Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both
in terms of predisposition to the disease and of immunological mechanisms which are
known to play crucial roles in MS pathogenesis. The presence of high- and low-risk
areas for MS in neighbouring regions supports the theory that MS predisposition is
influenced by a complex interaction of genetic and environmental factors. Therefore,
the use of genetically homogeneous and geographically isolated populations becomes
an increasing requirement to reduce biasing biological variables. Sardinians fulfil these
conditions well because of their different phylogeny from Europeans and the unique
selective pressures which shaped their genome. Sardinians display amongst the highest
MS prevalence rates world-wide and increasing MS incidence rates over time. Also,
MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and
associated to different patterns of cytokine production from lymphoid cells of different
HLA subtypes. In this context, recent findings and future perspectives on the
peculiarities of Sardinian MS concerning genetic, immunological and epidemiological
aspects are presented. So far, our results indicate that variations at the level of
territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population