Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway.
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.
Christensen
Tove
T
Institute of Medical Microbiology and Immunology, Bartholin Building, University of Aarhus, and Department of Neurology, Aarhus University Hospital, Denmark. tc@microbiology.au.dk
Petersen
Thor
T
Thiel
Steffen
S
Brudek
Tomasz
T
Ellermann-Eriksen
Svend
S
Møller-Larsen
Anné
A
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003167:Complement Activation; D037582:Complement Pathway, Mannose-Binding Lectin / Q000502:physiology*; D020077:Endogenous Retroviruses / Q000276:immunology*; D004777:Environment; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005192:Family Health; D005260:Female; D015200:Fluoroimmunoassay / Q000379:methods; D006564:Herpesviridae / Q000276:immunology*; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000821:virology*
D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins; C084067:MASP1 protein, human; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases