Hematology & immune disorders
Primary immunodeficiency disorders
CR3 deficiency
Author: Shamayel Mohammed, M.D.
Last author update: 1 October 2015
Last staff update: 25 February 2021
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: CR3 deficiency
Table of Contents
Definition / general | Pathophysiology | Clinical features | Diagnosis | Laboratory | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Mohammed S. CR3 deficiency. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphnodesCR3deficiency.html. Accessed December 4th, 2024.
Definition / general
- CR3 deficiency is an autosomal recessive inherited deficiency of the leukocyte beta2 integrin receptor CD11/18 (CR3) causing leukocyte adhesion deficiency syndrome I (LAD I) (Clin Exp Immunol 2000;121:133)
- Migration and adhesion of leukocytes from the bloodstream to site of infection involves multiple steps of the adhesion cascade
- Adhesion molecules are expressed on endothelial cells and leukocytes.
- CD11/CD18 (CR3), also known as the leukocyte beta2 integrin receptor, is one of the main adhesion molecules essential for leukocyte adhesion to endothelial cells and chemotaxis
- Defects in these adhesion molecules as well other adhesion molecules result in recognized clinical syndromes
- Three leukocyte-adhesion deficiency (LAD) syndromes have been delineated (LAD I, LAD II, LAD III) (Blood Cells Mol Dis 2001;27:1000)
- The deficiency / defect leads to impaired phagocytic function
Pathophysiology
- Four distinct complement receptors, CR1, CR2, CR3 and CR4, have been described for the surface bound complement fraction C3 and its cleavage fragments such as iC3b
- Complement and complement receptors are an integral part of the immune defense
- CR3 (CD11b/18) and CR4 (CD11c/18) both bind to iC3b and facilitate adequate adhesion of leucocytes with the vascular endothelium
- Receptors such as CR3 act as ligands for adhesion molecules, and are present on phagocytic cells
- CR3 and CR4 have an important role in host resistance to infection
Clinical features
- Recurrent cutaneous infections and gingivitis
- Delayed separation of the umbilical cord and secondary omphalitis
- Severe recurrent Staphylococcus aureus and gram negative bacterial infections
- Periodontitis and impaired wound healing
- Leukocytosis with lack of pus formation
Diagnosis
- Absence of CD18 and the associated alpha subunit molecules CD11a, CD11b and CD11c on the surface of leukocytes is demonstrated by flow cytometry using CD11 and CD18 monoclonal antibodies
- Sequence analysis can define the exact molecular defect in the beta 2 subunit
Laboratory
- Neutrophilia
Case reports
- 18 month old girl with leukocyte adhesion deficiency (Pediatr Pathol 1992;12:119)
- 5 year old boy (J Dent Child (Chic) 2012;79:105)
- 31 year old man with pyoderma gangrenosum-like lesions (Pediatr Dermatol 2011;28:156)
Treatment
- Symptomatic
- Bone marrow and hematopoietic stem cell transplant
Clinical images
Images hosted on other servers:
Skin lesions
Gingivitis, periodontitis
Microscopic (histologic) description
- Severe lymph node hypoplasia with small, poorly delineated germinal centers
- Lymphoid tissue, including the thymus, is depleted of lymphocytes (Pediatr Pathol 1992;12:119)
- Biopsies of infected tissues demonstrate inflammatory infiltrates completely devoid of neutrophils
Microscopic (histologic) images
Images hosted on other servers:
Clinical and histological profile
IL-17 signature
Skin biopsy
Molecular / cytogenetics description
- Sequence analysis to define the exact molecular defect in the beta 2 subunit (Prenat Diagn 1991;11:193)
Differential diagnosis
- Common variable immunodeficiency
- Neutrophilia can be caused by
- Infections
- Leukemoid reaction in infants
- Acute leukemia
- Less likely other lymphoproliferative disorders
