Neutrophil dysfunctions in sickle cell disease

Area of Science:

• Hematology
• Immunology
• Infectious Diseases

Background:

• Sickle cell disease (SCD) patients exhibit abnormal susceptibility to infections, partly due to spleen and complement pathway defects.
• Fulminant childhood infections with encapsulated organisms are linked to these known defects.
• Frequent systemic infections with enteric organisms and Staphylococcus aureus in SCD are less understood.

Purpose of the Study:

• To investigate the role of neutrophil (PMN) dysfunctions in the increased infection tendency observed in SCD patients.
• To present previously unpublished laboratory data regarding PMN function in SCD.
• To develop a working hypothesis explaining infection susceptibility in SCD.

Main Methods:

• Review of existing literature on SCD and infection susceptibility.
• Analysis of laboratory data on neutrophil function, including locomotion, phagocytosis, and bactericidal activity.
• Examination of potential contributing factors such as serum abnormalities and leukocyte demargination.

Main Results:

• Neutrophil dysfunctions identified include decreased chemotaxis, impaired in vivo migration, and reduced phagocytic processes.
• Bactericidal defects were observed against Staphylococcus aureus, Candida albicans, and Streptococcus pneumoniae, linked to poor oxidative activity.
• Salmonella species may further impair PMN oxidative machinery in SCD patients.
• Serum abnormalities and dysfunctional PMNs, possibly originating from functional asplenia, contribute to increased infection risk.

Conclusions:

• Neutrophil dysfunctions significantly contribute to the heightened susceptibility to infections in SCD patients.
• Impaired neutrophil locomotion, phagocytosis, and particularly bactericidal activity due to oxidative defects are key factors.
• Functional asplenia-induced leukocyte demargination may lead to a predominance of dysfunctional neutrophils, exacerbating infection risk in SCD.