WordNet

a fibrous band of scar tissue that binds together normally separate anatomical structures
abnormal union of bodily tissues; most common in the abdomen
a pattern of symptoms indicative of some disease
a complex of concurrent things; "every word has a syndrome of meanings"
blood cells that engulf and digest bacteria and fungi; an important part of the bodys defense system (同)leucocyte, white_blood_cell, white_cell, white blood corpuscle, white_corpuscle, WBC

PrepTutorEJDIC

〈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
粘着,付着
(疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/01 01:50:51」(JST)

wiki en

Leukocyte adhesion deficiency (LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections.^[1] LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a Glanzmann thrombasthenia-like bleeding tendency.^[2]^[3]

Characteristics

LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing. The adhesion defects result in poor leukocyte chemotaxis, particularly neutrophil, inability to form pus and neutrophilia.^[3]

Individuals with LAD suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, and peritonitis are common and often life-threatening due to the infant's inability to properly destroy the invading pathogens. These individuals do not form abscesses because granulocytes cannot migrate to the sites of infection.

Cause and genetics

Leukocyte-adhesion deficiency has an autosomal recessive pattern of inheritance.

Types include:

Type	OMIM	Gene
LAD1	116920	ITGB2
LAD2 or CDG2C	266265	SLC35C1
LAD3	612840	FERMT3

The most common type is LAD1.

The inherited molecular defect in patients with LAD1 is a deficiency of the β-2 integrin subunit,^[4] also called CD18, which is encoded by the ITGB2 gene (found in chromosome 21). This subunit is involved in the formation of the β-2 integrins (LFA-1, Integrin alphaXbeta2, and Mac-1/CR3) by the dimerization with different CD11 subunits. Mutations in ITGB2 gene lead to absent, reduced or aberrant CD18 protein expression. The final results in the no expression in the leukocyte membrane of the β-2 integrins. The main function of these proteins in allowing neutrophils to make their way out of the blood stream to the infected tissues by adhering to different ligands expressed by the endothelium (e.g. ICAM-1). In LAD-I patients, neutrophils can not extravasate and fight against bacteria in the tissues. The bacteria can then proliferate, leading to symptomatic infection. The infection can spread unimpeded and cause serious injury to important tissue.

Diagnosis

Typically, diagnosis is made after several preliminary tests of immune function are made, including basic evaluation of the humoral immune system and the cell-mediated immune system. A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels. In the case of LAD-I, specific diagnosis is done by flow cytometry. This technique will reveal absent or reduced CD18 expression in the leukocyte membrane. Recently, prenatal diagnosis systems has been established, allowing an early detection of the disease. LAD-II diagnosis includes the study of different glycosilated forms of the transferrin protein. In LAD-III, as platelet function is also affected, this could be used to differentiate it from the other types.

Treatment

Although patients can receive intensive antibiotherapy and even granulocyte transfusions from healthy donors, the only current curative therapy is the hematopoietic stem cell transplant.^[5] However, progress has been made in gene therapy, an active area of research. Both foamyviral and lentiviral vectors expressing the human ITGB2 gene under the control of different promoters have been developed and have been tested so far in preclinical LAD-I models (such as CD18-deficient mice and canine leukocyte adhesion deficiency-affected dogs).

Epidemiology

LAD is a rare disease, with an estimated prevalence of one in 100,000 births, with no described racial or ethnic predilection. The most common type is LAD1.

External links

Immune Deficiency Foundation
Leukocyte Adhesion Deficiency Web Site

References

^ "Leukocyte Adhesion Deficiency: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.
^ Robert P, Canault M, Farnarier C, Nurden A, Grosdidier C, Barlogis V, … Alessi MC (2011). "A novel leukocyte adhesion deficiency III variant: kindlin-3 deficiency results in integrin- and nonintegrin-related defects in different steps of leukocyte adhesion". Journal of Immunology 186 (9): 5273–83. doi:10.4049/jimmunol.1003141. PMID 21441448.
^ ^a ^b Abbas AK, Lichtman AH, Pillai S (2012). Cellular and molecular immunology (7th ed.). Philadelphia: Elsevier/Saunders. ISBN 1437715281.
^ Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA (1987). "Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency". Cell 50 (2): 193–202. doi:10.1016/0092-8674(87)90215-7. PMID 3594570.
^ van Vliet DN, Brandsma AE, Hartwig NG (2004). "Leukocyte-adhesion deficiency - a rare disorder of inflammation". Ned Tijdschr Geneeskd. 145 (50): 2496–2500. PMID 15638198.

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. 白血球粘着不全症 leukocyte adhesion deficiency
2. 貧食細胞機能の原発性疾患：概要 primary disorders of phagocytic function an overview
3. 炎症の病因における白血球内皮細胞接着 leukocyte endothelial adhesion in the pathogenesis of inflammation
4. 好中球増多症の原因 causes of neutrophilia
5. 好中球減少症および好中球機能不全の検査での評価 laboratory evaluation of neutropenia and neutrophil dysfunction

English Journal

Hematopoietic Stem Cell Transplant for Primary Immunodeficiency Diseases: A Single-Center Experience.

Patiroglu T1, Akar HH, Unal E, Ozdemir MA, Karakukcu M.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation.Exp Clin Transplant.2016 Mar 21. doi: 10.6002/ect.2015.0233. [Epub ahead of print]
OBJECTIVES: The only curative treatment for many patients with primary immunodeficiency disease is hematopoietic stem cell transplant. In this study, we report the transplant outcomes of patients with primary immunodeficiency diseases.MATERIALS AND METHODS: Herein, we present the transplant outcomes
PMID 27001505

The kindlin family: functions, signaling properties and implications for human disease.

Rognoni E1, Ruppert R1, Fässler R2.
Journal of cell science.J Cell Sci.2016 Jan 1;129(1):17-27. doi: 10.1242/jcs.161190.
The kindlin (or fermitin) family of proteins comprises three members (kindlin-1,-2 and -3) of evolutionarily conserved focal adhesion (FA) proteins, whose best-known task is to increase integrin affinity for a ligand (also referred as integrin activation) through binding of β-integrin tails. The co
PMID 26729028

Budd-Chiari Syndrome in a Child With Leukocyte Adhesion Deficiency-A Rare Association.

Bhattad S1, Rawat A1, Gupta A1, Suri D1, Saikia B2, Minz RW2, Sodhi KS3, Singh S1.
Pediatric blood & cancer.Pediatr Blood Cancer.2015 Dec;62(12):2244. doi: 10.1002/pbc.25630. Epub 2015 Jul 7.
PMID 26154877

Japanese Journal

Successful human leukocyte antigen one antigen-mismatched related bone marrow transplantation in a 6-yaer-old boy with leukocyte adhesion deficiency syndrome

Pediatrics international : official journal of the Japan Pediatric Society 43(3), 306-309, 2001-06-01
NAID 10010092508