WordNet

stated explicitly or in detail; "needed a specific amount"
a medicine that has a mitigating effect on a specific disease; "quinine is a specific for malaria"
(sometimes followed by `to'
being or affecting a disease produced by a particular microorganism or condition; used also of stains or dyes used in making microscope slides; "quinine is highly specific for malaria"; "a specific remedy"; "a specific stain is one having a specific affinity for particular structural elements"
relating to or distinguishing or constituting a taxonomic species; "specific characters"
a tiny grain

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《名詞の前にのみ用いて》『特定の』,一定の・『明確な』,明白な・(そのものに)『特有の』,独特の《+『to』+『名』》・〈C〉(…の)特効薬《+『for』+『名』》・《複数形で》明細,細部(details)
〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥
小粒,微粒

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/17 22:31:59」(JST)

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Neutrophil-specific granule deficiency^[1] (SGD, previously known as lactoferrin deficiency) is a rare congenital immunodeficiency characterized by an increased risk for pyogenic infections due to defective production of specific granules and gelatinase granules in patient neutrophils.

Symptoms

Atypical infections are the key clinical manifestation of SGD.^[1] Within the first few years of life, patients will experience repeated pyogenic infections by species such as Staphylococcus aureus, Pseudomonas aeruginosa or other Enterobacteriaceae, and Candida albicans. Cutaneous ulcers or abscesses and pneumonia and chronic lung disease are common. Patients may also develop sepsis, mastoiditis, otitis media, and lymphadenopathy. Infants may present with vomiting, diarrhea, and failure to thrive.^[2]

Diagnosis can be made based upon CEBPE gene mutation or a pathognomonic finding of a blood smear showing lack of specific granules. Neutrophils and eosinophils will contain hyposegmented nuclei (a pseudo-Pelger–Huet anomaly).

Genetics

A majority of patients with SGD have been found to have mutations in the CEBPE (CCAAT/enhancer-binding protein epsilon) gene, a transcription factor primarily active in myeloid cells.^[3] Almost all patients have been found to be homozygous for the mutation, suggesting the disease is autosomal recessive. One patient, heterozygous for the mutation, was found to be deficient in GFI1, a related gene.^[4]

Pathophysiology

The defect in CEBPE appears to block the ability of neutrophils to mature past the promyelocyte stage in bone marrow.^[3] Since specific (secondary) and gelatinase (tertiary) granules are only produced past the promyelocyte stage of development, these are deficient in SGD. Lactoferrin is the major enzyme found in specific granules, and will be largely absent in the granulocytes of these patients, along with defensins (despite these also being found in azurophilic (primary) granules).^[5] The other major components of azurophilic granules, such as lysozyme, cathepsin, and elastase will be normal, however a lack of defensins and lactoferrin drastically weakens the neutrophil innate ability to fight infection. Neutrophils will also display abnormal chemotaxis, such as a decreased response to fMLP, due to a lack of chemotactic receptors typically found in the specific granules.^[6]

Treatment

Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases.^[2] Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood.

Epidemiology

Estimation of the frequency of SGD is difficult, as it is an extremely rare disease with few cases reported in literature. The condition was first reported in 1980, and since only a handful more cases have been published.

External links

UptoDate Article

References

^ ^a ^b Breton-Gorius J, Mason DY, Buriot D, Vilde JL, Griscelli C (1980). "Lactoferrin deficiency as a consequence of a lack of specific granules in neutrophils from a patient with recurrent infections. Detection by immunoperoxidase staining for lactoferrin and cytochemical electron microscopy". Am. J. Pathol. 99 (2): 413–28. PMC 1903492. PMID 6155073.
^ ^a ^b Wynn RF, Sood M, Theilgaard-Mönch K, Jones CJ, Gombart AF, Gharib M, Koeffler HP, Borregaard N, Arkwright PD (2006). "Intractable diarrhoea of infancy caused by neutrophil specific granule deficiency and cured by stem cell transplantation". Gut 55 (2): 292–3. doi:10.1136/gut.2005.081927. PMC 1856503. PMID 16407388.
^ ^a ^b Lekstrom-Himes JA, Dorman SE, Kopar P, Holland SM, Gallin JI (1999). "Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein epsilon". J. Exp. Med. 189 (11): 1847–52. PMC 2193089. PMID 10359588.
^ Khanna-Gupta A, Sun H, Zibello T, Lee HM, Dahl R, Boxer LA, Berliner N (2007). "Growth factor independence-1 (Gfi-1) plays a role in mediating specific granule deficiency (SGD) in a patient lacking a gene-inactivating mutation in the C/EBPepsilon gene". Blood 109 (10): 4181–90. doi:10.1182/blood-2005-05-022004. PMC 1885490. PMID 17244686.
^ Ganz T, Metcalf JA, Gallin JI, Boxer LA, Lehrer RI (1988). "Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and "specific" granule deficiency". J. Clin. Invest. 82 (2): 552–6. doi:10.1172/JCI113631. PMC 303547. PMID 2841356.
^ Gallin JI, Fletcher MP, Seligmann BE, Hoffstein S, Cehrs K, Mounessa N (1982). "Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response". Blood 59 (6): 1317–29. PMID 7044447.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 好中球二次顆粒欠損症 neutrophil specific granule deficiency
2. 貧食細胞機能の原発性疾患：概要 primary disorders of phagocytic function an overview
3. 免疫系の臨床検査評価 laboratory evaluation of the immune system
4. 感染症を繰り返す成人に対するアプローチ approach to the adult with recurrent infections

English Journal

A Novel In-Frame Deletion in the Leucine Zipper Domain of C/EBPε Leads to Neutrophil-Specific Granule Deficiency.

Wada T1, Akagi T2, Muraoka M3, Toma T3, Kaji K4, Agematsu K5, Koeffler HP6, Yokota T2, Yachie A3.
Journal of immunology (Baltimore, Md. : 1950).J Immunol.2015 Jul 1;195(1):80-6. doi: 10.4049/jimmunol.1402222. Epub 2015 May 27.
Neutrophil-specific granule deficiency (SGD) is a rare autosomal recessive primary immunodeficiency characterized by neutrophil dysfunction, bilobed neutrophil nuclei and lack of neutrophil-specific granules. Defects in a myeloid-specific transcription factor, CCAAT/enhancer binding protein-ε (C/EB
PMID 26019275

The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study.

Ye Y1, Carlsson G2, Karlsson-Sjöberg JM3, Borregaard N4, Modéer TU5, Andersson ML3, Pütsep KL3.
Scientific reports.Sci Rep.2015 Jun 29;5:11685. doi: 10.1038/srep11685.
The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels
PMID 26119962

Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration.

Sumagin R1, Parkos CA1.
Tissue barriers.Tissue Barriers.2015 Apr 3;3(1-2):e969100. doi: 10.4161/21688362.2014.969100. eCollection 2015.
Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from
PMID 25838976

Japanese Journal

Neutrophil specific granule deficiency and mutations in the gene encoding transcription factor C/EBP (ε)

GOMBART AF
Curr Opin Hematol 9, 36-42, 2002
NAID 30018769275

Neutrophil-specific granule deficiency : homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein-ε

GOMBART AF
Blood 97, 2561-2567, 2001
NAID 30022493109

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リンク元	「特殊顆粒欠損症」
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関連記事	「deficiency」「specific」「granule」