RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

The RA-MAP Consortium

doi:10.1038/s41597-022-01264-y

RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

The RA-MAP Consortium

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.

Original language	English
Article number	196
Number of pages	13
Journal	Scientific Data
Volume	9
Issue number	1
Early online date	9 May 2022
DOIs	https://doi.org/10.1038/s41597-022-01264-y
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
The RA-MAP Consortium is a UK industry-academic precision medicine partnership funded by the Medical Research Council and the Association of the British Pharmaceutical Industry (ABPI). RA-MAP’s goals are to investigate clinical and biological predictors of disease outcome and treatment response in RA, using deep clinical and multi-omic phenotyping (Fig. ). The study is in part motivated to inform the study design and analysis of future studies of blood and immune cell subsets in RA and other IMIDs. RA-MAP patients follow the UK-NHS standard of care, with first-line treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), such as methotrexate, which have slow onset of action. In the case of non-responders to csDMARDs, prolonged periods of uncontrolled disease activity can lead to joint damage and disability. Thus, RA-MAP seeks to address a major unmet need to identify patient-level predictors of response in order to identify patients with a greater or lesser chance of clinically responding to csDMARD treatment. Such information could guide treatment choices, possibly supporting fast-track biologic therapy, leading to improved long-term outcomes for patients, and saving time and money in achieving sustained disease control and improving the efficiency of clinical trials.

The programme of research described in this article is funded by the Medical Research Council, UK (An Immunological Toolkit for Clinical Application, grant number G1001518 and Towards a cure for early rheumatoid arthritis, grant number G1001516). The RA-MAP Consortium would particularly like to thank members of the MRC Immunity and Inflammation Stratified Medicine Steering Group and Officers of the Medical Research Council who have supported the work of RA-MAP from the outset. In addition, the RA-MAP team acknowledges the exceptional contributions and talents of Christopher John (1986–2020), Meilien Ho (1960–2016) and Sally Hollis (1967–2019). This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure supported by the Medical Research Council [grant number MR/L016311/1]. SV is supported by Versus Arthritis (grant numbers 20385, 20380) and the NIHR Manchester Biomedical Research Centre, UK. JDI is a National Institute for Health Research (NIHR) Senior Investigator and his work is supported by the Research into Inflammatory Arthritis Centre Versus Arthritis and the NIHR Newcastle Biomedical Research Centre in Ageing and Long-term Conditions. The views expressed are those of the author(s) and not necessarily those of the National Institute for Health Research NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

Statistics and Probability
Information Systems
Education
Computer Science Applications
Statistics, Probability and Uncertainty
Library and Information Sciences

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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IsaacsJ2022RAMAPFinal published version, 2.42 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

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title = "RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients",

abstract = "Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.",

author = "{The RA-MAP Consortium} and Isaacs, {John D.} and Sarah Brockbank and Pedersen, {Ayako Wakatsuki} and Catharien Hilkens and Amy Anderson and Philip Stocks and Dennis Lendrem and Jessica Tarn and Smith, {Graham R.} and Ben Allen and John Casement and Julie Diboll and Rachel Harry and Cooles, {Faye A. H.} and Cope, {Andrew P.} and Gemma Simpson and Ruth Toward and Hayley Noble and Angela Parke and Wing Wu and Fiona Clarke and David Scott and Scott, {Ian C.} and James Galloway and Heidi Lempp and Fowzia Ibrahim and Samana Schwank and Gemma Molyneux and Tomi Lazarov and Frederic Geissmann and Goodyear, {Carl S.} and McInnes, {Iain B} and Iona Donnelly and Ashley Gilmour and Virlan, {Aysin Tulunay} and Duncan Porter and Frederique Ponchel and Paul Emery and Jehan El-Jawhari and Rekha Parmar and Mcdermott, {Michael F.} and Fisher, {Benjamin A.} and Young, {Steve P.} and Philip Jones and Karim Raza and Andrew Filer and Constantino Pitzalis and Barnes, {Michael R.} and Watson, {David S.} and Buckley, {Christopher D.}",

note = "Funding Information: The RA-MAP Consortium is a UK industry-academic precision medicine partnership funded by the Medical Research Council and the Association of the British Pharmaceutical Industry (ABPI). RA-MAP{\textquoteright}s goals are to investigate clinical and biological predictors of disease outcome and treatment response in RA, using deep clinical and multi-omic phenotyping (Fig. ). The study is in part motivated to inform the study design and analysis of future studies of blood and immune cell subsets in RA and other IMIDs. RA-MAP patients follow the UK-NHS standard of care, with first-line treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), such as methotrexate, which have slow onset of action. In the case of non-responders to csDMARDs, prolonged periods of uncontrolled disease activity can lead to joint damage and disability. Thus, RA-MAP seeks to address a major unmet need to identify patient-level predictors of response in order to identify patients with a greater or lesser chance of clinically responding to csDMARD treatment. Such information could guide treatment choices, possibly supporting fast-track biologic therapy, leading to improved long-term outcomes for patients, and saving time and money in achieving sustained disease control and improving the efficiency of clinical trials. The programme of research described in this article is funded by the Medical Research Council, UK (An Immunological Toolkit for Clinical Application, grant number G1001518 and Towards a cure for early rheumatoid arthritis, grant number G1001516). The RA-MAP Consortium would particularly like to thank members of the MRC Immunity and Inflammation Stratified Medicine Steering Group and Officers of the Medical Research Council who have supported the work of RA-MAP from the outset. In addition, the RA-MAP team acknowledges the exceptional contributions and talents of Christopher John (1986–2020), Meilien Ho (1960–2016) and Sally Hollis (1967–2019). This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure supported by the Medical Research Council [grant number MR/L016311/1]. SV is supported by Versus Arthritis (grant numbers 20385, 20380) and the NIHR Manchester Biomedical Research Centre, UK. JDI is a National Institute for Health Research (NIHR) Senior Investigator and his work is supported by the Research into Inflammatory Arthritis Centre Versus Arthritis and the NIHR Newcastle Biomedical Research Centre in Ageing and Long-term Conditions. The views expressed are those of the author(s) and not necessarily those of the National Institute for Health Research NIHR or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41597-022-01264-y",

language = "English",

volume = "9",

journal = "Scientific Data",

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T1 - RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

AU - The RA-MAP Consortium

AU - Isaacs, John D.

AU - Brockbank, Sarah

AU - Pedersen, Ayako Wakatsuki

AU - Hilkens, Catharien

AU - Anderson, Amy

AU - Stocks, Philip

AU - Lendrem, Dennis

AU - Tarn, Jessica

AU - Smith, Graham R.

AU - Allen, Ben

AU - Casement, John

AU - Diboll, Julie

AU - Harry, Rachel

AU - Cooles, Faye A. H.

AU - Cope, Andrew P.

AU - Simpson, Gemma

AU - Toward, Ruth

AU - Noble, Hayley

AU - Parke, Angela

AU - Wu, Wing

AU - Clarke, Fiona

AU - Scott, David

AU - Scott, Ian C.

AU - Galloway, James

AU - Lempp, Heidi

AU - Ibrahim, Fowzia

AU - Schwank, Samana

AU - Molyneux, Gemma

AU - Lazarov, Tomi

AU - Geissmann, Frederic

AU - Goodyear, Carl S.

AU - McInnes, Iain B

AU - Donnelly, Iona

AU - Gilmour, Ashley

AU - Virlan, Aysin Tulunay

AU - Porter, Duncan

AU - Ponchel, Frederique

AU - Emery, Paul

AU - El-Jawhari, Jehan

AU - Parmar, Rekha

AU - Mcdermott, Michael F.

AU - Fisher, Benjamin A.

AU - Young, Steve P.

AU - Jones, Philip

AU - Raza, Karim

AU - Filer, Andrew

AU - Pitzalis, Constantino

AU - Barnes, Michael R.

AU - Watson, David S.

AU - Buckley, Christopher D.

N1 - Funding Information: The RA-MAP Consortium is a UK industry-academic precision medicine partnership funded by the Medical Research Council and the Association of the British Pharmaceutical Industry (ABPI). RA-MAP’s goals are to investigate clinical and biological predictors of disease outcome and treatment response in RA, using deep clinical and multi-omic phenotyping (Fig. ). The study is in part motivated to inform the study design and analysis of future studies of blood and immune cell subsets in RA and other IMIDs. RA-MAP patients follow the UK-NHS standard of care, with first-line treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), such as methotrexate, which have slow onset of action. In the case of non-responders to csDMARDs, prolonged periods of uncontrolled disease activity can lead to joint damage and disability. Thus, RA-MAP seeks to address a major unmet need to identify patient-level predictors of response in order to identify patients with a greater or lesser chance of clinically responding to csDMARD treatment. Such information could guide treatment choices, possibly supporting fast-track biologic therapy, leading to improved long-term outcomes for patients, and saving time and money in achieving sustained disease control and improving the efficiency of clinical trials. The programme of research described in this article is funded by the Medical Research Council, UK (An Immunological Toolkit for Clinical Application, grant number G1001518 and Towards a cure for early rheumatoid arthritis, grant number G1001516). The RA-MAP Consortium would particularly like to thank members of the MRC Immunity and Inflammation Stratified Medicine Steering Group and Officers of the Medical Research Council who have supported the work of RA-MAP from the outset. In addition, the RA-MAP team acknowledges the exceptional contributions and talents of Christopher John (1986–2020), Meilien Ho (1960–2016) and Sally Hollis (1967–2019). This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure supported by the Medical Research Council [grant number MR/L016311/1]. SV is supported by Versus Arthritis (grant numbers 20385, 20380) and the NIHR Manchester Biomedical Research Centre, UK. JDI is a National Institute for Health Research (NIHR) Senior Investigator and his work is supported by the Research into Inflammatory Arthritis Centre Versus Arthritis and the NIHR Newcastle Biomedical Research Centre in Ageing and Long-term Conditions. The views expressed are those of the author(s) and not necessarily those of the National Institute for Health Research NIHR or the Department of Health and Social Care. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.

AB - Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.

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DO - 10.1038/s41597-022-01264-y

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SN - 2052-4463

VL - 9

JO - Scientific Data

JF - Scientific Data

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RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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