Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

J Neuroimmunol. 2007 Feb;183(1-2):175-88. doi: 10.1016/j.jneuroim.2006.09.014. Epub 2006 Nov 16.

Abstract

Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env and disease activity was demonstrated, as were indications of a protective effect of high MBL and MASP-3 levels. The HLA alleles B*07, DRB*02, and DQB1*06 were commonly present together in the MS families, both in MS patients, and in unaffected family members. Our results support that HERV-H and the antiviral immune response may play a role in MS development, and also underline the tenuous nature of specific genetic contributions to this complex disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Complement Activation
  • Complement Pathway, Mannose-Binding Lectin / physiology*
  • Endogenous Retroviruses / immunology*
  • Environment*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Family Health
  • Female
  • Fluoroimmunoassay / methods
  • Herpesviridae / immunology*
  • Humans
  • Male
  • Mannose-Binding Lectin / metabolism
  • Mannose-Binding Lectins / metabolism
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Middle Aged
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / virology*

Substances

  • Mannose-Binding Lectin
  • Mannose-Binding Lectins
  • MASP1 protein, human
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases