BPI-ANCA and Long-Term Prognosis among 46 Adult CF Patients: A Prospective 10-Year Follow-Up Study

Abstract

Introduction. Anti-neutrophil cytoplasmic antibodies specific for bactericidal/permeability-increasing protein (BPI-ANCA) are frequent in CF patients and mainly develop in response to infection with Pseudomonas aeruginosa. It is not known to what extent BPI-ANCA correlates to prognosis. Objectives. To evaluate the prognostic value of IgA-BPI-ANCA, measured at the beginning of the study, for transplantation-free survival. Methods. A cohort of 46 adult, nontransplanted CF patients was generated, 1995–1998, and characterized using Leeds criteria, lung function, and IgA-BPI-ANCA levels measured by ELISA. The cohort was followed until December 2009, using the combined endpoint of death or lung transplantation. Results. Lung function and IgA-BPI-ANCA, but not Leeds criteria, were significantly associated with adverse outcome. No patient with normal lung function at baseline reached endpoint. Within 10 years 8/11 with high BPI-ANCA reached an endpoint compared to 3/17 ANCA-negative patients. A similar result was seen within the Leeds I group where 7 out of 9 BPI-ANCA-positive patients reached endpoint, compared to none of the 5 patients without BPI-ANCA. Conclusions. IgA-BPI-ANCA is associated with adverse outcome among Pseudomonas aeruginosa infected CF patients, suggesting that BPI-ANCA is a biomarker of an unfavourable host-pathogen interaction.

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

“…BPI-ANCA had a higher capability of predicting these end-points (AUC = 0.77, p = 0.002) compared with serology tests: AUC for AP 0.7 P ( p = 0.02), ELA 0.65 ( p = 0.09), and ExoA 0.54 ( p = 0.6). This finding is in line with earlier results from our group [ 24 ], where BPI-ANCA level, in contrast to Leeds class, was significantly correlated with outcome. These findings suggest that BPI-ANCA is a biomarker of an unfavourable host-pathogen interaction and not merely a substitute marker for P. aeruginosa colonization.…”

“…BPI-ANCA seems to develop in response to P. aeruginosa colonization, but there are also patients colonized with P. aeruginosa who do not develop BPI-ANCA [ 22 , 24 ]. After eradication of P. aeruginosa colonization by lung transplantation a significant decrease in BPI-ANCA levels has been seen [ 22 ] and it has been shown that BPI-ANCA levels significantly decrease after sinus surgery [ 29 ].…”

“…The relation between BPI-ANCA and different P. aeruginosa serologies has not been studied so far and it is not known if BPI-ANCA yields the same set of information as P. aeruginosa serology tests. In a previous study, we found patients with chronic P. aeruginosa colonization who remained ANCA-negative for over a decade suggesting that BPI-ANCA shows something different than Pseudomonas colonization/infection or P. aeruginosa serology tests [ 24 ]. This study was performed to further analyse how BPI-ANCA differs from P. aeruginosa serology as our earlier investigations indicate that BPI-ANCA has a potential clinical use as a prognostic factor in CF.…”

Clinical significance of BPI‐ANCA detecting in COPD patients with Pseudomonas aeruginosa colonization

“…The present study detected TNF‐α, IL‐6, IL‐1β, CRP, and NEU% levels in COPD patients with P aeruginosa colonization and found that inflammatory markers were higher in patients seropositive for BPI‐ANCA than those negative, indicating a link between BPI‐ANCA positivity and inflammatory status in COPD patients with P aeruginosa colonization. A 10‐year study followed 46 patients with cystic fibrosis and P aeruginosa colonization drawn conclusion basically consistent with us—it showed that 15/28 BPI‐ANCA(+) patients developed adverse outcomes ( P = 0.01), while only 2/18 BPI‐ANCA(−) patients did so, suggesting the close association of inflammation and poor prognosis in COPD patients with P aeruginosa colonization with serum BPI‐ANCA positivity. Besides, pulmonary function test showed that indices including FEV 1 %pred and FEV 1 /FVC (%) decreased significantly in COPD patients with P aeruginosa colonization positive for BPI‐ANCA, which is basically consistent with the findings of Seema Singh et al…”

Factors Affecting Prognosis and Prediction of Outcome in Cystic Fibrosis Lung Disease

“…Levels of BPI-ANCA correlate strongly with markers of lung disease and it may indicate a pathogenic role in CF [121] and a recent study has shown that the presence of BPI-ANCA correlated significantly with a poor outcome, being death or requiring a lung transplantation. Furthermore, in patients colonised with PA the outcome was significantly worse if associated with this biomarker [122].…”