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@article{Jones:2022:10.1164/rccm.202108-1919OC,
author = {Jones, RJ and De, Bie EMDD and Groves, E and Zalewska, KI and Swietlik, EM and Treacy, CM and Martin, JM and Polwarth, G and Li, W and Guo, J and Baxendale, HE and Coleman, S and Savinykh, N and Coghlan, JG and Corris, PA and Howard, LS and Johnson, MK and Church, C and Kiely, DG and Lawrie, A and Lordan, JL and Mackenzie, Ross RV and Pepke, Zaba J and Wilkins, MR and Wort, SJ and Fiorillo, E and Orrù, V and Cucca, F and Rhodes, CJ and Gräf, S and Morrell, NW and McKinney, EF and Wallace, C and Toshner, M and UK, National PAH Cohort Study Consortium},
doi = {10.1164/rccm.202108-1919OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {81--93},
title = {Autoimmunity is a significant feature of idiopathic pulmonary arterial hypertension.},
url = {http://dx.doi.org/10.1164/rccm.202108-1919OC},
volume = {206},
year = {2022}
}

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TY  - JOUR
AB  - RATIONALE: Autoimmunity is thought to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear if this is causative or a bystander of disease and if it carries any prognostic or treatment significance. OBJECTIVE: 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 standardised multiplex array of 19 clinically validated autoantibodies in 473 cases and 946 controls. Additional GST-fusion array and ELISA data were used to identify a serum autoantibody to BMPR2. Clustering analyses and clinical correlations were employed to determine associations between immunogenicity and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Flow cytometric immune profiling demonstrates 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 levels of RNP-complex. The high autoantibody cluster had worse haemodynamics 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 a key feature in the profile of a significant proportion of IPAH patients and is associated with clinical outcomes. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
AU  - Jones,RJ
AU  - De,Bie EMDD
AU  - Groves,E
AU  - Zalewska,KI
AU  - Swietlik,EM
AU  - Treacy,CM
AU  - Martin,JM
AU  - Polwarth,G
AU  - Li,W
AU  - Guo,J
AU  - Baxendale,HE
AU  - Coleman,S
AU  - Savinykh,N
AU  - Coghlan,JG
AU  - Corris,PA
AU  - Howard,LS
AU  - Johnson,MK
AU  - Church,C
AU  - Kiely,DG
AU  - Lawrie,A
AU  - Lordan,JL
AU  - Mackenzie,Ross RV
AU  - Pepke,Zaba J
AU  - Wilkins,MR
AU  - Wort,SJ
AU  - Fiorillo,E
AU  - Orrù,V
AU  - Cucca,F
AU  - Rhodes,CJ
AU  - Gräf,S
AU  - Morrell,NW
AU  - McKinney,EF
AU  - Wallace,C
AU  - Toshner,M
AU  - UK,National PAH Cohort Study Consortium
DO  - 10.1164/rccm.202108-1919OC
EP  - 93
PY  - 2022///
SN  - 1073-449X
SP  - 81
TI  - Autoimmunity is a significant feature of idiopathic pulmonary arterial hypertension.
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.202108-1919OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35316153
UR  - https://www.atsjournals.org/doi/10.1164/rccm.202108-1919OC
UR  - http://hdl.handle.net/10044/1/96049
VL  - 206
ER  -

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