Introduction
Is iron harmful or helpful in MS?
1. Demonstration of an immune response to a precise autoantigen in all patients with the disease |
2. Reproduction of the lesion by administration of autoantibody or T cells into a normal animal |
3. Induction of lesion by immunizing an animal with relevant purified autoantigen |
4. Isolation or presence of autoantibody or autoreactive T cell from lesion (or serum) |
5. Correlation of autoantibody or autoreactive T cell with disease activity |
6. Presence of other autoimmune disorders or autoantigens associated with disease |
7. Immune absorption with purified autoantigen abrogates pathogenic autoantibody or autoreactive T cell |
8. Reduction of pathogenic autoantibody or T cell associated with clinical improvement |
Mind the gap
Individualised treatment for subgroups of MS?
The hypothesis of oligodendrocyte apoptosis
Iron requirement by oligodendrocytes
Iron and microglia
Iron deposits in the brain
The role of iron in the cellular antioxidant system
Iron deficiency in MS
Other requirements of oligodendrocytes
Genetics of iron metabolism in MS
Gene | Country | Study size | Association | References |
---|---|---|---|---|
SLC11A1
| South Africa | 104 MS patients, 522 controls including 32 parental alleles as family-based controls | Yes | Kotze et al. 2001
|
Spain | 195 MS patients, 125 controls | No | Comabella et al. 2004
| |
Sardinia | 66 MS patients, 60 controls | Yes | Gazouli et al. 2008
| |
Turkey | 100 MS patients, 100 controls | No | Ates et al. 2010
| |
HFE
| Tasmania | 166 MS families, 489 MS patients, 104 control families | No clinical, despite 3-fold increase of C282Y in MS | Rubio et al. 2004
|
Slovenia | 314 MS patients, 400 controls | No, although earlier onset of MS symptoms noted in C282Y carriers | Ristic et al. 2005
| |
South Africa | 118 MS patients, 102 controls | No, although two sisters with MS (without HH) were C282Y++ | Kotze et al. 2006
| |
UK | 112 benign and 51 malignant MS patients | No | ||
Portugal | 373 MS patients | No, although MS patients with mutation C282Y had a worse prognosis | Bettencourt et al. 2011
|