TY - JOUR
T1 - Myositis-specific antibodies identify a distinct interstitial pneumonia with autoimmune features phenotype
AU - Graham, Julia
AU - Ventura, Iazsmin Bauer
AU - Newton, Chad A.
AU - Lee, Cathryn
AU - Boctor, Noelle
AU - Pugashetti, Janelle Vu
AU - Cutting, Claire
AU - Joerns, Elena
AU - Sandhu, Habrinder
AU - Chung, Jonathan H.
AU - Garcia, Christine K
AU - Kadoch, Michael
AU - Noth, Imre
AU - Adegunsoye, Ayodeji
AU - Strek, Mary E.
AU - Oldham, Justin M.
N1 - Funding Information:
Conflict of interest: J. Graham has nothing to disclose. I.B. Ventura has nothing to disclose. C.A. Newton has nothing to disclose. C. Lee has nothing to disclose. N. Boctor has nothing to disclose. J.V. Pugashetti has nothing to disclose. C. Cutting has nothing to disclose. E. Joerns reports grants from Pfizer, outside the submitted work. H. Sandhu has nothing to disclose. J.H. Chung has nothing to disclose. C.K. Garcia reports grants from NIH (HL093096), during the conduct of the study; grants from Astra Zeneca, outside the submitted work. M. Kadoch has nothing to disclose. I. Noth reports personal fees for research, lectures and advisory board work from BI and Genentech, grants from NIH, HLR, Stromedix and Promedior, personal fees for adjudication committee work from Gilead/Perceptive, personal fees for lectures from PILOT CME, personal fees for lectures and advisory board work from Sunovion, outside the submitted work; and has a patent TOLLIP in IPF pending, a patent Plasma proteins in IPF issued, and a patent PBMC expression signature in IPF pending. A. Adegunsoye reports lecturing for Boehringer Ingelheim, grants from Pulmonary Fibrosis Foundation and CHEST Foundation, outside the submitted work. M.E. Strek reports grants, personal fees and non-financial support from Boehringer Ingelheim, grants from Novartis, outside the submitted work. J.M. Oldham reports grants from National Institutes of Health and American College of Chest Physicians, during the conduct of the study; personal fees from Boehringer Ingelheim and Genentech, outside the submitted work.
Funding Information:
Support statement: This work was supported by the National Heart, Lung, and Blood Institute (grant: K23HL138190, K23HL146942, K23HL148498). Funding information for this article has been deposited with the Crossref Funder Registry.
Publisher Copyright:
Copyright © ERS 2020
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an antisynthetase syndrome. Whether MSAs and myositis-associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear. A multicentre, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis and non-IIM CTD-ILDs. The primary end-point assessed was 3-year transplant-free survival. 269 patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest that MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.
AB - Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an antisynthetase syndrome. Whether MSAs and myositis-associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear. A multicentre, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis and non-IIM CTD-ILDs. The primary end-point assessed was 3-year transplant-free survival. 269 patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest that MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.
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U2 - 10.1183/13993003.01205-2020
DO - 10.1183/13993003.01205-2020
M3 - Article
C2 - 32675203
AN - SCOPUS:85097512215
VL - 56
JO - Scandinavian Journal of Respiratory Diseases
JF - Scandinavian Journal of Respiratory Diseases
SN - 0903-1936
IS - 6
M1 - 2001205
ER -