Primary disorders of phagocytic function: An overview
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Associate Professor of Pediatrics
- Harvard Medical School
Susceptibility to infection from phagocytic dysfunction ranges from mild, recurrent skin infections to overwhelming, fatal systemic infection. Affected patients are more susceptible to bacterial and fungal infections but have a normal resistance to viral infections. Most are diagnosed in infancy due to the severity of the infection or the unusual presentation of the organism, but some escape diagnosis until adulthood.
This topic review provides a brief overview of the types of defects and typical presentation of primary phagocytic disorders. The major disorders resulting from defects of phagocytic function are also briefly discussed. (Detailed discussions of these disorders are presented separately. See links in respective sections below.)
A detailed discussion of methods used in the evaluation of immune system function is found separately. (See "Laboratory evaluation of the immune system".)
TYPES OF DEFECTS
Phagocytic disorders may be divided into extrinsic and intrinsic defects:
●Extrinsic defects include opsonic abnormalities secondary to deficiencies of antibody and complement factors. Extrinsic factors may lead to neutropenia by suppression of granulocyte production or cause a decrease in the number of circulating neutrophils via leukocyte autoantibodies or isoantibodies directed against neutrophil antigens.
- Dinauer MC. Disorders of neutrophil function: an overview. Methods Mol Biol 2014; 1124:501.
- Bouma G, Ancliff PJ, Thrasher AJ, Burns SO. Recent advances in the understanding of genetic defects of neutrophil number and function. Br J Haematol 2010; 151:312.
- Holland SM. Chronic granulomatous disease. Hematol Oncol Clin North Am 2013; 27:89.
- van de Vijver E, van den Berg TK, Kuijpers TW. Leukocyte adhesion deficiencies. Hematol Oncol Clin North Am 2013; 27:101.
- Kuijpers TW, van de Vijver E, Weterman MA, et al. LAD-1/variant syndrome is caused by mutations in FERMT3. Blood 2009; 113:4740.
- Farmand S, Sundin M. Hyper-IgE syndromes: recent advances in pathogenesis, diagnostics and clinical care. Curr Opin Hematol 2015; 22:12.
- Yang L, Fliegauf M, Grimbacher B. Hyper-IgE syndromes: reviewing PGM3 deficiency. Curr Opin Pediatr 2014; 26:697.
- Roth S, Ruland J. Caspase recruitment domain-containing protein 9 signaling in innate immunity and inflammation. Trends Immunol 2013; 34:243.
- Glocker EO, Hennigs A, Nabavi M, et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med 2009; 361:1727.
- Drewniak A, Gazendam RP, Tool AT, et al. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood 2013; 121:2385.
- Lanternier F, Pathan S, Vincent QB, et al. Deep dermatophytosis and inherited CARD9 deficiency. N Engl J Med 2013; 369:1704.
- Wang X, Wang W, Lin Z, et al. CARD9 mutations linked to subcutaneous phaeohyphomycosis and TH17 cell deficiencies. J Allergy Clin Immunol 2014; 133:905.
- Lanternier F, Barbati E, Meinzer U, et al. Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection. J Infect Dis 2015; 211:1241.
- Pérez de Diego R, Sánchez-Ramón S, López-Collazo E, et al. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity. J Allergy Clin Immunol 2015; 136:1139.
- Hajishengallis G, Chavakis T, Hajishengallis E, Lambris JD. Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis. J Leukoc Biol 2015; 98:539.
- Bustamante J, Boisson-Dupuis S, Abel L, Casanova JL. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity. Semin Immunol 2014; 26:454.
- TYPES OF DEFECTS
- TYPICAL PRESENTATION
- CHRONIC GRANULOMATOUS DISEASE
- LEUKOCYTE ADHESION DEFICIENCIES
- HYPERIMMUNOGLOBULIN E SYNDROMES
- MYELOPEROXIDASE DEFICIENCY
- CHEDIAK-HIGASHI SYNDROME
- NEUTROPHIL-SPECIFIC GRANULE DEFICIENCY
- CARD9 DEFICIENCY
- SHWACHMAN-DIAMOND SYNDROME
- PERIODONTITIS SYNDROMES
- MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE (MSMD)
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS