PMN disorders and deficiencies: Impaired neutrophil function enhances the risk of infections, particularly with bacteria or Candida, dramatically. In addition to transient or iatrogenic-induced reduction of PMN activity (e.g. in the context of severe virus infections, trauma, immunosuppressive or antibiotic therapy), congenital disorders of PMN are described. Of some, the underlying molecular defects are known. The leukocyte adhesion deficiency (LAD) 1 syndrome is caused by a reduced or deficient expression of the adhesion molecule CD11b/CD18 (a.k.a. CR3 or Mac-1). Chronic granulomatous disease (“CGD-syndrome”) is due to an enzyme defect – most frequently of cytochrome b558 (a.k.a. gp91) – within the cascade involved in the generation of oxygen radicals. Although the exact pathogenesis of congenital neutropenia or cyclic neutropenia is not yet known, there is a link to a genetic defect in the elastase gene. Moreover, granule deficiencies are described. Also other functional deficiencies, e.g. of phagocytosis, can occur; the molecular basis of these, however, has not yet been elucidated, in part because only very few patients are affected. Aside from the classical therapeutic approach, prevention and antibiotic therapy, bone marrow transplantation is an option and there are promising trials for gene therapy in patients with CGD
