lactoferrin and alpha-1-Antitrypsin-Deficiency

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.. 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)].. 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).. 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.

Topics: Adult; Aged; alpha 1-Antitrypsin Deficiency; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Antimicrobial Cationic Peptides; Blood Proteins; Case-Control Studies; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Homozygote; Humans; Infant; Lactoferrin; Leukocyte Elastase; Male; Membrane Proteins; Middle Aged; Myeloblastin; Peroxidase; Phenotype; Serine Endopeptidases; Vasculitis