eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Complement Receptor Deficiency: Treatment & Medication

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

Treatment

Medical Care

In the severe phenotype of leukocyte adhesion deficiency (LAD) type 1, the prognosis for long-term survival is poor.7 Immune reconstitution with hematopoietic stem cell transplantation is the treatment of choice.24,25,26,27 Numerous stem cell donor choices, human leukocyte antigen (HLA)–matched related bone marrow, HLA-matched cord blood, and HLA-matched unrelated bone marrow, have been successfully used to immune reconstitute patients with LAD type 1. Preexisting infections, which are common, must be successfully treated before transplantation. Patients with preexisting infections may need surgical drainage, debridement, and intravenous antibiotics.

The bone marrow in patients with LAD is hyperplastic, and some T-cell function is present. Therefore, myeloablative treatment to make room in the bone marrow and immunosuppressive therapy to prevent graft rejection has been used. The absence of LFA-1 on host's cells that cause decreased T-cell function, T-cell cytotoxicity, and natural killer (NK) cell cytotoxicity may actually facilitate engraftment. Both acute and chronic graft versus host disease (GVHD) have been a problem in patients with LAD even when an HLA-matched sibling donor is used.

  • Treatment of infections in patients with the severe phenotype of LAD type 1 can be difficult.
    • Treatment often requires appropriate intravenous antibiotics.
    • Surgical drainage of abscesses and surgical debridement of infected necrotic tissue is often required.
    • Some patients have undergone amputation of limbs to control infected bone.
    • The gingivitis and periodontitis that occurs in all forms of LAD often requires surgery, sometimes with removal of dentition.
    • Because of poor wound healing, complications such as fistulas may occur. Therefore, surgical care is complex as well.
    • Infections in patients with the moderate phenotype of LAD type 1 can often be treated with oral antibiotics.
  • LAD type 2 is a metabolic defect of fucose metabolism that affects all fucosylated molecules, including sialyl-Lewis X, which is deficient in LAD type 2.
    • The biochemical activity of GDP-D-mannose-4,6 dehydratase (GMD) that converts mannose to fucose is decreased in patients with LAD type 2. However, the primary defect is thought to be a GMD-regulating protein.
    • Erythrocyte fucosylated H antigens are also absent in LAD type 2 (Bombay phenotype).
  • Oral fucose supplementation has been successful in the treatment of patients with LAD type 2, with correction of expression CD15s on neutrophils.11 Elevated neutrophil cell counts returned to the reference range, and clinical improvement was achieved with reduction of infections.
    • Patients with LAD type 2 were treated with 5 doses of fucose per day, starting at 25 mg/kg, which was slowly increased to 492 mg/kg.
    • After 40 days of fucose 140 mg/kg, levels of E-selectins, P-selectins, and CD15s reached approximately 50% the reference range.
    • Neutrophil counts decreased to the reference range.
    • H antigens on erythrocytes did not reappear.
    • Of importance, psychomotor development may also improve.

Surgical Care

Consultation with an oral surgeon is necessary for most patients with any form of LAD. Consultation with a surgeon for surgical drainage and necrotic tissue debridement is ordered as indicated for patients with LAD.

Consultations

Diagnosis and management of LAD should be referred to a hematologist and/or an immunologist. A hematologist or an immunologist skilled in bone marrow transplantation should perform this procedure.

Consultation with an oral surgeon is necessary for most patients with any form of LAD. Consultations to obtain appropriate cultures are often needed. This may include a pulmonologist to perform bronchoalveolar lavage (BAL), a surgeon to perform abscess aspirates, and an otolaryngologist to perform myringotomy or sinus aspirates. Consultation with an infectious diseases specialist may be indicated to select appropriate antibiotic coverage.

Diet

In LAD type 1, no dietary restrictions are necessary. In LAD type 2, fucose dietary supplementation is indicated.

Activity

Activity is not restricted.

Medication

Patients with leukocyte adhesion deficiency (LAD) type 1 are susceptible to various bacterial infections. To direct appropriate antibiotic therapy, obtaining cultures from infectious sites is essential. Infections with Staphylococcus, Pseudomonas, Klebsiella, and Enterococcus species and E coli are common. Therefore, antibiotic coverage of these organisms may be initiated until the specific organism is identified and sensitivity is completed.

Although some patients have been treated with prophylactic antibiotics, their use in LAD has not been demonstrated. Immunizations should be continued in these patients because antibody responses are present although abnormal.

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
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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].

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Further Reading

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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

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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.

 
 
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