Identification of a 67‐amino‐acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates
Open accessAbstract
Summary: The complications of malaria in pregnancy are caused by the massive sequestration of parasitized erythrocytes (PE) in the placenta. Placental isolates of Plasmodium falciparum are unusual in that they do not bind the primary microvasculature receptor CD36 but instead bind chondroitin sulphate A (CSA). Pregnant mothers develop antibodies that recognize placental variants worldwide, suggesting that a vaccine against malaria in pregnancy is possible. Some members of the Duffy binding‐like γ (DBL‐γ) domain of the large and diverse P. falciparum erythrocyte membrane protein‐1 (PfEMP‐1) family, when expressed on Chinese hamster ovary (CHO) cells, bind CSA. To characterize better the molecular requirements for DBL‐γ adhesion to CSA, we determined the binding of various DBL‐γ domains. Most DBL‐γ did not bind CSA, and no conserved region was identified that strictly differentiated binders from non‐binders. Structure–function analysis of the FCR3‐CSA DBL‐γ domain localized the minimal CSA binding region to a 67‐residue fragment. This region was partially conserved among some binding sequences. Serum from a rabbit immunized with the minimal domain reacted with CSA‐binding parasite lines, but not with non‐CSA‐adherent PE lines that adhered to CD36 and other receptors. The identification of a minimal binding region from a highly variable cytoadherent family may have application for a vaccine against malaria in pregnancy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The presence of CSA-binding domains that can be inhibited by specific IgG or CSA in itself is not sufficient evidence for involvement in the pathogenesis of PAM.
“Therefore, the presence of CSA-binding domains that can be inhibited by specific IgG or CSA in itself is not sufficient evidence for involvement in the pathogenesis of PAM (29).”
From Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria (2004) · cites this paper as [29]
Cites
Su, X.-Z., Heatwole, V. M., Wertheimer, S. P., Guinet, F., Herrfeldt, J. A., Peterson, D. S., Ravetch, J. A., & Wellems, T. E. (1995) · Cell · doi:10.1016/0092-8674(95)90055-1 · Cited by 1,219 · see citing works
Adherence of <i>Plasmodium falciparum</i> to Chondroitin Sulfate A in the Human Placenta
Fried, M., & Duffy, P. E. (1996) · Science · doi:10.1126/science.272.5267.1502 · Cited by 1,108 · see citing works
Plasmodium falciparum adhesion in the placenta
Duffy, P. E., & Fried, M. (2003) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(03)00090-0 · Cited by 73 · cited 1× · see citing works
“Placental sequestration affects both mother and fetus (Menendez, 1995; Duffy, 2003; Duffy and Fried, 2003) but, until recently, it was not clear why high parasitaemia infections occurred in pregnant women who otherwise possess significant clinical immunity to malaria.”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria
Salanti, A., Dahlbäck, M., Turner, L., Nielsen, M. A., Barfod, L., Magistrado, P., Jensen, A. T. R., Lavstsen, T., Ofori, M. F., Marsh, K., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041579 · Cited by 604 · see citing works
Viebig, N. K., Gamain, B., Scheidig, C., Lépolard, C., Przyborski, J., Lanzer, M., Gysin, J., & Scherf, A. (2005) · The EMBO Reports · doi:10.1038/sj.embor.7400466 · Cited by 201 · see citing works
Self-citationGamain, B., Trimnell, A. R., Scheidig, C., Scherf, A., Miller, L. H., & Smith, J. D. (2005) · The Journal of Infectious Diseases · doi:10.1086/428137 · Cited by 145 · see citing works
Self-citationBarfod, L., Bernasconi, N. L., Dahlbäck, M., Jarrossay, D., Andersen, P. H., Salanti, A., Ofori, M. F., Turner, L., Resende, M., Nielsen, M. A., et al. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05503.x · Cited by 110 · see citing works
Singh, K., Gittis, A. G., Nguyen, P., Gowda, D. C., Miller, L. H., & Garboczi, D. N. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1479 · Cited by 99 · see citing works
Self-citationCharacterization of anti-var2CSA-PfEMP1 cytoadhesion inhibitory mouse monoclonal antibodies
Avril, M., Gamain, B., Lépolard, C., Viaud, N., Scherf, A., & Gysin, J. (2006) · Microbes and Infection · doi:10.1016/j.micinf.2006.09.005 · Cited by 61 · see citing works
Self-citationBrolin, K. J. M., Persson, K. E. M., Wahlgren, M., Rogerson, S. J., & Chen, Q. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009230 · Cited by 24 · see citing works
“shown to contain a 12-mer residue deletion and did not bind CSA [33].”
BackgroundIyamu, U., Vinals, D. F., Tornyigah, B., Arango, E., Bhat, R., Adra, T. R., Grewal, S., Martin, K., Maestre, A., Overduin, M., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1202276 · Cited by 7 · see citing works
- Authors
- Gamain, B., Smith, J. D., Avril, M., Baruch, D. I., Scherf, A., Gysin, J., & Miller, L. H.
- Affiliations
- Center for Infectious Disease Research (US)
- Université de la Méditerranée Aix-Marseille II (FR)
- National Institutes of Health (US)
- Institut Pasteur (FR)
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2004-06-04
- Volume
- 53
- Issue
- 2
- Pages
- 445-455
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2100457133
- Cited by
- 40
- References
- 3
- Citations by year
- 2023: 1 · 2015: 1 · 2014: 1 · 2012: 1
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- European Commission
- National Institutes of Health (RO1 AI47953)
- National Institute of Allergy and Infectious Diseases (R01 AI4795301A1)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- Plasmodium falciparum, variant surface antigens, PfEMP1, chondroitin sulfate A, placental malaria, malaria in pregnancy, parasite adhesion, CD36, vaccine candidate, antibody response, cytoadherence
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Protozoan, Antigens, Protozoan, Cell Adhesion, Cell Line, Chondroitin Sulfates, Cricetinae, Membrane Proteins, Phylogeny, Plasmodium falciparum, Protein Binding, Rabbits, Structure-Activity Relationship, Protozoan Proteins, Conserved Sequence, Sequence Homology, Protein Structure, Tertiary, CD36 Antigens
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
