Seve
ral epidemiological investigations conducted in Sa
rdinia, insula
r Italy, indicate that the st
rong selective p
ressu
re of mala
ria along the centu
ries may have concu
rred to the elevated genetic MS-
risk in this
region. To test such hypothesis in an expe
rimental setting, we have compa
red the immune
response to
P.
falciparum (the causative agent of mala
ria) in Sa
rdinian MS patients
relative to thei
r ethnic healthy cont
rols and cont
rol MS patients of diffe
rent ethnicity. To this pu
rpose, the
P.
falciparum-d
riven pe
riphe
ral mononuclea
r cell p
rolife
ration, the p
roduction of p
ro-inflammato
ry cytokines of the innate immunity such as TNF-α, IL-6 and IL-12 and the ability to inhibit the pa
rasite g
rowth have been tested in
relation to HLA-DR alleles and TNF p
romote
r polymo
rphisms known of being associated to MS.
We found that P. falciparum-induced proliferation, cytokine production and parasite killing are significantly augmented in Sardinian MS patients as compared to controls (p < 0.01). Additionally, a correlation is found with genes associated to Sardinian MS, namely the TNF− 376A promoter polymorphism and the class II HLA-DRB10405 allele. In conclusion, we have found evidences that some genetic traits formerly selected to confer a protective responses to P. falciparum now partially contribute to the elevated MS susceptibility amongst Sardinians.
