Malaria and Systemic Lupus Erythematosus: Complex Interactions and Reciprocal Influences

Malaria, the prototypic parasitic infection, and systemic lupus erythematosus, the prototypic non-organ-specific autoimmune disease, have been linked since 1968, when it was hypothesized that malaria protected against systemic lupus erythematosus. Nitric oxide upregulation and tumour necrosis factor alpha polymorphism have been proposed as underlying factors, but a defunctioning, systemic lupus erythematosus-associated polymorphism of the low-affinity immunoglobulin gamma Fc region inhibitory receptor II-b in African and Asian populations is more likely responsible for the protective effect of malaria. Autoantibodies of specificities similar to those found in autoimmune diseases have been detected during the course of experimental murine and natural human malaria infections, and autoantibodies present in sera from patients with systemic lupus erythematosus react with native plasmodial antigens. Autoimmune responses may therefore influence the protective immunity against malaria. Finally, the repeated use of hydroxychloroquine to treat malaria may contribute to a delayed onset of systemic lupus erythematosus in people resident in endemic areas. The relations between malaria and systemic lupus erythematosus are complex, and further studies are needed to clarify interactions and reciprocal influences.