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Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis

Donahoe, M and Valentine, VG and Chien, N and Gibson, KF and Raval, JS and Saul, M and Xue, J and Zhang, Y and Duncan, SR (2015) Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis. PLoS ONE, 10 (6).

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Abstract

© 2015 Donahoe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Severe acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are medically untreatable and often fatal within days. Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. We conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit AE-IPF patients. Methods: Eleven (11) critically-ill AE-IPF patients with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Plasma anti-epithelial (HEp-2) autoantibodies and matrix metalloproteinase-7 (MMP7) were evaluated by indirect immunofluorescence and ELISA, respectively. Outcomes among the trial subjects were compared to those of 20 historical control AE-IPF patients treated with conventional glucocorticoid therapy prior to this experimental trial. Results: Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one (5%) historical control. Two of the three trial subjects who relapsed after only five TPE responded again with additional TPE. The three latest subjects who responded to an augmented regimen of nine TPE plus rituximab plus IVIG have had sustained responses without relapses after 96-to-237 days. Anti-HEp-2 autoantibodies were present in trial subjects prior to therapy, and were reduced by TPE among those who responded to treatment. Conversely, plasma MMP7 levels were not systematically affected by therapy nor correlated with clinical responses. One-year survival of trial subjects was 46+15% vs. 0% among historical controls. No serious adverse events were attributable to the experimental medications. Conclusion: This pilot trial indicates specific treatments that reduce autoantibodies might benefit some severely-ill AE-IPF patients. These findings have potential implications regarding mechanisms of IPF progression, and justify considerations for incremental trials of autoantibody-targeted therapies in AE-IPF patients. Trial Registration: ClinicalTrials.gov NCT01266317.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Donahoe, Mmpd@pitt.eduMPD
Valentine, VG
Chien, Nnnc3@pitt.eduNNC3
Gibson, KFkfg@pitt.eduKFG
Raval, JS
Saul, Mmis18@pitt.eduMIS180000-0002-6712-5102
Xue, Jjix28@pitt.eduJIX28
Zhang, Y
Duncan, SR
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorMaher, Toby M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 17 June 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0127771
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Biomedical Informatics
School of Medicine > Medicine
Refereed: Yes
Date Deposited: 23 Aug 2016 14:20
Last Modified: 05 Dec 2018 17:55
URI: http://d-scholarship.pitt.edu/id/eprint/28467

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