Journal of Neurology

, Volume 252, Issue 8, pp 968–971 | Cite as

Intrathecal antibody (IgG) production against human herpesvirus type 6 occurs in about 20% of multiple sclerosis patients and might be linked to a polyspecific B–cell response



Human herpesvirus 6 (HHV–6) is one of many infectious agents that have been implicated in the pathogenesis of multiple sclerosis (MS). Intrathecal immunoglobulin (Ig) production with oligoclonal CSF bands are hallmarks of both MS and infections of the CNS. In neuroinfections the intrathecal Ig production is directed largely against the respective agent, while MS patients mount an intrathecal Ig production against different pathogens. In this study a total of 77 serum/CSF pairs were first analyzed for an intrathecal immune response against HHV–6. We found that 21% of the MS patients, but none of the control donors showed an intrathecal immunoglobulin (Ig) response against HHV–6 (p = 0.017). Patients with such an intrathecal Ig production had a significantly higher total amount of Ig (p = 0.007) and a higher cell number in the CSF (p = 0.03). In a second step, four of the MS–patients who showed a strong intrathecal Ig production against HHV–6 were examined for immune reactivity against other viruses (human herpesvirus type 1, measles virus, human cytomegalovirus, rubella virus, varicella zoster virus). All of these patients had an intrathecal Ig production against at least one other, unrelated virus. Together, our findings strongly argue that in the majority of MS patients without an intrathecal Ig response to HHV–6 (about 80 % in our study), this virus is not involved in the pathogenesis. In the other 20% the intrathecal Ig production to HHV–6 might reflect reactivation of HHV–6 or could be part of a polyspecific B cell activation.

Key words

multiple sclerosis intrathecal immunoglobulin production HHV–6 spinal fluid 


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  1. 1.
    Ablashi DV, Lapps W, Kaplan M, Whitman JE, Richert JR, Pearson GR (1998) Human herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report. Mult Scler 4:490–496CrossRefPubMedGoogle Scholar
  2. 2.
    Alvarez-Lafuente R, De Las Heras V, Bartolome M, Picazo JJ, Arroyo R (2004) Relapsing-remitting multiple sclerosis and human herpesvirus 6 active infection. Arch Neurol 61:1523–1527CrossRefPubMedGoogle Scholar
  3. 3.
    Berti R, Brennan MB, Soldan SS, Ohayon JM, Casareto L, McFarland HF, et al. (2002) Increased detection of serum HHV-6 DNA sequences during multiple sclerosis (MS) exacerbations and correlation with parameters of MS disease progression. J Neurovirol 8:250–256 CrossRefPubMedGoogle Scholar
  4. 4.
    Challoner PB, Smith KT, Parker JD, MacLeod DL, Coulter SN, Rose TM, et al. (1995) Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci 92:7440–7444PubMedGoogle Scholar
  5. 5.
    Chapenko S, Millers A, Nora Z, Logina I, Kukaine R, Murovsk M (2003) Correlation between HHV-6 reactivation and multiple sclerosis disease activity. J Med Virol 69:111–117CrossRefPubMedGoogle Scholar
  6. 6.
    Derfuss T, Gurkov R, Then Bergh F, Goebels N, Hartmann M, Barz C, et al. (2001) Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response. Brain 124:1325–1335CrossRefPubMedGoogle Scholar
  7. 7.
    Gilden DH, Devlin ME, Burgoon MP, Owens GP (1996) The search for viruses in multiple sclerosis brain. Mult Scler 2:179–183PubMedGoogle Scholar
  8. 8.
    Goodman AD, Mock DJ, Powers JM, Baker JV, Blumberg BM (2003) Human herpesvirus 6 genome and antigen in acute multiple sclerosis lesions. J Infect Dis 187:1365–1376CrossRefPubMedGoogle Scholar
  9. 9.
    Luxton RW, Zeman A, Holzel H, Harvey P, Wilson J, Kocen R, et al. (1994) Affinity of antigen-specific IgG distinguishes multiple sclerosis from encephalitis. J Neurol Sci 132:11–19CrossRefGoogle Scholar
  10. 10.
    McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127CrossRefPubMedGoogle Scholar
  11. 11.
    Meinl E (1999) Concepts of viral pathogenesis of multiple sclerosis. Curr Opin Neurol 12:303–307CrossRefPubMedGoogle Scholar
  12. 12.
    Ongradi J, Rajda C, Marodi CL, Csiszar A, Vecsei L (1999) A pilot study on the antibodies to HHV-6 variants and HHV-7 in CSF of MS patients. J Neurovirol 5:529–532PubMedGoogle Scholar
  13. 13.
    Reiber H, Lange P (1991) Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in the brain. Clin Chem 37:1153–1160PubMedGoogle Scholar
  14. 14.
    Reiber H, Ungefaehr S, Jacobi C (1998) The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler 4:111–117CrossRefPubMedGoogle Scholar
  15. 15.
    Soldan SS, Berti R, Salem N, Secchiero P, Flamand L, Calabresi PA, et al. (1997) Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV- 6 DNA. Nat Med 3:1394–1397CrossRefPubMedGoogle Scholar
  16. 16.
    Tyler KL (2003) Human herpesvirus 6 and multiple sclerosis: the continuing conundrum. J Infect Dis 187:1360–1364CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  1. 1.Dept. of NeuroimmunologyMax–Planck–Institute of NeurobiologyMartinsriedGermany
  2. 2.Institute for Clinical NeuroimmunologyLudwig–Maximilians UniversityMunichGermany

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