These three variants, like haplogroup U, were over-represented in multiple sclerosis, indicating that they reflect the same rather than different signals.
According to Lucchinetti and Brück lesions with early active demyelination reveal either of four different immunopathological subtypes of multiple sclerosis, indicating pathogenetic heterogeneity [22].
Ferritin light chain is also upregulated in circulating leukocytes of patients with juvenile rheumatoid arthritis, sickle cell disease, autoimmune renal disease or multiple sclerosis, indicating that altered FTL gene expression in peripheral cells of CAD patients might in at least in part reflect a general pro-inflammatory state that leads to degenerative changes [49] [52].
Intriguingly, various biological compounds targeting TNF resulted effective in RA treatment [32], while detrimental in multiple sclerosis [33], indicating that TNF related pathways may play a dual role in autoimmune diseases.
Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins.
This finding fits well with previous multiple sclerosis studies indicating early pathological changes in the thalamus such as atrophy, altered mean diffusivity, reduced N-acetyl-aspartate concentration and iron accumulation, whereas T2 lesions are more pronounced in the later stages of the multiple sclerosis disease (Minagar et al., 2013).
In the context of gene mapping efforts, our findings suggest a theoretically smaller number of multiple sclerosis risk genes, indicating that a greater proportion of the genes contributing to multiple sclerosis susceptibility have been identified than previously thought.
Augmented NR2F1 expression has been identified in the pre-disease state of multiple sclerosis patients, potentially indicating a role in the development of autoimmune disease [ 49].
A Th1-like bias of peripheral blood derived NKT cells was also found in diabetes [ 9] and multiple sclerosis [ 12], indicating that NKT cell dysfunction is not specific for RA but might play a major role in the aetiology of autoimmune diseases.
Although the AD brain does not present prominent infiltration of peripheral leukocytes such as those seen in other neuroinflammatory diseases (e.g., multiple sclerosis), recent studies indicate that their infiltration does occur and is stimulated by Aβ (Rezai-Zadeh et al., 2009).
