title: Alopecia areata: immunohistochemistry and ultrastructure of infiltrate and identification of adhesion molecule receptors.
abstract: BACKGROUND
  Alopecia areata (AA) is a noncicatricial alopecia with still unknown pathogenesis, but increasing evidence suggests that an immunologic process might be responsible for the disease.
  
  
  METHODS
  Nineteen patients with AA were studied with ten of them in the progressive phase of the disease and nine in the stabilized phase. Biopsies of both affected and unaffected skin were taken. For immunohistochemistry, monoclonal antibodies directed against CD3, CD4, CD8, CD10a, CD36, and HLA-DR antigens, were used, as well as antibodies directed against adhesion molecules ICAM-1, ELAM-1 and LFA-1. For electron microscopy (EM), specimens were fixed in glutaraldehyde-sodium cacodylate buffer, post-fixed in osmium tetroxide, and stained with uranyl acetate. For statistical analysis, sections from involved and uninvolved skin of each patient for each antibody, the sign test, Fisher's F-test, and the Tukey-Kramer test were used.
  
  
  RESULTS
  There was a rich infiltrate of CD4+ cells and CD1a+ cells, particularly in the perivascular zone of both unaffected and affected skin (here in the perivascular and in the peribulbar zone) in the progressive phase of AA. In the stabilized phase the infiltrate was scant, both in unaffected and affected skin and limited to the peribulbar area. Receptors of adhesion molecules (ICAM-2, ELAM-1, LFA-1) were strongly expressed, mainly at the microvascular level in both unaffected and affected skin in the progressive phase, but were only weakly or not at all expressed in the stabilized phase, again in unaffected and affected skin. Ultrastructural data confirmed the immunohistochemical findings and showed close contacts between infiltrating lymphocytes and Langerhans'-lineage cells mainly in the progressive phase.
  
  
  CONCLUSIONS
  Our results suggest that: 1) an immunologic process, apparently carried out by CD4+ lymphocytes and by dendritic CD1a+ and CD36+ cells, may play a key role at least in the early phase of the disease involving primarily microvessels and later on the bulbar area; 2) the expression of adhesion molecule receptors is involved at the beginning of the disease by mediating the adherence of leukocytes to endothelial cells and subsequent trafficking into the dermis.
authors.affiliation: Department of Dermatology, University of Florence, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Ghersetich
authors.forename: G
authors.initials: G
authors.lastname: Campanile
authors.forename: T
authors.initials: T
authors.lastname: Lotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000506:Alopecia Areata / Q000276:immunology / Q000473:pathology*; D018949:Antigens, CD1 / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D018955:CD36 Antigens / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D016827:CD8 Antigens / Q000032:analysis; D002448:Cell Adhesion; D019070:Cell Lineage; D002648:Child; D003713:Dendritic Cells / Q000473:pathology; D019040:E-Selectin / Q000032:analysis / Q000235:genetics / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000473:pathology; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000032:analysis / Q000235:genetics / Q000648:ultrastructure*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics / Q000648:ultrastructure; D007801:Langerhans Cells / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000235:genetics / Q000648:ultrastructure; D008833:Microcirculation; D008854:Microscopy, Electron; D008875:Middle Aged; D012867:Skin / Q000098:blood supply / Q000276:immunology / Q000473:pathology
chemical_list: D018949:Antigens, CD1; D017252:CD3 Complex; D018955:CD36 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D019040:E-Selectin; D006684:HLA-DR Antigens; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1