Analysis of anti-neutrophil cytoplasmic antibodies (ANCA): frequency and specificity in a sample of 191 homozygous (PiZZ) alpha1-antitrypsin-deficient subjects

Background. ANCA are autoantibodies directed. against polymorphonuclear cel l antigens, mainly proteinase 3 (PR3) and myeloperoxidase (MPO), which are implicated in the pathogenesis of small-vessel necrotizing vasculitis. Alph a1-antitrypsin is the main inhibitor of neutral serine proteinase [i.e. hum an leukocyte elastase (HLE) and PR3] present in PMN alpha-granules (alpha G r). An association first reported by us between PR3 ANCA and the deficient PiZZ phenotype in ANCA-positive systemic vasculitis, now widely confirmed b y 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 ve rsus 272 PiMM matched control subjects using aGr or antigen-specific ELISA [PR3, PILE, MPO, lactoferin (LF) and bactericidal/permeability increasing p rotein (BPI)]. Results. The incidence of antibodies directed against alpha Gr and HLE but not PR3, MPG, LF or BPI was increased in the PiZZ as compared to the PiMM g roup (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 suffi cient to induce ANCA positive vasculitides, and may only act as a second hi t amplifying factor.