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Pediatric Complement Receptor Deficiency Follow-up

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Feb 11, 2013
 

Further Outpatient Care

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  • Outpatient intravenous antibiotics, usually through a percutaneous line or central line, can be administered to treat infections.
  • Surgical treatment has been performed when necessary, and the organism has been identified.
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Further Inpatient Care

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  • Inpatient care is required to treat infections in patients with leukocyte adhesion deficiency (LAD), which is caused by complement receptor deficiency.
  • Patients with infections may need surgical drainage, debridement, and intravenous antibiotics.
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Deterrence/Prevention

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  • Education of the parents and patient for early recognition and need for early treatment of infections is essential.
  • Good oral hygiene is important to manage the oral infections (eg, gingivitis, periodontitis).
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Prognosis

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  • The prognosis of patients with the LAD type 1 severe phenotype is poor; these patients require immune reconstitution.
  • Patients with mild and moderate phenotypes of LAD type 1 have infections of decreased severity.
  • CD18 expression of 10% seems to confer protection against invasive life-threatening infections.[9]
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Contributor Information and Disclosures
Author

Alan P Knutsen, MD Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director Jeffrey Modell Diagnostic & Research Center for Primary Immuodeficiences (CGCMC), Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center

Alan P Knutsen, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Acknowledgements

John Wilson Georgitis, MD Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

References
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Protein defects.
Table 1. Complement Receptors
ReceptorCluster DesignationLigandCell DistributionActivity
CR1CD35C3b/C4bRBC, polymorphonuclear cell, macrophage, B cell, follicular dendritic cellImmune adherence, phagocytosis
CR2CD21C3dg/C3dB cell, follicular dendritic cellCo-receptor for B-cell signaling
CR3CD11b/CD18C3bi, ICAMMyeloidPhagocytosis, immune adherence
CR4CD11c/CD18C3bi, ICAMMyeloidPhagocytosis, immune adherence
C1qRPNoneC1q, MBL, surfactantPolymorphonuclear cell, macrophagePromotes phagocytosis
C3aRNoneC3a, C4aPolymorphonuclear cell, macrophage, epithelial cell, smooth-muscle cellAnaphylatoxin
C4aRNoneC4aPolymorphonuclear cell, macrophage, epithelial cell, smooth-muscle cellAnaphylatoxin
C5aRCD88C5aPolymorphonuclear cell, macrophage, epithelial cell, smooth-muscle cellAnaphylatoxin
ICAM = intercellular adhesion molecule, MBL = mannose-binding lectin
Table 2. Leukocyte Adhesion Defects
DiseaseInheritanceGenetic DefectProtein DefectAffected CellsAffected FunctionManifestations
LAD type 1Autosomal recessiveINTGB2CD18Polymorphonuclear cell, macrophage, lymphocytes, NK cellsTight adherence, chemotaxis, endocytosis, T-cell/NK-cell cytotoxicityDelayed cord separation, skin ulcers, periodontitis, leukocytosis, poor pus formation
LAD type 2Autosomal recessiveFUCT1 encoding for GDP-fucose transporterFucosylated proteins, sialyl-Lewis X (sLeX, CD15s)Polymorphonuclear cell, macrophageRolling, chemotaxis, tetheringSame as LAD type 1 plus hh-blood group, mental retardation
LAD type 3Autosomal recessiveKindlin 3 (FERMT3), involved in activation of integrinKindlin 3Polymorphonuclear cell, macrophage, lymphocytes, NK cellsTight adherenceSame as LAD type 1 plus bleeding tendency
Rac 2 deficiencyPossibly autosomal dominantRAC2Rac2, involved in regulation of actin cytoskeletonPolymorphonuclear cell, decreased TRECsChemotaxis, O2- productionRecurrent infections, poor wound healing, leukocytosis, poor pus formation
E-selectinPossibly autosomal recessiveUnknownE-selectinEndothelial cellsRolling, tetheringRecurrent infections, poor pus formation, mild neutropenia
NK = Natural killer, TRECs = T-cell receptor excision circles
Table 3. Adhesion Molecules
MoleculeCD NumberDistributionLigandFunction
Integrins
LFA-1CD11a/CD18All leukocytesICAM-1, 2, 3Adhesion, migration
CR3CD11b/CD18Polymorphonuclear cell, macrophage, NK cells, eosinophilsICAM-1,2; C3biAdhesion, migration
CR4CD11c/CD18All leukocytesC3bi, ICAM-1, CD23, fibrinogenAdhesion
Alpha4-beta7NoneLymphocytes, NK cells, eosinophilsMadCAM-1, VCAM-1, fibronectinAdhesion, migration, rolling
VLA-4CD49d/CD29Lymphocytes, NK cells, eosinophils, basophilsVCAM-1, fibronectinAdhesion, migration, rolling
Selectins
ECD62EEndothelial cells, plateletsSialylated, fucosylated molecules (sLeX, CD15s) expressed on PSGL-1 and ESL-1Rolling
PCD62PEndothelial cells, plateletsSialylated, fucosylated molecules (sLeX) expressed on PSGL-1No data
LCD62LLeukocytesSialylated, fucosylated molecules (often sulfated) expressed on CD34, MadCAM-1 and other glycoproteins-1Rolling
MadCAM = Mucosal addressin cell adhesion molecule; VCAM = Vascular cell adhesion molecule; VLA = Very late activation antigen
Table 4. Subtypes of Leukocyte Adhesion Deficiency Type 1
SubtypemRNA levelCD18 ExpressionClinical Presentation
1NoneNoneSevere
2LowTraceModerate
3Reference rangeTrace, small protein precursorModerate
4Reference rangeLarge protein precursorSevere
5Reference rangeNormal protein precursorModerate
mRNA = messenger RNA.
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