BPI-ANCA Provides Additional Clinical Information to Anti-PseudomonasSerology: Results from a Cohort of 117 Swedish Cystic Fibrosis Patients

Abstract

Patients with cystic fibrosis (CF) colonized with Pseudomonas aeruginosa (P. aeruginosa) have worse prognosis compared with patients who are not. BPI-ANCA is an anti-neutrophil cytoplasmic antibody against BPI (bactericidal/permeability increasing protein) correlating with P. aeruginosa colonization and adverse long time prognosis. Whether it provides additional information as compared to standard anti-P. aeruginosa serology tests is not known. 117 nontransplanted CF patients at the CF centre in Lund, Sweden, were followed prospectively for ten years. Bacterial colonisation was classified according to the Leeds criteria. IgA BPI-ANCA was compared with assays for antibodies against alkaline protease (AP), Elastase (ELA), and Exotoxin A (ExoA). Lung function and patient outcome, alive, lung transplanted, or dead, were registered. BPI-ANCA showed the highest correlation with lung function impairment with an r-value of 0.44. Forty-eight of the 117 patients were chronically colonized with P. aeruginosa. Twenty of these patients experienced an adverse outcome. Receiver operator curve (ROC) analysis revealed that this could be predicted by BPI-ANCA (AUC = 0.77), (p = 0.002) to a better degree compared with serology tests. BPI-ANCA correlates better with lung function impairment and long time prognosis than anti-P. aeruginosa serology and has similar ability to identify patients with chronic P. aeruginosa.

Prevalence of Bactericidal/Permeability-Increasing Protein Autoantibodies in Cystic Fibrosis Patients: Systematic Review and Meta-Analysis

“…Bacterial colonization in respiratory secretions was defined by the Leeds criteria; the determination of antibodies against BPI was analyzed by ELISA. 3 However, the study did not report upper cutoff values for their ELISA technique. Thirty-one percent of the patients in this study were positive for BPI-ANCA.…”

“…These antibodies have been identified in several diseases, including CF, inflammatory bowel diseases, vasculitis, rheumatoid arthritis, and primary sclerosing cholangitis and often develop in CF patients after colonization by more virulent strains of P. aeruginosa. [3][4][5][6] During the last decade, several studies have reported varying prevalence rates of BPI-ANCA in CF patients and its link to a poor prognosis secondary to a progressive deterioration in lung function. 3,[6][7][8][9] The largest study reported by Carlsson et al was a cross-sectional study of BPI-ANCA association with P. aeruginosa colonization and its effect on lung function in 366 CF patients (age: 0.5-55 years) and had a prevalence rate of 62.8%.…”

“…[3][4][5][6] During the last decade, several studies have reported varying prevalence rates of BPI-ANCA in CF patients and its link to a poor prognosis secondary to a progressive deterioration in lung function. 3,[6][7][8][9] The largest study reported by Carlsson et al was a cross-sectional study of BPI-ANCA association with P. aeruginosa colonization and its effect on lung function in 366 CF patients (age: 0.5-55 years) and had a prevalence rate of 62.8%. 10 We systematically reviewed literature that provides information on the prevalence of BPI-ANCA in patients with CF to determine a more exact estimate of the frequency of this antibody in patients with CF.…”

Autoimmunity in cystic fibrosis: significance and clinical implications

“…ANCA with BPI specificity (BPI-ANCA) have been identified in a variety of diseases, such as cystic fibrosis, inflammatory bowel diseases, vasculitis, rheumatoid arthritis, and primary sclerosing cholangitis. 3,6,13 The occurrence of BPI-ANCA in CF patients appears to develop after colonization by pathogenic strains of P. aeruginosa. 7 In the studies reviewed, a commercially available indirect immuno-fluorescence was used for ANCA testing, followed by BPI specificity test using enzymelinked immunosorbent assay (ELISA).…”

“…2 Chronic infections with P. aeruginosa develop in most CF patients, and in many CF clinics 60-80% of the adult patients are colonized with this specific pathogen. 3 In the majority of CF patients, chronic infection is preceded by intermittent colonization. Several studies have underlined the high frequency of antineutrophil cytoplasmic antibodies (ANCA) in CF patients, especially those with anti-bactericidal/permeability-increasing protein (BPI) specificity (BPI-ANCA), and their link with pulmonary infections and poor respiratory function.…”