Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease
Multiple Sclerosis Journal, 04/09/2012
Perron H et al. – The association between multiple sclerosis (MS) disease and the MS associated retroviral element (MSRV)–type Human Endogenous Retroviral family ‘W’ (HERV–W) element now appears quite strong, as evidenced ex–vivo from serum and peripheral blood mononuclear cells (PBMC) with post–mortem confirmation in brain lesions. Chronic progressive MS, relapsing–remitting MS (RRMS) and clinically isolated syndrome show different ELISA (Enzyme–Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV–W elements.Methods
- 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum.
- Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR).
- Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals.
- Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01).
- Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive.
- RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001).
- In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing–remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS -<0.02).
- Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements.