Multiple sclerosis and anti-Plasmodium falciparum innate immune response.
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-alpha, 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.
Sotgiu
Stefano
S
Institute of Clinical Neurology, University of Sassari, Viale San Pietro, 10; I-07100, Italy. stesot@hotmail.com
Sannella
Anna R
AR
Conti
Bruno
B
Arru
Giannina
G
Fois
Maria Laura
ML
Sanna
Alessandra
A
Severini
Carlo
C
Morale
Maria Concetta
MC
Marchetti
Bianca
B
Rosati
Giulio
G
Musumeci
Salvatore
S
D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens; D006801:Humans; D007113:Immunity, Innate; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology*; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology / Q000382:microbiology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006684:HLA-DR Antigens; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha