eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Complement Receptor Deficiency: Differential Diagnoses & Workup

Author: Alan P Knutsen, MD, Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center
Contributor Information and Disclosures

Updated: May 20, 2009

Differential Diagnoses

Severe Combined Immunodeficiency

Other Problems to Be Considered

The types of infections and infectious microorganisms that occur in leukocyte adhesion deficiency (LAD) type 1 resemble those that occur in patients with neutropenia. Other defects of neutrophils, such as chronic granulomatous disease (CGD) and hyperimmunoglobulin E (HIE) produce similar susceptibility to infections. However, in both CGD and HIE, lymphadenopathy and splenomegaly occur as well as neutrophil inflammatory response to infections.

Workup

Laboratory Studies

  • Extreme neutrophilia (>15,000/mcL) is a constant feature of leukocyte adhesion deficiency (LAD) type 1, type 2, type 3, and Rac2 deficiency because of inability of neutrophil margination.
    • The WBC count is 15-161 X 103/µL (15,000-161,000/mcL) with 50-90% neutrophils.
    • Neutrophilia is present in the absence of infections and increases with infections.
    • In E-selectin deficiency, mild neutropenia is present but increases with infections.
  • The diagnosis of LAD type 1 is confirmed by an absence of CD11a,b,c/CD18 on neutrophils, macrophages, and lymphocytes on flow cytometry.
    • In addition, neutrophil function is impaired, with abnormal adherence, chemotaxis phagocytosis, and deficient respiratory burst.
    • Numbers of T and B cells and their function are normal.
    • However, natural killer (NK)-cell and T-cell cytotoxicity is depressed.
    • Responses on mixed lymphocyte culture (MLC) may be markedly decreased.
    • CD15s expression is normal in LAD type 1.
  • In LAD type 2, CD15s (sLeX) expression is absent on neutrophils. CD11/CD18 expression is normal.
    • Neutrophil rolling is decreased but adhesion is normal.
    • Numbers and function of T and B cells are decreased.
    • Erythrocyte H antigens are absent, leading to expression of the Bombay (hh) phenotype. As a result, anti-H antibodies are present.
  • In examination of infections in children with LAD type 1, signs of inflammation, eg, erythema, pus formation, are decreased to absent.
    • Necrotic cutaneous, mucous membrane, and periodontal infections are the hallmark of LAD type 1.
    • In deep-seated infections, such as in the lungs and abdomen, the same process occurs.
    • Inflammatory infiltrations are decreased.
    • Therefore, findings on chest or abdominal radiography findings may lead to underestimates of the infectious process.
    • Imaging studies more sensitive than radiography, such as chest CT, may define the infectious process better than radiography.
    • Appropriate cultures are obtained from suspected infectious sites. Although inflammatory cells are decreased to absent, microorganisms can be identified.

Imaging Studies

  • No specific radiographic studies are necessary to make a diagnosis.
  • As previously discussed, imaging studies are useful in diagnosing infections.

Histologic Findings

  • The most striking finding in biopsies of infections in patients with all forms of LAD is the absence of neutrophils and other inflammatory cells.

More on Complement Receptor Deficiency

Overview: Complement Receptor Deficiency
Differential Diagnoses & Workup: Complement Receptor Deficiency
Treatment & Medication: Complement Receptor Deficiency
Follow-up: Complement Receptor Deficiency
Multimedia: Complement Receptor Deficiency
References
[ CLOSE WINDOW ]

References

  1. Paccaud JP, Carpentier JL, Schifferli JA. Difference in the clustering of complement receptor type 1 (CR1) on polymorphonuclear leukocytes and erythrocytes: effect on immune adherence. Eur J Immunol. Feb 1990;20(2):283-9. [Medline].

  2. Wakabayashi M, Ohi H, Tamano M, Onda K, Fujita T, Tomino Y. Acquired loss of erythrocyte complement receptor type 1 in patients with diabetic nephropathy undergoing hemodialysis. Nephron Exp Nephrol. 2006;104(3):e89-e95. [Medline].

  3. Cherukuri A, Cheng PC, Pierce SK. The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. J Immunol. Jul 1 2001;167(1):163-72. [Medline].

  4. Tenner AJ. Membrane receptors for soluble defense collagens. Curr Opin Immunol. Feb 1999;11(1):34-41. [Medline].

  5. Drouin SM, Kildsgaard J, Haviland J, et al. Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma. J Immunol. Feb 1 2001;166(3):2025-32. [Medline].

  6. Wetsel RA. Structure, function and cellular expression of complement anaphylatoxin receptors. Curr Opin Immunol. Feb 1995;7(1):48-53. [Medline].

  7. Etzioni A, Harlan JM. Cell adhesion and leukocyte defects. In: Ochs HS, Smith, CIE, Puck JM. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. 2nd ed. New York, NY: Oxford University Press, Inc; 2007:550-64.

  8. Anderson DC, Schmalsteig FC, Finegold MJ, et al. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. Oct 1985;152(4):668-89. [Medline].

  9. Arnaout MA, Dana N, Gupta SK, Tenen DG, Fathallah DM. Point mutations impairing cell surface expression of the common beta subunit (CD18) in a patient with leukocyte adhesion molecule (Leu-CAM) deficiency. J Clin Invest. Mar 1990;85(3):977-81. [Medline].

  10. Marquardt T, Brune T, Luhn K, et al. Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism. J Pediatr. Jun 1999;134(6):681-8. [Medline].

  11. Marquardt T, Luhn K, Srikrishna G, et al. Correction of leukocyte adhesion deficiency type II with oral fucose. Blood. Jun 1999;94(12):3976-85. [Medline].

  12. Yakubenia S, Wild MK. Leukocyte adhesion deficiency II. Advances and open questions. FEBS J. Oct 2006;273(19):4390-8. [Medline].

  13. Helmus Y, Denecke J, Yakubenia S, et al. Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter. Blood. May 15 2006;107(10):3959-66. [Medline].

  14. Alon R, Etzioni A. LAD-III, a novel group of leukocyte integrin activation deficiencies. Trends Immunol. Oct 2003;24(10):561-6. [Medline].

  15. Kinashi T, Aker M, Sokolovsky-Eisenberg M, et al. LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds. Blood. Feb 1 2004;103(3):1033-6. [Medline].

  16. Etzioni A, Alon R. Leukocyte adhesion deficiency III: a group of integrin activation defects in hematopoietic lineage cells. Curr Opin Allergy Clin Immunol. Dec 2004;4(6):485-90. [Medline].

  17. Etzioni A, Doerschuk CM, Harlan JM. Of man and mouse: leukocyte and endothelial adhesion molecule deficiencies. Blood. Nov 15 1999;94(10):3281-8. [Medline].

  18. Ambruso DR, Knall C, Abell AN, et al. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci USA. Apr 25 2000;97(9):4654-9. [Medline].

  19. Williams DA, Tao W, et al. Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood. Sep 1 2000;96(5):1646-54. [Medline].

  20. DeLisser HM, Christofidou-Solomidou M, Sun J, Nakada MT, Sullivan KE. Loss of endothelial surface expression of E-selectin in a patient with recurrent infections. Blood. Aug 1 1999;94(3):884-94. [Medline].

  21. Kuijpers TW, van Bruggen R, Kamerbeek N, et al. Natural history and early diagnosis of LAD-1/variant syndrome. Blood. Apr 15 2007;109(8):3529-37. [Medline].

  22. [Best Evidence] Joshi AY, Iyer VN, Hagan JB, St Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009;84(1):16-22. [Medline].

  23. [Guideline] Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. May 2005;94(5 Suppl 1):S1-63. [Medline].

  24. Stary J, Bartunkova J, Kobylka P, et al. Successful HLA-identical sibling cord blood transplantation in a 6-year-old boy with leukocyte adhesion deficiency syndrome. Bone Marrow Transplant. Jul 1996;18(1):249-52. [Medline].

  25. Thomas C, Le Deist F, Cavazzana-Calvo M, et al. Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency. Blood. Aug 15 1995;86(4):1629-35. [Medline].

  26. Elhasid R, Rowe JM. Hematopoetic Stem Cell Transplantation in Neutrophil Disorders: Severe Congenital Neutropenia, Leukocyte Adhesion Deficiency and Chronic Granulomatous Disease. Clin Rev Allergy Immunol. May 19 2009;[Medline].

  27. Qasim W, Cavazzana-Calvo M, Davies EG, et al. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency. Pediatrics. Mar 2009;123(3):836-40. [Medline].

  28. Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175-94. [Medline].

  29. Le Deist F, Blanche S, Keable H, et al. Successful HLA nonidentical bone marrow transplantation in three patients with the leukocyte adhesion deficiency. Blood. Jul 1989;74(1):512-6. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

complement receptor deficiency, leukocyte adhesion deficiency, LAD, LAD I (CD18) deficiency, LAD II deficiency, LAD III deficiency, CR1 (CD35) deficiency, systemic lupus erythematosus, hemodialysis, preeclampsia, skin infections, periodontitis, gingivitis, mental retardation, distinctive facies, short stature, bone marrow transplantation, urinary tract infection, ear infection, otitis media, ulcerative stomatitis, necrotic cutaneous abscesses, cellulitis, omphalitis, pneumonia, aseptic meningitis, chronic granulomatous disease, treatment, diagnosis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Alan P Knutsen, MD, Professor of Pediatrics, Director of Pediatric Allergy and Immunology, 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 and Clinical Immunology Society
Disclosure: Nothing to disclose.

Medical Editor

Ann O'Neill Shigeoka, MD †, Former Clinical Associate Professor, Department of Pediatrics, Division of Immunology-Rheumatology, University of Utah School of Medicine
Ann O'Neill Shigeoka, MD † is a member of the following medical societies: American Federation for Medical Research, Clinical Immunology Society, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville
David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology
Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD, Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School
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 Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.