Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens
Children with hemoglobin AC or AS have decreased susceptibility to clinical malaria. Parasite variant surface antigen (VSA) presentation on the surface of infected erythrocytes is altered in erythrocytes with hemoglobin C (Hb AC) or sickle trait (Hb AS) mutations in vitro. The protective role of incomplete or altered VSA presentation against clinical malaria in individuals with Hb AC or AS is unclear. Using a high-throughput protein microarray, we sought to use serological responses to VSAs as a measure of host exposure to VSAs among Malian children with Hb AC, Hb AS, or wildtype hemoglobin (Hb AA). In uncomplicated malaria, when compared to Hb AA children, Hb AC children had significantly lower serological responses to extracellular Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) domains but did not differ in responses to intracellular PfEMP1 domains and other VSAs, including members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family. Healthy children with Hb AC and Hb AS genotypes recognized fewer extracellular PfEMP1s compared to children with Hb AA, especially CD36-binding PfEMP1s. These reduced serologic responses may reflect reduced VSA presentation or lower parasite exposure in children with Hb AC or AS and provide insights into mechanisms of protection.
Authors
- Philip L. Felgner (ORCID: https://orcid.org/0000-0002-4117-8505)
- Shannon Takala‐Harrison (ORCID: https://orcid.org/0000-0003-4674-8500)
- Rachel D. Bailey (ORCID: https://orcid.org/0000-0002-2046-2339)
- Albert E Zhou (ORCID: https://orcid.org/0000-0003-1126-9825)
- Bourèma Kouriba (ORCID: https://orcid.org/0000-0002-3419-5972)
- Matthew B. Laurens (ORCID: https://orcid.org/0000-0003-3874-581X)
- Emily M. Stucke (ORCID: https://orcid.org/0000-0002-8256-3290)
- Mark A. Travassos (ORCID: https://orcid.org/0000-0002-6045-3322)
- Jozelyn Pablo (ORCID: https://orcid.org/0000-0002-7286-7688)
- Drissa Coulibaly (ORCID: https://orcid.org/0000-0002-7412-0940)
- Jonathan G. Lawton
- Kirsten E. Lyke (ORCID: https://orcid.org/0000-0002-4966-0830)
- Amadou Niangaly (ORCID: https://orcid.org/0000-0003-3768-8446)
- Mahamadou A. Théra (ORCID: https://orcid.org/0000-0002-2679-035X)
- Abdoulaye K. Koné (ORCID: https://orcid.org/0000-0003-4101-5391)
- Jason A. Bailey (ORCID: https://orcid.org/0000-0001-9335-2766)
- Matthew Adams (ORCID: https://orcid.org/0000-0001-7062-903X)
- Andrea A. Berry (ORCID: https://orcid.org/0000-0003-3140-3868)
- J. Alexandra Rowe (ORCID: https://orcid.org/0000-0002-7702-1892)
- Algis Jasinskas
- Ogobara K. Doumbo
- Amed Ouattara (ORCID: https://orcid.org/0000-0003-1964-7130)
- Rie Nakajima
- Dapa A. Diallo
- Christopher V. Plowe
- Aldiouma Guindo
Institutions
- University of Maryland, Baltimore (US)
- University of Bamako (ML)
- University of California, Irvine Medical Center (US)
- Université des Sciences, des Techniques et des Technologies de Bamako (ML)
- Centre for Immunity, Infection and Evolution (GB)
Publication Details
- Journal
- Journal of Infection
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1016/j.jinf.2024.106257
- Citations
- 3
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- National Institutes of Health
- School of Medicine, University of Maryland
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases