TY - JOUR
T1 - Multiple sclerosis and anti-Plasmodium falciparum innate immune response
AU - Sotgiu, Stefano
AU - Sannella, Anna R.
AU - Conti, Bruno
AU - Arru, Giannina
AU - Fois, Maria Laura
AU - Sanna, Alessandra
AU - Severini, Carlo
AU - Morale, Maria Concetta
AU - Marchetti, Bianca
AU - Rosati, Giulio
AU - Musumeci, Salvatore
PY - 2007/4
Y1 - 2007/4
N2 - Several epidemiological investigations conducted in Sardinia, insular Italy, indicate that the strong selective pressure of malaria along the centuries may have concurred to the elevated genetic MS-risk in this region. To test such hypothesis in an experimental setting, we have compared the immune response to P. falciparum (the causative agent of malaria) in Sardinian MS patients relative to their ethnic healthy controls and control MS patients of different ethnicity. To this purpose, the P. falciparum-driven peripheral mononuclear cell proliferation, the production of pro-inflammatory cytokines of the innate immunity such as TNF-α, IL-6 and IL-12 and the ability to inhibit the parasite growth have been tested in relation to HLA-DR alleles and TNF promoter polymorphisms 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-DRB1*0405 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.
AB - Several epidemiological investigations conducted in Sardinia, insular Italy, indicate that the strong selective pressure of malaria along the centuries may have concurred to the elevated genetic MS-risk in this region. To test such hypothesis in an experimental setting, we have compared the immune response to P. falciparum (the causative agent of malaria) in Sardinian MS patients relative to their ethnic healthy controls and control MS patients of different ethnicity. To this purpose, the P. falciparum-driven peripheral mononuclear cell proliferation, the production of pro-inflammatory cytokines of the innate immunity such as TNF-α, IL-6 and IL-12 and the ability to inhibit the parasite growth have been tested in relation to HLA-DR alleles and TNF promoter polymorphisms 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-DRB1*0405 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.
KW - HLA
KW - Malaria
KW - Multiple sclerosis
KW - Plasmodium falciparum
KW - TNF
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U2 - 10.1016/j.jneuroim.2007.01.020
DO - 10.1016/j.jneuroim.2007.01.020
M3 - Article
C2 - 17336397
AN - SCOPUS:33947675304
VL - 185
SP - 201
EP - 207
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
IS - 1-2
ER -