# Kinetics of antimalarial antibodies in children with common haemoglobinopathies in a Tanzanian population

## TL;DR

This study explores how common blood disorders affect antibody responses to malaria in Tanzanian children, shedding light on how these conditions may protect against the disease.

## Contribution

The study reveals distinct antibody associations with α+-thalassaemia and sickle cell trait, offering new insights into their protective mechanisms against malaria.

## Key findings

- Antibody levels to MSP3 and Group B PfEMP1 showed opposing associations with α+-thalassaemia and sickle cell trait.
- Sickle cell trait may reduce adhesion of malaria-infected cells to blood vessels, while α+-thalassaemia may hinder parasite invasion.
- The findings clarify how haemoglobinopathies influence immune responses and malaria protection.

## Abstract

Haemoglobin gene mutations have long been associated with protection against malaria, as evidenced by the concordant geographic distribution of these mutations with malaria parasite prevalence and by the reduced risk of severe disease among individuals carrying thalassaemia or sickle cell trait alleles. However, the mechanisms underlying this protection remain poorly understood. Although the precise correlates of immunity to malaria are still debated, antibody-mediated responses are widely considered to play a critical role. In this study, we investigated changes in putatively protective anti-malarial antibody titres in relation to age, malaria infection, and protection in Tanzanian children with and without α+-thalassaemia.

Antibody responses were quantified using a multiplex assay targeting sporozoite antigens (CSP), merozoite antigens (AMA1, MSP119, MSP3, GLURP R0 and R2), and infected red blood cell surface antigens (PfEMP1 groups A, B, and E). A linear mixed-effects modelling framework, assuming a multivariate normal distribution of residuals, was applied to determine whether antibody responses to specific antigens or antigen groups differed by haemoglobinopathy status or were associated with protection from malaria.

In age-adjusted analyses, antibody levels to MSP3 and Group B PfEMP1 exhibited opposing associations with inherited red blood cell disorders: responses were negatively associated with α+-thalassaemia and positively associated with sickle cell trait, respectively.

These findings suggest that sickle cell trait may modulate PfEMP1 expression, thereby weakening the adhesion of Plasmodium falciparum–infected red blood cells to microvascular endothelial cells, while α⁺-thalassaemia may interfere with the shedding of parasite surface proteins involved in erythrocyte invasion. Collectively, these results provide further insight into the immunological and cellular mechanisms by which haemoglobinopathies confer protection against malaria.