Disorders of Neutrophil Function
Disease Genetics Pathologic Findings Clinical Findings
Chronic Granulomatous Disease (CGD) Mutations in genes coding for phox proteins in the NADPH oxidative killing pathway; X-linked mutation in 60% of cases and more severe than the autosomal recessive forms. Normal numbers of neutrophils but decreased killing of microorganisms ingested by phagocytes, mainly granulocytes; defect in flow cytometry respiratory burst assay Beginning in childhood lymphadenitis, liver abscesses, osteomyelitis, pneumonia, or skin infections with granulomatous inflammation from recurrent infections. Causative agents are catalase positive bacteria including Staphylococcus aureus, Serratia marcescens, Salmonella species, and Burkholderia cepacia, along with fungal Aspergillus. Autoimmunity possible.
Chediak-Higashi Syndrome (CHS) Mutations in the CHS1/LYST gene encoding a protein that regulates lysosome-related organelle size and movement Affected cells have enlarged cytoplasmic vesicles including lysosomes, melanosomes (with variable albinism), platelet dense granules (with bleeding), and cytolytic granules; abnormal fusion of lysosomes forms giant granules in peripheral blood granulocytes Recurrent severe bacterial infections and progressive neurologic problems including weakness, ataxia, sensory deficits, and neurodegeneration. Risk for aggressive lymphoproliferative disorder with NK and cytotoxic T cells infiltrating major organs
Leukocyte Adhesion Deficiency (type 1) Autosomal recessive mutations in the CD18 gene, encoding the common beta chain of cellular integrins that aid in binding of leukocytes to endothelium prior to diapedesis Marked peripheral blood neutrophilia but absence of suppurative inflammation and poor wound healing in areas of tissue necrosis and ulceration caused by Staphylococcus aureus and gram-negative enteric bacteria, sometimes fungi Recurrent subcutaneous and mucosal infections, septicemia, poor wound healing