Skip to main content

Advertisement

SpringerLink
Log in

Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher’s exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47–74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50–84) mg/L, in comparison to those who remained NAb-negative, 83 (68–107) mg/L, P = 0.03, and 76 (66–87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04–0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3–87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hartung HP, Polman C, Bertolotto A et al (2007) Neutralising antibodies to interferon β in multiple sclerosis: expert panel report. J Neurol 254:827–837

    Article  CAS  PubMed  Google Scholar 

  2. Bendtzen K, Kromminga A (2008) Immunogenicity of interferon-beta. In: van de Weert M, Moller EH (eds) Biotechnology: pharmaceutical aspects vol VIII. Immunogenicity of biopharmaceuticals. Springer, New York, pp 127–136

    Google Scholar 

  3. Hoffmann S, Cepok S, Grummel V et al (2008) HLA-DRB1*0401 and HLA-DRB1 *0408 are strongly associated with the development of antibodies against interferon-β therapy in multiple sclerosis. Am J Hum Genet 83:219–227

    Article  CAS  PubMed  Google Scholar 

  4. Gilli F, Valentino P, Caldano M (2008) Expression and regulation of IFNalpha/beta receptor in IFNbeta-treated patients with multiple sclerosis. Neurology 71:1940–1947

    Article  CAS  PubMed  Google Scholar 

  5. Lo JC, Wang Y, Tumanov AV et al (2007) Lymphotoxin alpha receptor-dependent control of lipid homeostasis. Science 316:285–288

    Article  CAS  PubMed  Google Scholar 

  6. Getz SG, Reardon CA (2009) Apoprotein E as a lipid transport and signalling protein in the blood, liver, and artery wall. J Lipid Res S156–S161

  7. Giubilei F, Antonini G, De Legges S et al (2002) Blood cholesterol and MRI activity in first episode suggestive of multiple sclerosis. Acta Neurol Scand 106:109–112

    Article  CAS  PubMed  Google Scholar 

  8. Jamroz-Wisniewska A, Beltowski J, Stelmasiak Z, Bartosik-Psujek H (2009) Paraoxonase 1 activity in different types of multiple sclerosis. Mult Scler 15:399–402

    Article  CAS  PubMed  Google Scholar 

  9. McDonald WI, Compston A, Edan G et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on diagnosis of multiple sclerosis. Ann Neurol 50:121–127

    Article  CAS  PubMed  Google Scholar 

  10. Kurtzke JF (1983) Rating neurological impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    CAS  PubMed  Google Scholar 

  11. Roxburgh RH, Seaman SR, Masterman T et al (2005) Multiple sclerosis severity score: using disability and disease duration to rate disease severity. Neurology 64:1144–1151

    CAS  PubMed  Google Scholar 

  12. Rio J, Nos C, Tintoré M et al (2006) Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients. Ann Neurol 59:344–352

    Article  CAS  PubMed  Google Scholar 

  13. Sorensen PS, Ross C, Clemmesen KM et al (2003) Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 362:1184–1191

    Article  CAS  PubMed  Google Scholar 

  14. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  PubMed  Google Scholar 

  15. Sena A, Couderc Ferret-SenaV et al (2009) Apolipoprotein E polymorphism interacts with cigarette smoking in progression of multiple sclerosis. Eur J Neurol l16:832–837

    Article  Google Scholar 

  16. Comabella M, Lunemann JD, Rio J et al (2009) A type I interferon signature in monocytes associated with poor response to interferon-beta in multiple sclerosis. Brain 132:3353–3365

    Article  CAS  PubMed  Google Scholar 

  17. Carlsson J, Armstrong VW, Reiber H et al (1991) Clinical relevance of the quantification of apolipoprotein E in cerebrospinal fluid. Clin Chem Acta 196:167–176

    Article  CAS  Google Scholar 

  18. Feng-Qiao L, Sempowski GD, McKenna SE et al (2006) Apolipoprotein E-derived peptides ameliorate clinical disability and inflammatory infiltrates into the spinal cord in murine model of multiple sclerosis. J Pharmacol Exp Ther 318:956–965

    Article  Google Scholar 

  19. Li L, Thompson PA, Kitchens RL (2008) Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors. J Lipid Res 49:1782–1793

    Article  CAS  PubMed  Google Scholar 

  20. Garg N, Weinstock-Guttman B, Bhasi K, Locke J, Ramanathan M (2007) An association between autoreactive antibodies and anti-interferon-β antibodies in multiple sclerosis. Mult Scler 13:895–899

    Article  CAS  PubMed  Google Scholar 

  21. Sena A, Pedrosa R, Graça Morais M (2004) Statins for multiple sclerosis. Lancet 364:412

    Article  PubMed  Google Scholar 

  22. Sapori M (2002) Effects of cigarette smoke on the immune system. Nat Rev Immunol 2:372–377

    Article  Google Scholar 

Download references

Acknowledgments

We thank nurses Cristina Araújo and Ana Mendes, and Mrs Firmina Lebre and Augusta Marques for help in research. We are also grateful to BioEPI, Clinical and Translational Research Centre, for assistance in statistical analysis by Dr. Joana Vasconcelos and for epidemiological revision by Dr. Elizabeth Benito-Garcia. This work was supported by a grant from Biogen idec Portugal (RECONVERT project).

Author information

Authors and Affiliations

  1. CEDOC, Departamento de Bioquímica, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

    Armando Sena, Maria J. Cascais & Elisa Campos

  2. Departamento de Neurociências, Centro Hospitalar de Lisboa-Central, Lisbon, Portugal

    Armando Sena & Rui Pedrosa

  3. Institute for Inflammation Research IIR7521, Rigshospitalet National University Hospital, Copenhagen, Denmark

    Klaus Bendtzen

  4. Departamento de Fisiologia, Centro de Investigação Interdisciplinar Egas Moniz, Monte de Caparica, Portugal

    Véronique Ferret-Sena

Authors
  1. Armando Sena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Bendtzen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria J. Cascais
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rui Pedrosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Véronique Ferret-Sena
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elisa Campos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Armando Sena.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sena, A., Bendtzen, K., Cascais, M.J. et al. Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta. J Neurol 257, 1703–1707 (2010). https://doi.org/10.1007/s00415-010-5606-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-010-5606-4

Keywords

Search

Navigation