Leukocyte adhesion deficiency type 1 (LAD-1)/variant. A novel immunodeficiency syndrome characterized by dysfunctional beta2 integrins

J Clin Invest. 1997 Oct 1;100(7):1725-33. doi: 10.1172/JCI119697.

Abstract

Leukocyte adhesion deficiency (LAD) is characterized by the inability of leukocytes, in particular neutrophilic granulocytes, to emigrate from the bloodstream towards sites of inflammation. Infectious foci are nonpurulent and may eventually become necrotic because of abnormal wound healing. LAD-1 is characterized by the absence of the beta2 integrins (CD11/CD18) on leukocytes. When expression is completely absent, patients often die within the first year. However, low levels of beta2 expression may result in a milder clinical picture of recurrent infection, which offers a better prognosis. In this paper, we describe the in vivo and in vitro findings on a patient with clinical features of a mild LAD-1 disorder, i.e., suffering from bacterial infections without apparent pus formation in the presence of a striking granulocytosis, showing no delayed-type hypersensitivity reaction upon skin testing, no specific antibody generation, but normal in vitro T cell proliferation responses after immunization. Expression levels of CD11/CD18 proteins were completely normal, but leukocyte activation did not result in CD11/ CD18 activation and high-avidity ligand-binding. In vitro chemotaxis and endothelial transmigration of the neutrophils as well as leukocyte aggregation responses were almost absent. On the other hand, beta1 and beta3 integrin-mediated adhesion functions were completely normal. During follow-up, a bleeding tendency related to decreased beta3 activation became clinically apparent, different from previously described cellular adhesion molecule variants. Therefore, this is the first well-documented case of a clinical combined immunodeficiency syndrome that results from nonfunctional CD11/CD18 molecules, and thus designated LAD-1/ variant.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology
  • CD11 Antigens / analysis
  • CD18 Antigens / analysis
  • CD18 Antigens / genetics
  • CD18 Antigens / immunology*
  • Cell Adhesion
  • Cell Aggregation
  • Chemotaxis, Leukocyte
  • Clone Cells
  • Hemorrhage
  • Humans
  • Infant
  • Integrin beta1 / immunology
  • Integrin beta3
  • Integrins / immunology*
  • Leukocyte-Adhesion Deficiency Syndrome / diagnosis
  • Leukocyte-Adhesion Deficiency Syndrome / immunology*
  • Lymphocyte Activation
  • Male
  • Neutrophil Activation
  • Platelet Aggregation
  • Platelet Membrane Glycoproteins / immunology
  • Sequence Analysis, DNA
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD
  • CD11 Antigens
  • CD18 Antigens
  • Integrin beta1
  • Integrin beta3
  • Integrins
  • Platelet Membrane Glycoproteins