Increased incidence of autoimmune markers in patients with combined pulmonary fibrosis and emphysema

Abstract

BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is an umbrella term encompassing upper lobe emphysema and lower lobe pulmonary fibrosis with pathogenesis elusive. The aim of our study was to investigate the incidence of autoimmune markers in patients with CPFE.MethodsIn this multicenter study we retrospectively evaluated records from patients with CPFE (n=40) and IPF (n=60) without emphysema. Baseline demographic characteristics, high-resolution computed tomography (HRCT), spirometry, histopathological, treatment, serum immunologic and survival data were investigated. B cell presence was estimated with CD20 immunostaining in representative lung biopsy samples from CPFE patients and control subjects.ResultsA statistically significant increased number of CPFE patients with elevated serum ANA with or without positive p-ANCA titers compared to patients with IPF without emphysema was observed. Patients with CPFE and positive autoimmune markers exhibited improved survival compared to patients with a negative autoimmune profile. A massive infiltration of clusters of CD20+ B cells forming lymphoid follicles within the fibrotic lung in CPFE patients with positive serum immunologic profile compared to patients with negative profile, was noted and positively correlated with improved survival.ConclusionsA significant proportion of patients with CPFE may present with underlying auto-immune disorders that may reside insidiously and be associated with favorable prognosis. Early identification of these patients using a panel of auto-antibodies may lead to more targeted and effective therapeutic applications.

Pulmonary fibrosis and emphysema: Is the emphysema type associated with the pattern of fibrosis?

“…Recently it has been reported that specific genes of the protease-antiprotease balance pathway may be associated with specific emphysema types, particularly MMP9 and TGFB1 to CLE and TIMP2 and TNF to PSE [31] . Autoimmunity has also been implicated in the pathogenesis of CPFE [34] . Based on these findings, one could speculate that there may be a possible pathogenetic linkage in CPFE patients leading to combinations of specific patterns of lung fibrosis and emphysema.…”

Prevalence and Responsiveness to Treatment of Lung Abnormalities on Chest Computed Tomography in Patients With Microscopic Polyangiitis: A Multicenter, Longitudinal, Retrospective Study of One Hundred Fifty Consecutive Hospital‐Based Japanese Patients

“…Even more intriguingly, a previous histopathologic analysis showed that a wide variety of extravascular pulmonary injuries, including airway lesions, can be observed in patients with AAVs (9). In addition, combined pulmonary fibrosis with emphysema (CPFE) was recently reported in patients with connective tissue diseases (10,11) and in patients with MPA or myeloperoxidase (MPO)-ANCA positivity (12,13), suggesting the more complex picture of pulmonary involvement in MPA. However, the prevalence of individual components of pulmonary involvement in consecutive patients with MPA, including those without apparent pulmonary manifestations, has not been reported.…”

The Syndrome of Combined Pulmonary Fibrosis and Emphysema

“…In one study, autoimmune markers including perinuclear anti-neutrophil cytoplasmic antibodies were more frequently found in patients with CPFE than in subjects with IPF and no emphysema, correlating with infi ltration of the fi brotic lungs by clusters of CD20+ B lymphocytes within lymphoid follicles [ 80 ]. It is speculated that anti-myeloperoxidase antibodies in microscopic polyangiitis may promote the degranulation of neutrophils, with release of reactive oxygen species that may participate to disease pathogenesis.…”