Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens

Area of Science:

• Malariology
• Immunology
• Genetics

Background:

• Hemoglobin variants like Hb AS and Hb AC are associated with reduced clinical malaria.
• Altered parasite variant surface antigen (VSA) presentation on infected erythrocytes may underlie this protection.
• The precise mechanisms linking VSA presentation, host immune response, and protection in Hb AS/AC individuals remain unclear.

Purpose of the Study:

• To investigate host serological responses to Plasmodium falciparum VSAs in Malian children with Hb AC, Hb AS, or wildtype hemoglobin (Hb AA).
• To correlate these immune responses with VSA presentation and potential protective mechanisms against malaria.

Main Methods:

• Utilized a high-throughput protein microarray to measure serological responses to various VSAs.
• Compared antibody responses to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) domains, RIFIN, and STEVOR families.
• Stratified analysis based on children's hemoglobin genotypes (Hb AC, Hb AS, Hb AA).

Main Results:

• Children with Hb AC exhibited significantly lower serological responses to extracellular PfEMP1 domains compared to Hb AA children.
• No significant differences were observed in responses to intracellular PfEMP1 domains, RIFIN, or STEVOR between Hb AC and Hb AA children.
• Healthy children with Hb AC and Hb AS genotypes recognized fewer extracellular PfEMP1s, particularly CD36-binding types, than Hb AA children.

Conclusions:

• Reduced serological responses to specific VSAs in children with Hb AC/AS may indicate decreased parasite exposure or altered VSA presentation.
• These findings offer insights into the immunological mechanisms conferring protection against clinical malaria in individuals with these hemoglobin variants.