Table 2.
Neutrophil Disorders and Infection.
| Disease | Defect | PMN Dysfunction | Clinical Outcomes |
|---|---|---|---|
| Neutropenia | Decreased PMN numbers, either congenital (e.g., elastase deficiency) or acquired (most commonly drug-induced such as cancer chemotherapy). | Insufficient PMN numbers to respond to invading pathogens, life-threatening Gram-negative and Gram-positive infections. | Life-threatening infections during periods of neutropenia, susceptibility reduced when neutrophil count recovers. |
| Chronic granulomatous disease (CGD) | Mutations in NADPH oxidase components; reduced or absent ROS formation. | Reduced killing of certain pathogens e.g., Staphylococcus aureus, Aspergillus fumigatus, Gram- negative bacilli. | Life-threatening infections with Staphylococcus and Apergillus; aberrant healing (granulomas). |
| Hyper IgE Syndrome (formerly Job’s Syndrome) | Mutations in STAT3 (signal transducer and activator of transcription 3) or DOCK 8 (Dedicator of cytokinesis 8) or TYK2 leading to impaired T cell function and diminished neutrophil chemotaxis | Reduced killing of certain pathogens e.g., Staphylococcus aureus, Aspergillus fumigatus. | Staphylococcal and fungal skin infections, pulmonary and joint infections, ‘cold’ abscess formation (reduced cytokine release). |
| Myeloperoxidase deficiency | Decreased or lack of MPO/HOCl system required to generate the full range of ROS. | Increased chronic conditions mediated by adaptive immunity, decreased NET killing of microbes. | Susceptibility to chronic infections caused by Candida albicans, S. aureus. |
| SGD (Specific Granule Deficiency) | Absence of specific granules, bilobed neutrophils nuclei. Altered content of other granule populations. | Impaired chemotaxis, aberrant granule organisation, reduced respiratory burst, and deficient bactericidal activity (mainly to S. aureus). | Staphylococcal skin infections, aberrant skin lesion healing. |
| Chediak Higashi Syndrome | Mutations in lysosomal trafficking regulator (LYST) leading to failure of lysosomal trafficking in neutrophils and other cells | Giant granules, impaired phagocytosis and phagosomal maturation, oxidative burst and degranulation | Albinism, neurological defects, coagulopathy, recurrent skin (staphylococcal) infections and respiratory infection |