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Genetic susceptibility to autoimmune disease confers resistance to severe malaria

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Michael Waisberg

on 23 March 2010

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Transcript of Genetic susceptibility to autoimmune disease confers resistance to severe malaria

Parasitemia
Body weight
Survival
Clinical data
Serum
Organs
Michael Waisberg, MD/PhD Laboratory of Immunogenetics
National Institutes of Health
National Institute of Allergy and Infectious Diseases Genetic susceptibility to autoimmune disease confers resistance to severe malaria Introduction Lupus Autoimmune disease
More common in African American women
Rare in Africa (hygiene hypothesis?)
Causes a large spectrum of manifestations
Malaria Caused by protozoans from the Plasmodium genera
Transmited by Anopheles mosquitoes
Most lethal human parasitic disease
Most common in tropical regions Kills mostly infants Strong selective pressure Malaria and Evolution thalassemia major
thalassemia minor
sickle cell disease
other haemoglobinopathies
Hypothesis Lupus protects against severe malaria The high incidence of lupus in African Americans reflects the increase in fit provided by a lupus genetic background for people living in malaria endemic areas
Models C57B6.FcγRIIb-/-.yaa
C57B6.TLR7tgs
C57B6.FcγRIIb-/-
Lupus Malaria P. berghei ANKA
P. yoelii 17XL
Causes early cerebral malaria or late severe malaria anemia Causes early severe malaria anemia Experiments Infect mice with iRBCs or through mosquito bites C57B6.FcRIIb-/-.yaa Conclusions Lupus protects against cerebral malaria
Lupus does not protect against severe malaria anemia
Protection seems to be due to a Th1 to Th2 (possibly M1/M2) shift in lupus animals
Our model suggests that the higher incidence of lupus in African Americans
could be due to malaria
Acknowledgments Susan K Pierce
Silvia Bolland
Louis Miller
Carolina Barrillas
Ken Smith Brandi Vickers
Tatyana Tarasenko
Bettany Scott
Alvaro Molina-Cruz
Robin Karstenmayer
Fernando Torres-Velles
Matthew Pierce
Lisa Willcocks






Thank you! *All 11-12 weeks old R2yaa C57B6 P. yoelii 17XL (severe anemia model) P. berghei ANKA (cerebral malaria model) P. berghei ANKA (cerebral malaria model)
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