Anti-parietal cell autoimmunity is associated with an accelerated decline of lung function in IPF patients

Beltramo, Guillaume; Thabut, Gabriel; Péron, N.; Nicaise, Pascale; Cazes, Aurélie; Debray, Marie‐Pierre; Joannes, Audrey; Castier, Yves; Mailleux, Arnaud; Frija, Justine; Pradère, Pauline; Justet, A.; Borie, R.; Dombret, Marie-Christine; Taillé, Camille; Aubier, Michel; Crestani, Bruno

doi:10.1016/j.rmed.2017.12.011

Cited by 10 publications

(6 citation statements)

References 47 publications

(75 reference statements)

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“…Proton pump inhibitors target the H+/K+ ATPase, which has recently been shown to be expressed in the hyperplastic alveolar epithelium in patients with IPF [13]. Use of anti-acid medication has been associated with a decreased rate of decline in FVC and improved survival in some observational studies in patients with IPF [14, 15].…”

Section: Introductionmentioning

confidence: 99%

Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS® trials

et al. 2018

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BackgroundThe benefits and risks of anti-acid medication in patients with idiopathic pulmonary fibrosis (IPF) remain a topic of debate. We investigated whether use of anti-acid medication at baseline was associated with differences in the natural course of disease or influenced the treatment effect of nintedanib in patients with IPF.MethodsPost-hoc analyses of outcomes in patients receiving versus not receiving anti-acid medication (proton pump or histamine-2 receptor inhibitor) at baseline using pooled data from the two Phase III randomized placebo-controlled INPULSIS® trials of nintedanib in patients with IPF.ResultsAt baseline, 406 patients were receiving anti-acid medication (244 nintedanib; 162 placebo) and 655 were not (394 nintedanib; 261 placebo). In an analysis of the natural course of IPF by anti-acid medication use at baseline, the adjusted annual rate of decline in FVC was − 252.9 mL/year in placebo-treated patients who were receiving anti-acid medication at baseline and − 205.4 mL/year in placebo-treated patients who were not (difference of − 47.5 mL/year [95% CI: –105.1, 10.1]; p = 0.1057). In an analysis of the potential influence of anti-acid medication use on the treatment effect of nintedanib, the adjusted annual rates of decline in FVC were − 124.4 mL/year in the nintedanib group and − 252.9 mL/year in the placebo group (difference of 128.6 mL/year [95% CI: 74.9, 182.2]) in patients who were receiving anti-acid medication at baseline and − 107.0 mL/year in the nintedanib group and − 205.3 mL/year in the placebo group (difference of 98.3 mL/year [95% CI: 54.1, 142.5]) in patients who were not (treatment-by-time-by-subgroup interaction p = 0.3869). The proportions of patients who had ≥1 investigator-reported acute exacerbation were 11.7% and 5.0% in placebo-treated patients, and 4.9% and 4.8% of nintedanib-treated patients, among patients who were and were not receiving anti-acid medication at baseline, respectively.ConclusionsIn post-hoc analyses of data from the INPULSIS® trials, anti-acid medication use at baseline was not associated with a more favorable course of disease, and did not impact the treatment effect of nintedanib, in patients with IPF.Trial registrationClinicalTrials.gov identifiers: NCT01335464 and NCT01335477.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0866-0) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS® trials

et al. 2018

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“…Since we had to choose one defined condition for our experiments we expected to miss some of the possible targets. Indeed, we did not identify autoantigens that have previously been shown to be associated with disease severity or survival in IPF, such as anti-vimentin, anti heat-shock protein 70 or anti-parietal cell antibodies (Beltramo et al, 2018;Kahloon et al, 2013;Li et al, 2017;Taillé et al, 2011).…”

Section: Discussionmentioning

confidence: 70%

“…In our study, MZB1 levels correlated positively with tissue IgG and negatively with lung function parameters, suggesting a common association of IPF progression with antibody mediated autoimmunity (Schiller et al, 2017). Indeed, it has been shown that high levels of autoantibodies against vimentin (Li et al, 2017), heat-shock protein 70 (Kahloon et al, 2013), periplakin as well as anti-parietal cell antibodies (Beltramo et al, 2018; Taillé et al, 2011), were associated with a more severe disease in IPF.…”

Section: Introductionmentioning

confidence: 99%

A proteomics workflow reveals predictive autoantigens in idiopathic pulmonary fibrosis

Leuschner

Mayr

Ansari

et al. 2021

Preprint

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Rationale: The diagnosis of idiopathic pulmonary fibrosis (IPF) requires exclusion of known underlying autoimmunity, as present in interstitial lung diseases associated with connective tissue diseases (CTD-ILD). However, autoantibodies of unknown significance have been repeatedly detected in IPF patients. Objectives: We aimed to characterize autoreactivities in IPF patients beyond clinically established autoimmune panels by establishing an unbiased assay for de novo discovery of autoantigens in different forms of ILD and healthy controls. Methods: We developed the proteomic Differential Antigen Capture (DAC) assay, capturing patient antibodies from plasma, followed by affinity purification of lung proteins coupled to mass spectrometry. Plasma antibodies from patients with IPF (n=35), CTD-ILD (n=24) and age-matched controls (n=32) were analyzed and validated in an independent cohort (IPF: n=40; CTD-ILD: n=20). Plasma antibody binding profiles were associated with clinical meta-data including diagnosis, lung function and transplant free survival. Measurements and Main Results: We identified 586 putative autoantigens in both study cohorts with a broad heterogeneity among disease entities and cohorts. The prevalence of autoantibodies was higher in IPF compared to CTD-ILD. We identified a predictive autoimmune signature that was significantly associated with reduced transplant free survival in IPF. In particular, presence of autoantibodies to Thrombospondin 1 (THBS1) was associated with a significantly reduced survival in patients with IPF (p=0.002), independent of the study cohort, suggesting clinical relevance as predictive biomarker. Conclusions: Unbiased proteomic profiling reveals that the overall prevalence of autoantibodies is similar in IPF and CTD-ILD patients and identifies novel IPF specific autoantigens associated with patient survival.

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“…[32][33][34] The responsible antigen(s) remain(s) to be identified, but several studies point to the alveolar epithelial cell as a possible target of autoimmunity in IPF, as circulating autoantibodies directed toward epithelial cells have been detected by different groups [34][35][36][37][38][39][40][41] including our group. 42,43 Immune senescence due to pathologic aging may contribute to this abnormal immune status. 44 Interestingly, some genetic forms of pulmonary fibrosis are associated with autoimmunity and autoimmune disorders.…”

Section: Introductionmentioning

confidence: 99%

Antineutrophil Cytoplasmic Antibody–Associated Lung Fibrosis

Borie

Crestani

2018

Semin Respir Crit Care Med

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Pulmonary fibrosis is observed in a substantial number of patients with ANCA-associated vasculitis (AAV), 15% in a recent German series, and may be more frequent in Asian populations. ANCA are usually of anti-MPO specificity and microscopic polyangiitis is the most frequent vasculitis. Pulmonary fibrosis may increase the risk of death in patients with AAV. Treatment for AAV in patients with lung fibrosis should follow the international guidelines for vasculitis. The role of anti-fibrotic drugs (pirfenidone, nintedanib) in this condition is still unknown. Pulmonary fibrosis precedes the diagnosis of AAV or is diagnosed concomitantly in most of the cases. Interestingly, 4% to 35% of patients with pulmonary fibrosis are ANCA-positive, but only 7% to 23% of the patients with pulmonary fibrosis and anti-MPO will develop AAV during follow-up. ANCA positivity may be detected in idiopathic or non idiopathic pulmonary fibrosis. In the absence of vasculitis, the detection of ANCA does not influence the diagnostic work-up of patients with lung fibrosis. If an Idiopathic Pulmonary Fibrosis diagnosis is considered, an anti-fibrotic therapy should be considered, according to local and international guidelines.

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Anti-parietal cell autoimmunity is associated with an accelerated decline of lung function in IPF patients

Abstract: Anti-parietal cell autoimmunity is detected in some IPF patients and is associated with an accelerated decline of lung function. Anti-parietal cell autoimmunity may promote lung fibrosis progression.

Cited by 10 publications

References 47 publications

Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS® trials

Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS® trials

A proteomics workflow reveals predictive autoantigens in idiopathic pulmonary fibrosis

Antineutrophil Cytoplasmic Antibody–Associated Lung Fibrosis

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