title: Analysis of anti-neutrophil cytoplasmic antibodies (ANCA): frequency and specificity in a sample of 191 homozygous (PiZZ) alpha1-antitrypsin-deficient subjects.
abstract: BACKGROUND
  ANCA are autoantibodies directed against polymorphonuclear cell antigens, mainly proteinase 3 (PR3) and myeloperoxidase (MPO), which are implicated in the pathogenesis of small-vessel necrotizing vasculitis. Alpha1-antitrypsin is the main inhibitor of neutral serine proteinase [i.e. human leukocyte elastase (HLE) and PR3] present in PMN alpha-granules (alphaGr). An association first reported by us between PR3 ANCA and the deficient PiZZ phenotype in ANCA-positive systemic vasculitis, now widely confirmed by others, led us to study the incidence and specificity of ANCA among PiZZ subjects.
  
  
  METHODS
  We tested a population of 191 PiZZ (273 sera) for ANCA activity versus 272 PiMM matched control subjects using alphaGr or antigen-specific ELISA [PR3, HLE, MPO, lactoferin (LF) and bactericidal/ permeability increasing protein (BPI)].
  
  
  RESULTS
  The incidence of antibodies directed against alphaGr and HLE but not PR3, MPO, LF or BPI was increased in the PiZZ as compared to the PiMM group (Fisher probability respectively P < 0.0001 and P < 0.05).
  
  
  CONCLUSIONS
  ANCA not directed against classical antigens (MPO and PR3) may be found in PiZZ patients. However, these patients do not develop systemic vasculitis features. Therefore, alpha1-antitrypsin deficiency is not sufficient to induce ANCA positive vasculitides, and may only act as a second hit amplifying factor.
authors.affiliation: Immunology Department, Hôtel Dieu, Nantes, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Audrain
authors.forename: R
authors.initials: R
authors.lastname: Sesboüé
authors.forename: T A
authors.initials: TA
authors.lastname: Baranger
authors.forename: J
authors.initials: J
authors.lastname: Elliott
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.forename: J P
authors.initials: JP
authors.lastname: Martin
authors.forename: C M
authors.initials: CM
authors.lastname: Lockwood
authors.forename: V L
authors.initials: VL
authors.lastname: Esnault
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D000918:Antibody Specificity; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006720:Homozygote; D006801:Humans; D007223:Infant; D007781:Lactoferrin / Q000276:immunology; D019272:Leukocyte Elastase / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D053146:Myeloblastin; D009195:Peroxidase / Q000276:immunology; D010641:Phenotype; D012697:Serine Endopeptidases / Q000276:immunology; D014657:Vasculitis / Q000235:genetics / Q000276:immunology; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D009195:Peroxidase; D007781:Lactoferrin; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; D053146:Myeloblastin