Turf wars: exploring splenomegaly in sickle cell disease in malaria-endemic regions

Abstract

Sickle cell disease (SCD) is a group of recessively inherited disorders of erythrocyte function that presents an ongoing threat to reducing childhood and adult morbidity and mortality around the world. While decades of research have led to improved survival for SCD patients in wealthy countries, survival remains dismal in low- and middle-income countries. Much of the early mortality associated with SCD is attributed to increased risk of infections due to early loss of splenic function. In the West, bacterial infections with encapsulated organisms are a primary concern. In sub-Saharan Africa, where the majority of infants with SCD are born, the same is true. However malaria presents an additional threat to survival. The search for factors that define variability in sickle cell phenotypes should include environmental modifiers, such as malaria. Further exploration of this relationship could lead to novel strategies to reduce morbidity and mortality attributable to infections. In this review, we explore the interactions between SCD, malaria and the spleen to better understand how splenomegaly and splenic (dys)function may co-exist in patients with SCD living in malaria-endemic areas.

Keywords: immune function; malaria; marginal zone B cell; sickle cell disease; spleen.

Figure 1. Architecture of the spleen

Blood enters the spleen through the afferent splenic artery and is directed either to the periarteriolar lymphoid sheath and follicles, or to the red pulp and sinuses. Antigen-presenting cells interact with phagocytic cells and lymphocytes to mount humoral and innate responses to malaria. Figure adapted by permission from Macmillan Publishers Ltd: Nat Rev Immunol, Mebius, R. E., Kraal, G. Structure and function of the spleen. 5, 606–616, ©2005

Figure 2. Histopathology of the spleen from patients with sickle cell disease

(A) In normal spleen tissue, the follicle is organized into germinal centre (GC), mantle zone (Mn) and marginal zone (MZ).Senescent red cells are trapped and destroyed in the surrounding red pulp. (B) In a US patient with SCD who was splenectomised following recovery from splenic sequestration, the red pulp is congested with sickled cells. The structure of the follicle is less well defined. (C) An African patient with SCD who was splenectomised for splenic sequestration demonstrates congested of red pulp and preserved follicular architecture. (D) An African SCD patient who was splenectomised for hypersplenism similarly demonstrates engulfment of red pulp and preserved follicular architecture. In this patient, haemozoin deposits (E, solid arrowhead) and gamna gandy bodies are prominent (E and F, open arrowhead). All images are stained with haematoxylin and eosin stain. Magnification: 10x.