| Degranulation abnormalities | | |
| Chédiak-Higashi syndrome | Autosomal recessive; disordered coalescence of lysosomal granules; responsible gene is CHSI/LYST, which encodes a protein hypothesized to regulate granule fusion | Decreased neutrophil chemotaxis; degranulation and bactericidal activity; platelet storage pool defect; impaired NK function, failure to disperse melanosomes | Neutropenia; recurrent pyogenic infections, propensity to develop marked hepatosplenomegaly as a manifestation of the hemophagocytic syndrome |
| Specific granule deficiency | Autosomal recessive; functional loss of myeloid transcription factor arising from a mutation or arising from reduced expression of Gfi-1 or C/eBpε, which regulates specific granule formation | Impaired chemotaxis and bactericidal activity; bilobed nuclei in neutrophils; defensins, gelatinase, collagenase, vitamin B12-binding protein, and lactoferrin | Recurrent deep-seated abscesses |
| Adhesion abnormalities |
| Leukocyte adhesion deficiency I | Autosomal recessive; absence of CD11/CD18 surface adhesive glycoproteins (β2 integrins) on leukocyte membranes most commonly arising from failure to express CD18 mRNA | Decreased binding of C3bi to neutrophils and impaired adhesion to ICAM-1 and ICAM-2 | Neutrophilia; recurrent bacterial infection associated with a lack of pus formation |
| Leukocyte adhesion deficiency II | Autosomal recessive; loss of fucosylation of ligands for selectins and other glycol conjugates arising from mutations of the GDP-fucose transporter | Decreased adhesion to activated endothelium expressing ELAM | Neutrophilia; recurrent bacterial infection without pus |
| Leukocyte adhesion deficiency III (LAD-I variant syndrome) | Autosomal recessive; impaired integrin function arising from mutations of FERMT3, which encodes kindlin-3 in hematopoietic cells; kindlin-3 binds to β-integrin and thereby transmits integrin activation | Impaired neutrophil adhesion and platelet activation | Recurrent infections, neutropenia, bleeding tendency |
| Disorders of cell motility |
| Enhanced motile responses; FMF | Autosomal recessive gene responsible for FMF on chromosome 16, which encodes for a protein called “pyrin”; pyrin regulates caspase-1 and thereby IL-1β secretion; mutated pyrin may lead to heightened sensitivity to endotoxin, excessive IL-1β production, and impaired monocyte apoptosis | Excessive accumulation of neutrophils at inflamed sites, which may be the result of excessive IL-1β production | Recurrent fever, peritonitis, pleuritis, arthritis, and amyloidosis |
| Depressed motile responses |
| Defects in the generation of chemotactic signals | IgG deficiencies; C3 and properdin deficiency can arise from genetic or acquired abnormalities; mannose-binding protein deficiency predominantly in neonates | Deficiency of serum chemotaxis and opsonic activities | Recurrent pyogenic infections |
| Intrinsic defects of the neu-trophil (eg, leukocyte adhesion deficiency, hédiak-Higashi syndrome, specific granule deficiency, neutrophil actin dysfunction, neonatal neutrophils); direct inhibition of neutrophil mobility (eg, drugs) | In the neonatal neutrophil there is diminished ability to express β2 integrins and there is a qualitative impairment in β2-integrin function; ethanol, glucocorticoids, cyclic AMP | Diminished chemotaxis; impaired locomotion and ingestion; impaired adherence | Propensity to develop ... |