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Myeloablation followed by autologous stem cell transplantation normalises systemic sclerosis molecular signatures
  1. Shervin Assassi1,
  2. Xuan Wang2,
  3. Guocai Chen3,
  4. Ellen Goldmuntz4,
  5. Lynette Keyes-Elstein5,
  6. Jun Ying1,
  7. Paul K Wallace6,
  8. Jacob Turner7,
  9. W Jim Zheng3,
  10. Virginia Pascual8,
  11. John Varga9,
  12. Monique E Hinchcliff10,
  13. Chiara Bellocchi1,
  14. Peter McSweeney11,
  15. Daniel E Furst12,13,
  16. Richard A Nash11,
  17. Leslie J Crofford14,
  18. Beverly Welch4,
  19. Ashley Pinckney15,
  20. Maureen D Mayes1,
  21. Keith M Sullivan16
  1. 1 Rheumatology, University of Texas Health Science Center at Houston, Houston, Texas, USA
  2. 2 Biostatistics, Baylor Institute for Immunology Research, Dallas, Texas, USA
  3. 3 School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, Texas, USA
  4. 4 Allergy, Immunology, and Transplantation, NIH/NIAID, Bethesda, Maryland, USA
  5. 5 Infectious and autoimmune diseases, Rho, Chapel Hill, North Carolina, USA
  6. 6 Flow and Image Cytometry, Roswell Park Cancer Institute, Buffalo, New York, USA
  7. 7 Mathematics and Statistics, Stephen F Austin State University, Nacogdoches, Texas, USA
  8. 8 Pediatrics, Weill Cornell Medical College, New York, New York, USA
  9. 9 Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  10. 10 Rheumatology, Yale University, New Haven, Connecticut, USA
  11. 11 Rocky Mountain Blood and Marrow Transplant Program, Colorado Blood Cancer Institute, Denver, Colorado, USA
  12. 12 Rheumatology, University of California Los Angeles, Los Angeles, California, USA
  13. 13 Rheumatology, University of Washington, Seattle, Washington, USA
  14. 14 Rheumatology, Vanderbilt University, Nashville, Tennessee, USA
  15. 15 Rho Federal Systems Division, Chapel Hill, North Carolina, USA
  16. 16 Hematologic Malignancy and Cellular Therapy, Duke University, Durham, North Carolina, USA
  1. Correspondence to Dr Shervin Assassi, Rheumatology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; shervin.assassi{at}


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.

  • systemic sclerosis
  • hematopoietic stem cell transplantation
  • cyclophosphamide
  • interferon signature
  • neutrophil

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  • Handling editor Josef S Smolen

  • Contributors Conception and design of the study: SA, EG, LK-E, PM, DEF, RAN, LJC, MDM and KMS. Acquisition of the study data:SA, EG, LK-E, JV, MEH, PM, DEF, RAN, LJC, BW, AP, MDM and KMS. Analysis or interpretation of the study data:SA, XW, GC, EG, LK-E, JY, PKW, JT, WJZ, VP, CB, DEF, AP, MDM and KMS. All authors have contributed to drafting and revising the manuscript and have approved its final version.

  • Funding The SCOT study was supported by awards from the NIAID, NIH to Duke University, the study contract holder (N01-AI05419 and HHSN 272201100025C). The study was also supported by grants from Karen Brown Scleroderma Foundation, NIH NIAMS (P30-AR061271), NIH R01AR073284, NIH UL1-TR000371 and Department of Defense (W81XWH-16-1-0296).

  • Disclaimer The gene expression data and related de-identified clinical information are deposited on Gene Expression Omnibus (GEO) database - Accession number: GSE130953.

  • Competing interests SA reports grants from National Institute of Health, grants from Karen Brown Scleroderma Foundation, grants from Department of Defense, during the conduct of the study; grants and personal fees from Boehringer Ingelheim, personal fees from Integrity Continuing Education, personal fees from Medscape, outside the submitted work. MDM reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Galapagos NV (Pharma), personal fees from Medtelligence, personal fees from Actelion Pharma, personal fees from Astellas, personal fees from Mitsubishi-Tanabe, grants from Bayer, grants from Reata, grants from Sanofi, grants from Corbus, grants from Eicos/ Sciences, outside the submitted work. KMS reports grants from National Institutes of Health, NIAID, during the conduct of the study; personal fees from GlaxoSmith/Kline, grants from Astra Zeneca, grants from Takeda Millennium, personal fees from Magenta, personal fees from Aerotek, personal fees from Kiadis Pharma, from Genentech Roche, outside the submitted work.

  • Patient consent for publication Not required.

  • Ethics approval The SCOT study protocol was approved by the local Institutional Review Board of the participating institutions.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository.

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