007/BF00900957

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