Phagocyte Deficiencies

Phagocyte Deficiencies

Phagocyte deficiencies include (a) chronic granulomatous disease, (b) Chediak–Higashi syndrome, (c) Job’s syndrome, (d) leukocyte adhesion deficiency, (e) myeloperoxidase defi-ciency, and ( f ) cyclic neutropenia.

◗ Chronic granulomatous disease

Chronic granulomatous disease (CGD) is a disorder that is inherited as an X-linked trait in two-thirds of the cases and as an autosomal recessive trait in the remaining one-third. Clinical manifestations are usually apparent before the end of the 2nd year of life. This is a condition associated with defi-ciency of an enzyme NADPH oxidase. This enzyme deficiency causes neutrophils and monocytes to have decreased consump-tion of oxygen and diminished glucose utilization by the hex-ose monophosphate shunt. Although neutrophils phagocytose microorganisms, they do not form superoxide and other oxy-gen intermediates that usually constitute the respiratory burst. All of these lead to decreased intracellular killing of bacteria and fungi. Thus, these individuals have an increased suscepti-bility to infection with microorganisms that normally are of relatively low virulence. These include Aspergillus, Serratia marc-escens, and Staphylococcus epidermidis.

Patients with CGD may have hepatosplenomegaly, pneu-monia, osteomyelitis, abscesses, and draining lymph nodes.

The quantitative nitroblue tetrazolium (NBT) test and the quantitative killing curve are both employed to confirm the diagnosis of CGD. Therapy includes interferon gamma, antibiotics, and surgical drainage of abscesses.

◗ Chediak–Higashi syndrome

It is a childhood disorder with an autosomal recessive mode of inheritance. The condition is identified by the presence of large lysozomal granules in leukocytes that are very stable and undergo slow degranulation. The large cytoplasmic granular inclusions that appear in white blood cells may also be observed in blood platelets and can be seen by regular light microscopy in peripheral blood smears. The condition is characterized by a defective neutrophil chemotaxis and an altered ability of the cells to kill ingested microorganisms. The majority of affected individuals die during childhood, although occasional cases may live longer.

There is no effective therapy other than the administration of antibiotics for treatment of the infecting microorganisms. High doses of ascorbic acid have been shown to restore normal chemotaxis, bactericidal activity, and degranulation.

◗ Job’s syndrome

Job’s syndrome is caused by failure of helper T cells to produce gamma interferon, which in turn reduces the ability of mac-rophages to kill bacteria. This results in an increased produc-tion of Th-2 and consequently an increased production of IgE. All these in turn cause more production of histamine that prevents certain components of inflammatory reaction and also inhibits chemotaxis. Therefore, the patient with this syndrome suffers repeatedly from staphylococcal abscesses as well as eczema with a high level of IgE.

◗ Leukocyte adhesion deficiency

It is an autosomal recessive disease caused by mutation in the gene encoding the B chain of an integrin that mediates adhesion of leukocytes to microbes. This causes poor adhe-sion of neutrophils to endothelial surfaces; hence phagocytosis of bacteria is inadequate.

◗ Cyclic neutropenia

It is an autosomal dominant disease in which there is a mutation in the gene encoding neutrophil esterase, an enzyme produced by neutrophils. The disease is characterized by a very low neutrophil count, less than 200/mL for 3–6 days of a 21-day cycle. The patients are susceptible to life-threatening bacterial infections during these 3–6 days of low neutrophil count but not when neutrophil counts are normal.

◗ Myeloperoxidase deficiency

It is a disease associated with deficiency of an enzyme myeloper-oxidase, which is essential for the production of hypochlorite, a microbicidal agent. The deficiency of this enzyme is fre-quently seen but has little clinical importance. This is because other intracellular killing mechanisms of leukocytes are intact.