Literature DB >> 31391177

Myeloablation followed by autologous stem cell transplantation normalises systemic sclerosis molecular signatures.

Shervin Assassi1, Xuan Wang2, Guocai Chen3, Ellen Goldmuntz4, Lynette Keyes-Elstein5, Jun Ying6, Paul K Wallace7, Jacob Turner8, W Jim Zheng3, Virginia Pascual9, John Varga10, Monique E Hinchcliff11, Chiara Bellocchi6, Peter McSweeney12, Daniel E Furst13,14, Richard A Nash12, Leslie J Crofford15, Beverly Welch4, Ashley Pinckney16, Maureen D Mayes6, Keith M Sullivan17.   

Abstract

OBJECTIVE: In the randomised scleroderma: Cyclophosphamide Or Transplantation (SCOT trial) (NCT00114530), myeloablation, followed by haematopoietic stem cell transplantation (HSCT), led to improved clinical outcomes compared with monthly cyclophosphamide (CYC) treatment in systemic sclerosis (SSc). Herein, the study aimed to determine global molecular changes at the whole blood transcript and serum protein levels ensuing from HSCT in comparison to intravenous monthly CYC in 62 participants enrolled in the SCOT study.
METHODS: Global transcript studies were performed at pretreatment baseline, 8 months and 26 months postrandomisation using Illumina HT-12 arrays. Levels of 102 proteins were measured in the concomitantly collected serum samples.
RESULTS: At the baseline visit, interferon (IFN) and neutrophil transcript modules were upregulated and the cytotoxic/NK module was downregulated in SSc compared with unaffected controls. A paired comparison of the 26 months to the baseline samples revealed a significant decrease of the IFN and neutrophil modules and an increase in the cytotoxic/NK module in the HSCT arm while there was no significant change in the CYC control arm. Also, a composite score of correlating serum proteins with IFN and neutrophil transcript modules, as well as a multilevel analysis showed significant changes in SSc molecular signatures after HSCT while similar changes were not observed in the CYC arm. Lastly, a decline in the IFN and neutrophil modules was associated with an improvement in pulmonary forced vital capacity and an increase in the cytotoxic/NK module correlated with improvement in skin score.
CONCLUSION: HSCT contrary to conventional treatment leads to a significant 'correction' in disease-related molecular signatures. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Entities:  

Keywords:  cyclophosphamide; hematopoietic stem cell transplantation; interferon signature; neutrophil; systemic sclerosis

Mesh：

Substances：

Year:  2019        PMID： 31391177      PMCID： PMC7167108          DOI： 10.1136/annrheumdis-2019-215770

Source DB:  PubMed          Journal:  Ann Rheum Dis        ISSN： 0003-4967            Impact factor:   19.103


  38 in total

1.  Stabilization of mRNA expression in whole blood samples.

Authors:  Lynne Rainen; Uwe Oelmueller; Stewart Jurgensen; Ralf Wyrich; Cynthia Ballas; Jim Schram; Chris Herdman; Danute Bankaitis-Davis; Nancy Nicholls; David Trollinger; Victor Tryon
Journal:  Clin Chem       Date:  2002-11       Impact factor: 8.327

2.  Systemic sclerosis and lupus: points in an interferon-mediated continuum.

Authors:  Shervin Assassi; Maureen D Mayes; Frank C Arnett; Pravitt Gourh; Sandeep K Agarwal; Terry A McNearney; Damien Chaussabel; Nancy Oommen; Michael Fischbach; Kairav R Shah; Julio Charles; Virginia Pascual; John D Reveille; Filemon K Tan
Journal:  Arthritis Rheum       Date:  2010-02

3.  Evolution of serum cytokine profile after hematopoietic stem cell transplantation in systemic sclerosis patients.

Authors:  L Michel; D Farge; J Baraut; Z Marjanovic; F Jean-Louis; R Porcher; E I Grigore; C Deligny; F Romijn; L C M Arruda; J van Pelt; N Levarht; F Verrecchia; J M van Laar
Journal:  Bone Marrow Transplant       Date:  2016-04-04       Impact factor: 5.483

4.  Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.

Authors:  Keith M Sullivan; Ellen A Goldmuntz; Lynette Keyes-Elstein; Peter A McSweeney; Ashley Pinckney; Beverly Welch; Maureen D Mayes; Richard A Nash; Leslie J Crofford; Barry Eggleston; Sharon Castina; Linda M Griffith; Julia S Goldstein; Dennis Wallace; Oana Craciunescu; Dinesh Khanna; Rodney J Folz; Jonathan Goldin; E William St Clair; James R Seibold; Kristine Phillips; Shin Mineishi; Robert W Simms; Karen Ballen; Mark H Wener; George E Georges; Shelly Heimfeld; Chitra Hosing; Stephen Forman; Suzanne Kafaja; Richard M Silver; Leroy Griffing; Jan Storek; Sharon LeClercq; Richard Brasington; Mary E Csuka; Christopher Bredeson; Carolyn Keever-Taylor; Robyn T Domsic; M Bashar Kahaleh; Thomas Medsger; Daniel E Furst
Journal:  N Engl J Med       Date:  2018-01-04       Impact factor: 91.245

5.  Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial.

Authors:  Richard K Burt; Sanjiv J Shah; Karin Dill; Thomas Grant; Mihai Gheorghiade; James Schroeder; Robert Craig; Ikuo Hirano; Karin Marshall; Eric Ruderman; Borko Jovanovic; Francesca Milanetti; Sandeep Jain; Kristin Boyce; Amy Morgan; James Carr; Walter Barr
Journal:  Lancet       Date:  2011-07-21       Impact factor: 79.321

6.  High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis.

Authors:  Anna-Maria Hoffmann-Vold; Anders Heiervang Tennøe; Torhild Garen; Øyvind Midtvedt; Aurelija Abraityte; Trond Mogens Aaløkken; May Britt Lund; Cathrine Brunborg; Pål Aukrust; Thor Ueland; Øyvind Molberg
Journal:  Chest       Date:  2016-03-18       Impact factor: 9.410

7.  Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus.

Authors:  W J McCune; J Golbus; W Zeldes; P Bohlke; R Dunne; D A Fox
Journal:  N Engl J Med       Date:  1988-06-02       Impact factor: 91.245

8.  Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells.

Authors:  R Manetti; P Parronchi; M G Giudizi; M P Piccinni; E Maggi; G Trinchieri; S Romagnani
Journal:  J Exp Med       Date:  1993-04-01       Impact factor: 14.307

9.  Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern.

Authors:  Michael Gernert; Hans-Peter Tony; Eva Christina Schwaneck; Ottar Gadeholt; Marc Schmalzing
Journal:  Arthritis Res Ther       Date:  2019-04-29       Impact factor: 5.156

10.  Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

Authors:  Jacob M van Laar; Dominique Farge; Jacob K Sont; Kamran Naraghi; Zora Marjanovic; Jérôme Larghero; Annemie J Schuerwegh; Erik W A Marijt; Madelon C Vonk; Anton V Schattenberg; Marco Matucci-Cerinic; Alexandre E Voskuyl; Arjan A van de Loosdrecht; Thomas Daikeler; Ina Kötter; Marc Schmalzing; Thierry Martin; Bruno Lioure; Stefan M Weiner; Alexander Kreuter; Christophe Deligny; Jean-Marc Durand; Paul Emery; Klaus P Machold; Francoise Sarrot-Reynauld; Klaus Warnatz; Daniel F P Adoue; Joël Constans; Hans-Peter Tony; Nicoletta Del Papa; Athanasios Fassas; Andrea Himsel; David Launay; Andrea Lo Monaco; Pierre Philippe; Isabelle Quéré; Éric Rich; Rene Westhovens; Bridget Griffiths; Riccardo Saccardi; Frank H van den Hoogen; Willem E Fibbe; Gérard Socié; Alois Gratwohl; Alan Tyndall
Journal:  JAMA       Date:  2014-06-25       Impact factor: 56.272
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  15 in total

1.  Clinical and Molecular Findings after Autologous Stem Cell Transplantation or Cyclophosphamide for Scleroderma: Handling Missing Longitudinal Data.

Authors:  Lynette Keyes-Elstein; Ashley Pinckney; Ellen Goldmuntz; Beverly Welch; Jennifer M Franks; Viktor Martyanov; Tammara A Wood; Leslie Crofford; Maureen Mayes; Peter McSweeney; Richard Nash; George Georges; M E Csuka; Robert Simms; Daniel Furst; Dinesh Khanna; E William St Clair; Michael L Whitfield; Keith M Sullivan
Journal:  Arthritis Care Res (Hoboken)       Date:  2021-09-17       Impact factor: 4.794

Review 2.  Assessment of disease outcome measures in systemic sclerosis.

Authors:  Robert Lafyatis; Eleanor Valenzi
Journal:  Nat Rev Rheumatol       Date:  2022-07-20       Impact factor: 32.286

Review 3.  Stem cell transplantation for systemic sclerosis.

Authors:  Sebastian Bruera; Harish Sidanmat; Donald A Molony; Maureen D Mayes; Maria E Suarez-Almazor; Kate Krause; Maria Angeles Lopez-Olivo
Journal:  Cochrane Database Syst Rev       Date:  2022-07-29

4.  Dysregulation of Type 1 Interferon Signaling in Systemic Sclerosis: a Promising Therapeutic Target?

Authors:  Minghua Wu; Shervin Assassi
Journal:  Curr Treatm Opt Rheumatol       Date:  2021-10-19

5.  Blood neutrophil count and neutrophil-to-lymphocyte ratio predict disease progression and mortality in two independent systemic sclerosis cohorts.

Authors:  Nancy Wareing; Vishnu Mohan; Rana Taherian; Elizabeth R Volkmann; Marka A Lyons; Holly Wilhalme; Michael D Roth; Rosa M Estrada-Y-Martin; Brian Skaug; Maureen D Mayes; Donald P Tashkin; Shervin Assassi
Journal:  Arthritis Care Res (Hoboken)       Date:  2022-03-14       Impact factor: 5.178

6.  Large-Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis.

Authors:  Chiara Bellocchi; Jun Ying; Ellen A Goldmuntz; Lynette Keyes-Elstein; John Varga; Monique E Hinchcliff; Marka A Lyons; Peter McSweeney; Daniel E Furst; Richard Nash; Leslie J Crofford; Beverly Welch; Jonathan G Goldin; Ashley Pinckney; Maureen D Mayes; Keith M Sullivan; Shervin Assassi
Journal:  Arthritis Rheumatol       Date:  2021-02-28       Impact factor: 10.995

7.  Predictive Significance of Serum Interferon-Inducible Protein Score for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease.

Authors:  Shervin Assassi; Ning Li; Elizabeth R Volkmann; Maureen D Mayes; Dennis Rünger; Jun Ying; Michael D Roth; Monique Hinchcliff; Dinesh Khanna; Tracy Frech; Philip J Clements; Daniel E Furst; Jonathan Goldin; Elana J Bernstein; Flavia V Castelino; Robyn T Domsic; Jessica K Gordon; Faye N Hant; Ami A Shah; Victoria K Shanmugam; Virginia D Steen; Robert M Elashoff; Donald P Tashkin
Journal:  Arthritis Rheumatol       Date:  2021-04-20       Impact factor: 15.483

Review 8.  The role of innate immune cells in systemic sclerosis in the context of autologous hematopoietic stem cell transplantation.

Authors:  N H Servaas; J Spierings; A Pandit; J M van Laar
Journal:  Clin Exp Immunol       Date:  2020-02-17       Impact factor: 4.330

9.  Interstitial Lung Disease in Systemic Sclerosis: Focus on Early Detection and Intervention.

Authors:  Aryeh Fischer; Nina M Patel; Elizabeth R Volkmann
Journal:  Open Access Rheumatol       Date:  2019-12-09

Review 10.  Systemic sclerosis (scleroderma): remaining challenges.

Authors:  Mary Karin Connolly
Journal:  Ann Transl Med       Date:  2021-03
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