Laboratory Studies

See the list below:

In leukocyte adhesion deficiency (LAD), the CBC count typically reveals leukocytosis (WBC count >20 X 10⁹/L) in the absence of infection; leukocytosis dramatically increases with infection (WBC counts of 40-100 X 10⁹/L are common).
Flow cytometry is used to assess the presence of the β2 integrins CD11a/CD18 (LFA-1 or aL/b2) on leukocytes, CD11b/CD18 (Mac-1 or aM/b2) on myeloid cells, and CD11c/CD18 (p150,95 or aX/b2) on myeloid cells.
In leukocyte adhesion deficiency II, the Bombay blood group phenotype is detected.
Preimplantation genetic diagnosis (PGD) of leukocyte adhesion deficiency I offers promise. The application of preimplantation genetic diagnosis has been developed to achieve a healthy pregnancy in one child.^[9]Thus, some evidence suggests that, for couples carrying mutated genes, traditional prenatal diagnosis and the decision of whether to terminate a pregnancy might not be acceptable because the application of PGD provides an alternative.

Imaging Studies

See the list below:

CT scanning and MRI are essential for diagnosis of abdominal infections in these patients because of the defective phagocytic mobilization to the site of infection. Plain radiographic findings are often misleading because of the absence of pus or lobar consolidation in pneumonia.
Bone scanning and gallium scanning may be useful modalities in localizing infection in selected patients. Because gallium relies on the presence of phagocytic cells, gallium scan findings are most likely to be informative when patients with leukocyte adhesion deficiency have residual expression of integrins or when granulocytes are transfused to patients with severe leukocyte adhesion deficiency (absence of CD18 expression).

Other Tests

See the list below:

In leukocyte adhesion deficiency I, assays of random migration, chemotaxis, phagocytosis, and killing by neutrophils invariably show deficits in these functions. Phagocytic and killing defects are caused by the impaired recognition of iC3b-opsonized organisms. Antibody-mediated cellular cytotoxicity is also impaired.
In leukocyte adhesion deficiency I, lymphocyte functions requiring LFA-1 (the CD2 pathway) are impaired; mitogen responses may be decreased. The relationship of in vitro lymphocyte defects to clinical infections is not understood. Although antibody responses to the T-dependent phiX174 bacteriophage were found to be impaired, immunoglobulin levels and specific antibody responses to vaccines are typically normal.
Leukocyte adhesion deficiency II is not associated with defects in lymphocyte or antibody function. The decrease in biochemical activity of guanosine 5'-diphosphate-D-mannose dehydratase (GMD) may be measured.

Procedures

See the list below:

Bronchoscopy may be required to identify the etiology of pulmonary infection.
Spinal taps have been carried out without complication.
Surgical procedures are fraught with difficulty caused by the extremely delayed healing. In the author's experience, wet-to-dry dressing changes are successful in promoting healing; granulocyte transfusions were not clinically successful.

Histologic Findings

See the list below:

In both leukocyte adhesion deficiency I and leukocyte adhesion deficiency II, localized infections lack neutrophilic infiltrates or pus formation; edema and necrosis are the prominent findings.

Treatment & Management

[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. [QxMD MEDLINE Link].
Hanna S, Etzioni A. Leukocyte adhesion deficiencies. Ann N Y Acad Sci. 2012 Feb. 1250(1):50-5. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Alon R, Etzioni A. LAD-III, a novel group of leukocyte integrin activation deficiencies. Trends Immunol. 2003 Oct. 24(10):561-6. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link]. [Full Text].
Bauer TR Jr, Hickstein DD. Gene therapy for leukocyte adhesion deficiency. Curr Opin Mol Ther. 2000 Aug. 2(4):383-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Eklund EA, Freeze HH. The congenital disorders of glycosylation: a multifaceted group of syndromes. NeuroRx. 2006 Apr. 3(2):254-63. [QxMD MEDLINE Link].
Etzioni A. Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options. Adv Exp Med Biol. 2007. 601:51-60. [QxMD MEDLINE Link].
Etzioni A, Doerschuk CM, Harlan JM. Of man and mouse: leukocyte and endothelial adhesion molecule deficiencies. Blood. 1999 Nov 15. 94(10):3281-8. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Etzioni A, Tonetti M. Fucose supplementation in leukocyte adhesion deficiency type II. Blood. 2000 Jun 1. 95(11):3641-3. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
McDowall A, Inwald D, Leitinger B, et al. A novel form of integrin dysfunction involving beta1, beta2, and beta3 integrins. J Clin Invest. 2003 Jan. 111(1):51-60. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
Uzel G, Kleiner DE, Kuhns DB, Holland SM. Dysfunctional LAD-1 neutrophils and colitis. Gastroenterology. 2001 Oct. 121(4):958-64. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Wild MK, Luhn K, Marquardt T, Vestweber D. Leukocyte adhesion deficiency II: therapy and genetic defect. Cells Tissues Organs. 2002. 172(3):161-73. [QxMD MEDLINE Link].

Media Gallery

Labial ulceration from which Escherichia coli was cultured in an 8-month-old girl with leukocyte adhesion deficiency type 1 (LAD I). Note the thin bluish scar at the superior aspect of the labia from an earlier cellulitis.
This 3-year-old girl had leukocyte adhesion deficiency type I (LAD I) with complete absence of CD18 expression. Note the typical gingivostomatitis, which was culture-negative for any pathogen.
This 10-month-old patient with severe leukocyte adhesion deficiency type I (LAD I) developed a cervical adenitis caused by Klebsiella pneumoniae. Following incision and drainage, wound healing took 4 months.