Leukocyte Adhesion Deficiency Follow-up
- Author: Stephen J Nervi, MD; Chief Editor: Harumi Jyonouchi, MD more...
Further Outpatient Care
See the list below:
- Scrupulous follow-up of infections is necessary for patients with leukocyte adhesion deficiency.
- As noted above, outpatient management of infections has become customary despite the complexity of care and the stress to families.
Further Inpatient Care
See the list below:
- Leukocyte adhesion deficiency type I (LAD I) is often associated with life-threatening infections requiring intensive care. Coordinating medical management between immunologists, infectious disease specialists, pulmonologists, and surgical specialists is challenging.
- Excellent laboratory and radiology support mandates hospitalization in tertiary children's medical centers.
Inpatient & Outpatient Medications
See the list below:
- Patients with leukocyte adhesion deficiency I are at risk for fungal infections with Candida species because of their frequent need for broad-spectrum antibiotics.
See the list below:
- Most clinical immunologists strongly believe that the great complexity of medical problems for any primary immunodeficiency disease requires the patient to be managed by an immunologist.
- The subtle signs of infection, the need to offer stem cell transplantation, and the early deaths in patients with leukocyte adhesion deficiency I that is not properly treated suggest that frequent monitoring by a clinical immunologist is essential.
- The major services for transfer are the intensive care and surgical teams.
See the list below:
- Prenatal diagnosis for leukocyte adhesion deficiency I is possible by chorionic villus sampling or amniocentesis using DNA methodology in families where the exact mutations have been established. Fetal blood sampling and fluorocytometric testing for the presence of CD18 on lymphocytes, monocytes, and neutrophils can establish the diagnosis when DNA analysis is not available.
- In leukocyte adhesion deficiency II, ultrasonography for growth retardation, skeletal abnormalities, and distinctive facial features can establish the diagnosis prenatally in some families.
See the list below:
- Patients with leukocyte adhesion deficiency I are at risk for graft versus host disease post–stem cell reconstitution, although graft versus host disease has been less common than in other transplantation settings.
- Patients with leukocyte adhesion deficiency II experience growth failure and mental retardation, although they are less likely to die of infection. Reports of these patients are so rare that other complications may not be observed adequately yet.
See the list below:
- Without hematopoietic stem cell transplantation (HSCT), patients with leukocyte adhesion deficiency I who have an absence of CD18 expression usually die from infection within 2 years of life. The published experience with hematopoietic stem cell transplantation has been excellent with complete immunologic reconstitution. Earlier reviews of leukocyte adhesion deficiency I indicated that unreconstituted patients most often succumbed to bacterial infections. In the author's experience, early recognition and aggressive therapy of bacterial and fungal infections is usually successful. In contrast, no specific therapy is available for the crouplike infections of suspected viral etiology or for aseptic meningitis.
- Patients with leukocyte adhesion deficiency II show severe developmental delay, which has not been significantly prevented even when fucose replacement seemed to decrease infections and improve phagocytic functions.
See the list below:
- The inability to easily detect infection is extremely stressful to families. Aggressive and complicated antibiotic and surgical care may be required for prolonged periods in the home setting, adding further stress.
- Adequate informed consent for stem cell reconstitution must review the high risk for life-threatening infection during the preparative myeloablative regimen in addition to the risk for failure to engraft and graft versus host disease. Although successful complete immune reconstitution from bone marrow transplantation is reported using fully matched related and unrelated donors or haploidentical donors (ie, parents), patients with leukocyte adhesion deficiency I cannot be guaranteed to have benign courses.
- The Immune Deficiency Foundation (some states have local chapters) is an important resource for education and for support for patients and families with any primary immunodeficiency disease. The current address is as follows: 25 W. Chesapeake Ave, Suite 206
- Towson, MD 21204
- Phone number: 877-666-0866
- Web site: www.primaryimmune.org
- The Jeffrey Modell Foundation also provides educational support and raises funds for research. The current address is as follows: 747 3rd Ave
- New York, NY 10017
- Phone: 800-JEFF-844
- Web site: www.jmfworld.org
[Guideline] Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005 May. 94(5 Suppl 1):S1-63. [Medline].
Hanna S, Etzioni A. Leukocyte adhesion deficiencies. Ann N Y Acad Sci. 2012 Feb. 1250(1):50-5. [Medline].
Cagdas D, Yilmaz M, Kandemir N, Tezcan I, Etzioni A, Sanal O. A Novel Mutation in Leukocyte Adhesion Deficiency Type II/CDGIIc. J Clin Immunol. 2014 Nov. 34(8):1009-14. [Medline].
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. 1985 Oct. 152(4):668-89. [Medline].
Helmus Y, Denecke J, Yakubenia S, et al. Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter. Blood. 2006 Feb 2. [Medline].
Alon R, Etzioni A. LAD-III, a novel group of leukocyte integrin activation deficiencies. Trends Immunol. 2003 Oct. 24(10):561-6. [Medline].
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. 2004 Feb 1. 103(3):1033-6. [Medline]. [Full Text].
McDowall A, Svensson L, Stanley P, Patzak I, Chakravarty P, Howarth K, et al. Two mutations in the KINDLIN3 gene of a new leukocyte adhesion deficiency III patient reveal distinct effects on leukocyte function in vitro. Blood. 2010 Jun 10. 115(23):4834-42. [Medline].
Lorusso F, Kong D, Jalil AK, et al. Preimplantation genetic diagnosis of leukocyte adhesion deficiency type I. Fertil Steril. 2006 Feb. 85(2):494.e15-8. [Medline].
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. 2009 May 19. [Medline].
Stepensky PY, Wolach B, Gavrieli R, Rousso S, Ben Ami T, Goldman V, et al. Leukocyte Adhesion Deficiency Type III: Clinical Features and Treatment With Stem Cell Transplantation. J Pediatr Hematol Oncol. 2014 Jul 28. [Medline].
Moutsopoulos NM, Konkel J, Sarmadi M, Eskan MA, Wild T, Dutzan N, et al. Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med. 2014 Mar 26. 6(229):229ra40. [Medline]. [Full Text].
Alon R, Aker M, Feigelson S, et al. A novel genetic leukocyte adhesion deficiency in subsecond triggering of integrin avidity by endothelial chemokines results in impaired leukocyte arrest on vascular endothelium under shear flow. Blood. 2003 Jun 1. 101(11):4437-45. [Medline]. [Full Text].
Bauer TR Jr, Hickstein DD. Gene therapy for leukocyte adhesion deficiency. Curr Opin Mol Ther. 2000 Aug. 2(4):383-8. [Medline].
Bauer TR, Gu YC, Tuschong LM, et al. Nonmyeloablative hematopoietic stem cell transplantation corrects the disease phenotype in the canine model of leukocyte adhesion deficiency. Exp Hematol. 2005 Jun. 33(6):706-12. [Medline].
Bunting M, Harris ES, McIntyre TM, Prescott SM, Zimmerman GA. Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands. Curr Opin Hematol. 2002 Jan. 9(1):30-5. [Medline].
DeLisser HM, Christofidou-Solomidou M, Sun J, et al. Loss of endothelial surface expression of E-selectin in a patient with recurrent infections. Blood. 1999 Aug 1. 94(3):884-94. [Medline].
Eklund EA, Freeze HH. The congenital disorders of glycosylation: a multifaceted group of syndromes. NeuroRx. 2006 Apr. 3(2):254-63. [Medline].
Etzioni A. Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options. Adv Exp Med Biol. 2007. 601:51-60. [Medline].
Etzioni A, Frydman M, Pollack S, et al. Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med. 1992 Dec 17. 327(25):1789-92. [Medline].
Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. Ochs HD, Puck JM, Smith CI, eds. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. Oxford University Press Inc; 1998. 375-88.
Etzioni A, Sturla L, Antonellis A, et al. Leukocyte adhesion deficiency (LAD) type II/carbohydrate deficient glycoprotein (CDG) IIc founder effect and genotype/phenotype correlation. Am J Med Genet. 2002 Jun 15. 110(2):131-5. [Medline].
Farinha NJ, Duval M, Wagner E, et al. Unrelated bone marrow transplantation for leukocyte adhesion deficiency. Bone Marrow Transplant. 2002 Dec. 30(12):979-81. [Medline].
Fiorini M, Vermi W, Facchetti F, et al. Defective migration of monocyte-derived dendritic cells in LAD-1 immunodeficiency. J Leukoc Biol. 2002 Oct. 72(4):650-6. [Medline].
Gu YC, Bauer TR Jr, Ackermann MR, et al. The genetic immunodeficiency disease, leukocyte adhesion deficiency, in humans, dogs, cattle, and mice. Comp Med. 2004 Aug. 54(4):363-72. [Medline].
Harris ES, Shigeoka AO, Li W, et al. A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by beta1 and beta2 integrins. Blood. 2001 Feb 1. 97(3):767-76. [Medline]. [Full Text].
Hidalgo A, Ma S, Peired AJ, Weiss LA, et al. Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene. Blood. 2003 Mar 1. 101(5):1705-12. [Medline]. [Full Text].
Hixson P, Smith CW, Shurin SB, Tosi MF. Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1. Blood. 2004 Feb 1. 103(3):1105-13. [Medline]. [Full Text].
Hogg N, Stewart MP, Scarth SL, et al. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest. 1999 Jan. 103(1):97-106. [Medline].
Kurkchubasche AG, Panepinto JA, Tracy TF Jr, et al. Clinical features of a human Rac2 mutation: a complex neutrophil dysfunction disease. J Pediatr. 2001 Jul. 139(1):141-7. [Medline].
Luhn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D. The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat Genet. 2001 May. 28(1):69-72. [Medline].
Malawista SE, de Boisfleury Chevance A, et al. Chemotaxis of non-compressed blood polymorphonuclear leukocytes from an adolescent with severe leukocyte adhesion deficiency. Am J Hematol. 2003 Jun. 73(2):115-20. [Medline].
Mancias C, Infante AJ, Kamani NR. Matched unrelated donor bone marrow transplantation in leukocyte adhesion deficiency. Bone Marrow Transplant. 1999 Dec. 24(11):1261-3. [Medline].
Marquardt T, Brune T, Luhn K, et al. Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism. J Pediatr. 1999 Jun. 134(6):681-8. [Medline].
Marquardt T, Luhn K, Srikrishna G, et al. Correction of leukocyte adhesion deficiency type II with oral fucose. Blood. 1999 Dec 15. 94(12):3976-85. [Medline].
Pasvolsky R, Feigelson SW, Kilic SS, et al. A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets. J Exp Med. 2007 Jul 9. 204(7):1571-82. [Medline].
Roos D, Meischl C, de Boer M, et al. Genetic analysis of patients with leukocyte adhesion deficiency: genomic sequencing reveals otherwise undetectable mutations. Exp Hematol. 2002 Mar. 30(3):252-61. [Medline].
Shaw JM, Al-Shamkhani A, Boxer LA, et al. Characterization of four CD18 mutants in leucocyte adhesion deficient (LAD) patients with differential capacities to support expression and function of the CD11/CD18 integrins LFA-1, Mac-1 and p150,95. Clin Exp Immunol. 2001 Nov. 126(2):311-8. [Medline].
Sturla L, Fruscione F, Noda K, et al. Core fucosylation of N-linked glycans in leukocyte adhesion deficiency/congenital disorder of glycosylation IIc fibroblasts. Glycobiology. 2005 Oct. 15(10):924-34. [Medline].
Sturla L, Rampal R, Haltiwanger RS, et al. Differential terminal fucosylation of N-linked glycans versus protein O-fucosylation in leukocyte adhesion deficiency type II (CDG IIc). J Biol Chem. 2003 Jul 18. 278(29):26727-33. [Medline]. [Full Text].
Uzel G, Kleiner DE, Kuhns DB, Holland SM. Dysfunctional LAD-1 neutrophils and colitis. Gastroenterology. 2001 Oct. 121(4):958-64. [Medline].
Uzel G, Tng E, Rosenzweig SD, Hsu AP, Shaw JM, Horwitz ME. Reversion mutations in patients with leukocyte adhesion deficiency type I (LAD-I). Blood. 2007 Sep 17. [Medline].
Wild MK, Luhn K, Marquardt T, Vestweber D. Leukocyte adhesion deficiency II: therapy and genetic defect. Cells Tissues Organs. 2002. 172(3):161-73. [Medline].