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

TitleMyeloablation followed by autologous stem cell transplantation normalises systemic sclerosis molecular signatures.
Publication TypeJournal Article
Year of Publication2019
AuthorsAssassi S, Wang X, Chen G, Goldmuntz E, Keyes-Elstein L, Ying J, Wallace PK, Turner J, W Zheng J, Pascual V, Varga J, Hinchcliff ME, Bellocchi C, McSweeney P, Furst DE, Nash RA, Crofford LJ, Welch B, Pinckney A, Mayes MD, Sullivan KM
JournalAnn Rheum Dis
Volume78
Issue10
Pagination1371-1378
Date Published2019 10
ISSN1468-2060
KeywordsAdult, Cyclophosphamide, Down-Regulation, Female, Hematopoietic Stem Cell Transplantation, Humans, Interferons, Male, Middle Aged, Multilevel Analysis, Myeloablative Agonists, Neutrophils, Randomized Controlled Trials as Topic, Scleroderma, Systemic, Transcriptome, Transplantation Conditioning, Transplantation, Autologous, Treatment Outcome, Up-Regulation
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.

DOI10.1136/annrheumdis-2019-215770
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https://www.ncbi.nlm.nih.gov/pubmed/31391177?dopt=Abstract

Alternate JournalAnn. Rheum. Dis.
PubMed ID31391177
PubMed Central IDPMC7167108
Grant ListHHSN272201100025C / AI / NIAID NIH HHS / United States
N01AI05419 / AI / NIAID NIH HHS / United States
UL1 TR003167 / TR / NCATS NIH HHS / United States
KL2 TR003168 / TR / NCATS NIH HHS / United States
P30 AR061271 / AR / NIAMS NIH HHS / United States
R01 AR073284 / AR / NIAMS NIH HHS / United States
UL1 TR000371 / TR / NCATS NIH HHS / United States

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