Jones, R.J., De Bie, E.M.D.D., Groves, E. et al. (31 more authors) (2022) Autoimmunity Is a Significant Feature of Idiopathic Pulmonary Arterial Hypertension. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 206 (1). pp. 81-93. ISSN 1073-449X
Abstract
Rationale: Autoimmunity is believed to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear whether this is causative or a bystander of disease and if it carries any prognostic or treatment significance.
Objectives: To study autoimmunity in IPAH using a large cross-sectional cohort.
Methods: Assessment of the circulating immune cell phenotype was undertaken using flow cytometry, and the profile of serum immunoglobulins was generated using a standardized multiplex array of 19 clinically validated autoantibodies in 473 cases and 946 control subjects. Additional glutathione S-transferase fusion array and ELISA data were used to identify a serum autoantibody to BMPR2 (bone morphogenetic protein receptor type 2). Clustering analyses and clinical correlations were used to determine associations between immunogenicity and clinical outcomes.
Measurements and Main Results: Flow cytometric immune profiling demonstrates that IPAH is associated with an altered humoral immune response in addition to raised IgG3. Multiplexed autoantibodies were significantly raised in IPAH, and clustering demonstrated three distinct clusters: “high autoantibody,” “low autoantibody,” and a small “intermediate” cluster exhibiting high concentrations of ribonucleic protein complex. The high-autoantibody cluster had worse hemodynamics but improved survival. A small subset of patients demonstrated immunoglobulin reactivity to BMPR2.
Conclusions: This study establishes aberrant immune regulation and presence of autoantibodies as key features in the profile of a significant proportion of patients with IPAH and is associated with clinical outcomes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | ©2022 by the American Thoracic Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | autoimmune; pulmonary arterial hypertension; BMPR2; autoantibodies; IPAH |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number BRITISH HEART FOUNDATION 33808 BRITISH HEART FOUNDATION RG68204 13/EE/0203 A092860 British Heart Foundation FS/18/52/33808 MEDICAL RESEARCH COUNCIL MR/K020919/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Dec 2022 16:30 |
Last Modified: | 24 Dec 2022 01:15 |
Status: | Published |
Publisher: | American Thoracic Society |
Refereed: | Yes |
Identification Number: | 10.1164/rccm.202108-1919OC |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:194671 |