The Novel Role of IgA Antibodies in the Fight Against Malaria
IgA, or immunoglobulin A antibody is well documented for its crucial role in defending against mucosally acquired pathogens. However, its specific function in immune responses to non-mucosal pathogens such as Plasmodium falciparum, the causative agent of deadly malaria, remains unclear despite IgA being the second-most abundant antibody class in the bloodstream. In recent years, scientists have increasingly focused on the role of IgA antibodies in parasitic diseases caused by Plasmodium infection, leading to promising findings.
Understanding the Role of IgA Antibodies in Malaria Defense
Malaria, caused by five types of Plasmodium species, impairs red blood cells, inducing joint pain, fever, hemolytic anemia, and increased blood protein levels. This disease is spread when a female Anopheles mosquito transfers sporozoites into the host's bloodstream during a bite. P. falciparum is the most extensively studied of the five Plasmodium species that cause infection of red blood cells because of its high incidence of disease and mortality in the human population. Studies have found that when the Malian IgA antibodies are introduced to laboratory mice infected with malaria, the parasite load in the mice decreases significantly. The researchers are able to isolate a particular monoclonal IgA antibody from individuals who show resistance to malaria. This antibody latches onto a highly conserved epitope found at the CSP protein's amino terminus, a major surface protein of the sporozoite. The findings suggest that IgA antibodies possess the capacity to combat malaria infection by specifically binding to plasmodial sporophytes. In addition, some studies have shown that the detection of Pf-specific IgA and IgM concentrations in the blood of patients can correctly judge microscopic malaria infection and predict prognosis in children. This can serve as a diagnostic indicator for the detection of malaria.
Fig.1 Levels of Pf-specific and total IgG, IgM, and IgA vary based on age and parasitemia.1
Implications for Future Malaria Treatment Strategies
On the one hand, comprehensive detection of malaria infection (including both microscopic and submicroscopic infections) in areas with high malaria prevalence is a crucial step for guiding treatment decisions and assessing prognosis. The correlation between the levels of Pf-specific IgA and IgM in patients' blood and the severity of malaria makes it a potential diagnostic marker for the disease. On the other hand, it is discovered that the body could be induced to produce circulating IgA in the presence of the sporozoites, the mobile sporocyst stage in the malaria parasite life cycle. The biological preference of IgA to target malaria parasites reflects complex behavior. Its ability to protect against pathogens, such as malaria, that mainly survive in human blood, is previously uncertain. With an alarming 200-400 million people affected by malaria annually, especially in tropical regions of the southern hemisphere and among children under five as per World Health Organization data, the identification of a new defense mechanism is significant.
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Reference
- Paloma, et al. "Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure." Frontiers in Cellular and Infection Microbiology 12 (2022): 934321. Distributed under Open Access license CC BY 4.0, without modification.
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