Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection.
BACKGROUND
HIV infection increases the risk of malaria infection in pregnant women. Antibodies to variant surface antigens (VSA) on infected erythrocytes might protect against malaria in pregnancy. We postulated that HIV-induced impairment of humoral immunity to VSA mediates the increased susceptibility to malaria.


METHODS
We compared serum concentrations of antibodies to VSA by flow cytometry or agglutination, and to merozoite proteins AMA-1 and MSP119 by ELISA, in 298 pregnant Malawian women, and related the findings to malaria and HIV infection, CD4-positive T-cell count, and HIV-1 viral load.


RESULTS
Concentrations of IgG to placental type VSA were lower in HIV-infected women than in HIV-uninfected women (median 8 units [IQR 4-23] vs 20 [12-30]; p<0.0001), among women with malaria (p=0.009) and those without malaria (p=0.0062). The impairment was greatest in first pregnancy. Agglutinating antibodies to placental VSA were present in a lower proportion of HIV-infected than HIV-uninfected women (58 [35.1%] of 165 vs 50 [53.8%] of 93, p<0.001). The degree of antibody binding by flow cytometry was correlated with CD4-positive T-cell count (r=0.16, p=0.019) and inversely with HIV-1 viral load (r=-0.16, p=0.030). Concentrations of antibodies to AMA-1 were lower in HIV infection (p<0.0001) but were not correlated with CD4-positive T-cell count or viral load. Responses to MSP119 were little affected by HIV infection. In multivariate analyses, HIV was negatively associated with amount of antibody to both VSA and AMA-1 (p<0.001 for each) but not MSP119.


CONCLUSIONS
HIV infection impairs antimalarial immunity, especially responses to placental type VSA. The impairment is greatest in the most immunosuppressed women and could explain the increased susceptibility to malaria seen in pregnant women with HIV infection.
Mount
Adele M
AM
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
Mwapasa
Victor
V
Elliott
Salenna R
SR
Beeson
James G
JG
Tadesse
Eyob
E
Lema
Valentino M
VM
Molyneux
Malcolm E
ME
Meshnick
Steven R
SR
Rogerson
Stephen J
SJ
D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D018791:CD4 Lymphocyte Count; D002809:Chondroitin Sulfates / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004910:Erythrocyte Membrane / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D020073:Gravidity; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016778:Malaria, Falciparum / Q000150:complications / Q000276:immunology* / Q000469:parasitology; D008565:Membrane Proteins / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D015597:Pregnancy Complications, Parasitic / Q000276:immunology; D021122:Protein Subunits / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D007074:Immunoglobulin G; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D021122:Protein Subunits; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D002809:Chondroitin Sulfates