Leukocyte adhesion deficiency-1: Difference between revisions
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'''Leukocyte adhesion deficiency-1''' (LAD1) is a rare autosomal recessive disorder attributed in humans to mutations in the ITGB2 gene. This gene encodes [[CD18|CD18 (integrin beta-2)]], a 95 kDa subunit common to several heterodimeric protein complexes expressed as neutrophil surface receptors.<ref>Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:550–564.</ref> LAD1 has been observed in several hundred children and carries a high mortality rate. The primary symptoms of the disorder are severe and recurrent bacterial or fungal infections of soft tissues; these infections are frequently obvious at birth and may spread systemically. Other findings include delayed separation of the umbilical cord, periodontal disease, and impaired wound healing.<ref>Etzioni |
'''Leukocyte adhesion deficiency-1''' (LAD1) is a rare [[Recessive#Autosomal recessive gene|autosomal recessive]] disorder attributed in humans to mutations in the ITGB2 gene. This gene encodes [[CD18|CD18 (integrin beta-2)]], a 95 kDa subunit common to several heterodimeric protein complexes expressed as neutrophil surface receptors.<ref>Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:550–564.</ref> LAD1 has been observed in several hundred children and carries a high mortality rate. The primary symptoms of the disorder are severe and recurrent bacterial or fungal infections of soft tissues; these infections are frequently obvious at birth and may spread systemically. Other findings include delayed separation of the umbilical cord, periodontal disease, and impaired wound healing.<ref>{{cite journal |
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|year=2010 |
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|title=Defects in the leukocyte adhesion cascade |
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|journal=Clinic Rev Allerg Immunol |
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|volume=38 |
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|issue=1 |
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|pages=54–60 |
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|publisher=Springer |
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|doi=10.1007/s12016-009-8132-3 |
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|url=http://www.springerlink.com/content/bk5r3m2817280514/ |
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The protein complexes involved include [[LFA-1]] on B, T, and [[NK]] lymphocytes; complement receptor type 3 (CR3) on [[neutrophils]], [[monocytes]], [[macrophages]], [[eosinophils]], and NK cells; and p150,95 (another complement receptor). The alpha (α) chains of these three molecules are not expressed because of the abnormal beta (β) chain. Humans affected with this disorder have histories of delayed separation of the [[umbilical cord]], [[omphalitis]], [[gingivitis]], recurrent skin infections, repeated otitis media, [[pneumonia]], [[septicemia]], [[ileocolitis]], [[peritonitis]], perianal abscesses, and impaired wound healing.<ref>Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:550–564.</ref> |
The protein complexes involved include [[LFA-1]] on B, T, and [[NK]] lymphocytes; complement receptor type 3 (CR3) on [[neutrophils]], [[monocytes]], [[macrophages]], [[eosinophils]], and NK cells; and p150,95 (another complement receptor). The alpha (α) chains of these three molecules are not expressed because of the abnormal beta (β) chain. Humans affected with this disorder have histories of delayed separation of the [[umbilical cord]], [[omphalitis]], [[gingivitis]], recurrent skin infections, repeated otitis media, [[pneumonia]], [[septicemia]], [[ileocolitis]], [[peritonitis]], perianal abscesses, and impaired wound healing.<ref>Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:550–564.</ref> |
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Leukocyte adhesion deficiency-1 (LAD1) is a rare autosomal recessive disorder attributed in humans to mutations in the ITGB2 gene. This gene encodes CD18 (integrin beta-2), a 95 kDa subunit common to several heterodimeric protein complexes expressed as neutrophil surface receptors.[1] LAD1 has been observed in several hundred children and carries a high mortality rate. The primary symptoms of the disorder are severe and recurrent bacterial or fungal infections of soft tissues; these infections are frequently obvious at birth and may spread systemically. Other findings include delayed separation of the umbilical cord, periodontal disease, and impaired wound healing.[2]
The protein complexes involved include LFA-1 on B, T, and NK lymphocytes; complement receptor type 3 (CR3) on neutrophils, monocytes, macrophages, eosinophils, and NK cells; and p150,95 (another complement receptor). The alpha (α) chains of these three molecules are not expressed because of the abnormal beta (β) chain. Humans affected with this disorder have histories of delayed separation of the umbilical cord, omphalitis, gingivitis, recurrent skin infections, repeated otitis media, pneumonia, septicemia, ileocolitis, peritonitis, perianal abscesses, and impaired wound healing.[3]
Life-threatening bacterial and fungal infections account for the high mortality. Affected people do not have increased susceptibility to viral infections or malignancy. Blood neutrophil counts are usually elevated, even when no infection is present, because of an inability of the cells to adhere to vascular endothelium and migrate out of the intravascular compartment. All cytotoxic lymphocyte functions are impaired because of a lack of the adhesion protein LFA-1. Deficiency of LFA-1 also interferes with immune cell interaction and immune recognition. CR3 binds fixed iC3b fragments of C3 and β-glucans; its absence causes abnormal phagocytic cell adherence and chemotaxis and a reduced respiratory burst with phagocytosis. Flow cytometry with monoclonal antibodies to CD18 or to CD11a, b, or c is used to screen for deficiencies of these glycoproteins. Because the CD18 gene has been cloned and sequenced, this disorder is a potential candidate for gene therapy.[4]
References
- ^ Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:550–564.
- ^ Etzioni, A. (2010). "Defects in the leukocyte adhesion cascade". Clinic Rev Allerg Immunol. 38 (1). Springer: 54–60. doi:10.1007/s12016-009-8132-3.
- ^ Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:550–564.
- ^ Candotti F, Fischer A. Gene therapy. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:688–705.
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