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[Hereditary polymorphonuclear neutrophil deficiencies]
S Chollet-Martin1, M A Gougerot-Pocidalo
1Service d'hématologie et d'immunologie biologiques et Inserm U479, CHU Bichat-Claude-Bernard, 46, rue Henri-Huchard, 75018 Paris, France.
Abstract:
Rare hereditary deficiencies have been described which affect each functional stage of polymorphonuclear neutrophils. They almost invariably lead to recurrent acute infection. Among the abnormalities involving adhesion and motility, the following can be noted: the Buckley syndrome; and leucocyte type 1 and 2 adhesion deficiencies, respectively caused by a deficiency in membrane expression of beta 2 integrin CD11/CD18, and sialyl lewis X. Granulation system abnormalities include relatively non-symptomatic myeloperoxidase deficiency, specific granulation deficiency or the Chediak-Higashi syndrome with the presence of giant lysosomal granulations. Chronic or familial septic granulomatosis constitutes the main disease described due to the oxidative PMN burst connected with the functional impairment of one of the constituents of NADPH oxidase (with an incidence of one in 5.10(6) to one in 10(6) births) The transmission is X-linked, or autosomal recessive depending on the mutation. The antenatal detection of the X-linked component, gp91 phox, can be made in suspected carrier mothers. In addition to the standard treatment (Bactrim and Itraconazole), bone marrow transplantation may also be carried out, and in future gene therapy may be introduced.
Insights
Rare hereditary neutrophil disorders cause recurrent infections. Deficiencies in adhesion, motility, granulation, or the oxidative burst, like chronic granulomatous disease, are discussed, with treatment options including bone marrow transplantation and potential gene therapy.
Area of Science:
- Immunology
- Hematology
- Genetics
Background:
- Rare hereditary deficiencies affect polymorphonuclear neutrophil (PMN) functions, leading to recurrent infections.
- Abnormalities span adhesion, motility, granulation, and the oxidative burst.
- Examples include Buckley syndrome, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, and chronic granulomatous disease.
Purpose of the Study:
- To review hereditary neutrophil disorders affecting PMN function.
- To highlight key syndromes and their underlying molecular defects.
- To discuss current and future therapeutic strategies.
Main Methods:
- Literature review of hereditary neutrophil disorders.
- Categorization of defects based on affected PMN functional stages.
- Summary of genetic transmission patterns and diagnostic approaches.
Main Results:
- Defects in adhesion/motility involve CD11/CD18 or sialyl Lewis X deficiencies.
- Granulation abnormalities include myeloperoxidase deficiency and Chediak-Higashi syndrome.
- Chronic granulomatous disease, due to NADPH oxidase defects, has an incidence of 1 in 5x10^6 to 1x10^6 births.
Conclusions:
- Hereditary neutrophil disorders present with recurrent infections due to specific PMN functional defects.
- Antenatal detection is possible for X-linked forms (e.g., gp91 phox).
- Treatment involves antimicrobials, bone marrow transplantation, and potential future gene therapy.