BACKGROUND: Pregnancy-associated malaria is characterized by selection and multiplication, in the placenta, of a distinct population of Plasmodium falciparum expressing particular variant surface antigens (VSAs) that adhere to chondroitin sulfate A (CSA). METHODS: The adhesion of 40 freshly collected placental parasite isolates to bovine CSA and human placental low-sulfated chondroitin proteoglycans (CSPGs) was investigated. Plasma samples from 30 pregnant women were used to test, by flow cytometry, their recognition of and their adhesion-inhibition capacity toward 6 of these isolates. RESULTS: Adhesion to CSA and CSPGs varied between isolates but was strongly correlated between receptors (P<.001). Adhesion of isolates to receptors strongly and negatively correlated with low birth weight (LBW) of the neonate (odds ratio [95% confidence interval], 5.2 [1.1-25.1]). In plasma samples from pregnant women, the level of specific immunoglobulin G against each placental isolate (anti-VSA(PAP)) strongly correlated with the level of anti-VSA(PAP) antibodies against all other isolates (P<.05) and increased with parity in all isolates (P<.01). Conversely, adhesion-inhibitory antibodies did not correlate with isolates or with the level of anti-VSA(PAP) antibodies. CONCLUSION: The level of adhesion of placental parasites to chondroitin sulfate receptors is an important risk factor for LBW. Parasite heterogeneity suggests that they are composed of mixed adhesion phenotypes capable of inducing immune responses to a range of different and overlapping targets.
BACKGROUND: Pregnancy-associated malaria is characterized by selection and multiplication, in the placenta, of a distinct population of Plasmodium falciparum expressing particular variant surface antigens (VSAs) that adhere to chondroitin sulfate A (CSA). METHODS: The adhesion of 40 freshly collected placental parasite isolates to bovineCSA and human placental low-sulfated chondroitin proteoglycans (CSPGs) was investigated. Plasma samples from 30 pregnant women were used to test, by flow cytometry, their recognition of and their adhesion-inhibition capacity toward 6 of these isolates. RESULTS: Adhesion to CSA and CSPGs varied between isolates but was strongly correlated between receptors (P<.001). Adhesion of isolates to receptors strongly and negatively correlated with low birth weight (LBW) of the neonate (odds ratio [95% confidence interval], 5.2 [1.1-25.1]). In plasma samples from pregnant women, the level of specific immunoglobulin G against each placental isolate (anti-VSA(PAP)) strongly correlated with the level of anti-VSA(PAP) antibodies against all other isolates (P<.05) and increased with parity in all isolates (P<.01). Conversely, adhesion-inhibitory antibodies did not correlate with isolates or with the level of anti-VSA(PAP) antibodies. CONCLUSION: The level of adhesion of placental parasites to chondroitin sulfate receptors is an important risk factor for LBW. Parasite heterogeneity suggests that they are composed of mixed adhesion phenotypes capable of inducing immune responses to a range of different and overlapping targets.
Authors: Mirja Hommel; Salenna R Elliott; Viju Soma; Greg Kelly; Freya J I Fowkes; Joanne M Chesson; Michael F Duffy; Joseph Bockhorst; Marion Avril; Ivo Mueller; Andrew Raiko; Danielle I Stanisic; Stephen J Rogerson; Joseph D Smith; James G Beeson Journal: Infect Immun Date: 2010-02-16 Impact factor: 3.441
Authors: Lea Barfod; Tina Dobrilovic; Pamela Magistrado; Pongsak Khunrae; Firmine Viwami; Jonas Bruun; Madeleine Dahlbäck; Nadia L Bernasconi; Michal Fried; Davis John; Patrick E Duffy; Ali Salanti; Antonio Lanzavecchia; Chwee Teck Lim; Nicaise Tuikue Ndam; Matthew K Higgins; Lars Hviid Journal: J Immunol Date: 2010-11-15 Impact factor: 5.422
Authors: Justin Yai Alamou Doritchamou; Raul Herrera; Joan A Aebig; Robert Morrison; Vu Nguyen; Karine Reiter; Richard L Shimp; Nicholas J MacDonald; David L Narum; Michal Fried; Patrick E Duffy Journal: J Infect Dis Date: 2016-05-18 Impact factor: 5.226