Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronicpulmonary infection/inflammation which leads to respiratory failure. Thepresence of anti-neutrophil cytoplasmic autoantibodies (ANCA) haspreviously been observed in the sera of patients with CF. In view of theknown relationship of ANCA with primary vasculitis and of their putativepathogenetic role in these disorders, we studied the presence, specificityand isotype of ANCA and their clinical associations in 66 adult CFpatients. None of the 66 CF samples had autoantibodies to the major ANCAantigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samplescontained IgG and 55/66 (83%) IgA, autoantibodies tobactericidal/permeability increasing protein (BPI), a recentlycharacterized ANCA specificity. All the IgA anti-BPI-positive samples werealso IgG anti-BPI-positive. The autoantibody specificity was confirmed byinhibition assay and immunoblotting of CF sera against a neutrophil granulepreparation. Furthermore, in this cross-sectional study, anti-BPI levelswere inversely correlated with the observed reductions in FEV1 and FVC (IgAanti-BPI and FEV1: r = 0.508, p < 0.0001), andboth IgG and IgA anti-BPI levels were higher in CF patients with secondaryvasculitis (n = 6) than in those without(p < 0.05). ANCA with specificity for BPI werepresent in the majority of CF sera in this study and autoimmune processesmay be associated with the development of pulmonary injury in CF.