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

Michel, Laurence; Farge, Dominique; Baraut, Julie; Marjanovic, Zora; Jean-Louis, Francette; Porcher, Raphaël; Grigore, E I; Deligny, C.; Romijn, Fred P.H.T.M.; Arruda, Lucas C. M.; Pelt, Johannes van; Levarht, N.; Verrecchia, Franck; Laar, Jacob M van

doi:10.1038/bmt.2016.77

Cited by 24 publications

(21 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The serum proteins correlating with the IFN and neutrophil transcript modules, as well as several Th2/M2 macrophage (PARC (CCL-18), IL-6, MCP-1 (CCL-2)) cytokines, also decreased significantly after the HSCT while there was no significant change in the CYC arm. Consistent with our findings, serum MCP-1, a prominently dysregulated cytokine in SSc,21 significantly decreased after treatment in 20 individuals with SSc undergoing HSCT in the multicentre European ASTIS study 33. Paralleling the transcript-level findings, these results confirm significant changes in the serum protein signatures of SSc after HSCT.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2019

View full text Add to dashboard Cite

ObjectiveIn 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.MethodsGlobal 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.ResultsAt 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.ConclusionHSCT contrary to conventional treatment leads to a significant ‘correction’ in disease-related molecular signatures.

show abstract

Section: Discussionsupporting

confidence: 90%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Thereafter, Tsukamoto et al found persistent inversion of the Th2/Th1 ratio in eleven SSc patients until 3 years post-aHSCT [12]. In a pilot study, we reported restoration of Tregs and their suppressive function 2 years after aHSCT in seven SSc patients compared to controls [13], and partial fall of the pre-transplant increase in pro-fibrotic and Th2-cytokines serum levels [14]. Several questions remain, such as which of the post-transplant IR mechanisms are most relevant to warrant prolonged remission and what is the duration of the immunological transplant-induced effects?…”

Section: Introductionmentioning

confidence: 93%

Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients

et al. 2017

View full text Add to dashboard Cite

The determinants of clinical responses after autologous hematopoietic stem cell transplantation (aHSCT) in systemic sclerosis (SSc) are still unraveled. We analyzed long-term immune reconstitution (IR) and T cell receptor (TCR) repertoire diversity in 10 SSc patients, with at least 6 years simultaneous clinical and immunological follow-up after aHSCT. Patients were retrospectively classified as long-term responders (A, n = 5) or non-responders (B, n = 5), using modified Rodnan’s skin score (mRSS) and forced vital capacity (FVC%). All patients had similar severe SSc before aHSCT. Number of reinjected CD34+ cells was higher in group B versus A (P = 0.02). Long-term mRSS fall >25% was more pronounced in group A (P = 0.004), the only to improve long-term FVC% >10% (P = 0.026). There was an overall trend toward increased of T cell reconstitution in group B versus A. B cells had a positive linear regression slope in group A (LRS = 11.1) and negative in group B (LRS = −11.6). TCR repertoire was disturbed before aHSCT and the percentage of polyclonal families significantly increased at long-term (P = 0.046), with no difference between groups. Despite improved skin score after aHSCT in all SSc patients, pretransplant B cell clonal expansion and faster post-transplant T cell IR in long-term non-responder/relapsing patients call for new therapeutic protocols guided by IR analysis to improve their outcome.

show abstract

“…The first study analyzed the serum levels of inflammatory cytokines (IL-2, IL-6, IL-8, and IFN-γ), pro-fibrotic molecules (TGF-β, IL-4, and PDGF), pro-angiogenic factors (VEGF and PDGF), endothelial markers (E-selectin and P-selectin) and MCP-1 chemokine before and up to 4 years after HSCT in 20 SSc patients. Even though a decrease in IL-2 and IL-8 levels, along with a slight but significant decrease in TGF-ß levels after 6 months has been demonstrated, these fluctuations did not reflect the skin score improvement after AHSCT ( 53 ).…”

Section: Immunologic Mechanisms Of Ahsctmentioning

confidence: 98%

Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis

et al. 2018

View full text Add to dashboard Cite

Systemic Sclerosis (SSc) is a complex autoimmune disease, characterized by high mortality and morbidity. The heterogeneity in terms of extent, severity, and rate of progression of skin and internal organ involvement gives rise to many difficulties in finding the optimal therapeutic interventions for SSc and, to date, no disease-modifying agents are available. In this scenario, it is not surprising that SSc was one of the first autoimmune diseases challenged with high-dose immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (AHSCT). In the last decades, AHSCT has emerged as a treatment option for refractory SSc through a reduction of the aberrant immune cells, followed by re-constitution of a new, self-tolerant immune system. After several case series and pilot studies, more recently three randomized controlled trials have shown a benefit in skin involvement, organ functions and quality of life measures in AHSCT compared to monthly cyclophosphamide. In addition, although AHSCT presents a certain risk of mortality, it has been shown that the overall survival is better, compared to the cyclophosphamide group. Current evidence suggests that SSc patients who are most likely to benefit from AHSCT are early, active, with rapidly progressing diffuse skin disease, and mild involvement of internal organs. As the studies have progressed, it has become evident the need for a more rigorous patient selection, the optimization of transplant and post-transplant procedures, and the intervention of multidisciplinary teams of specialists to increase the safety and efficacy of AHSCT in SSc.

show abstract

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

Cited by 24 publications

References 14 publications

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

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

Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients

Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis

Contact Info

Product

Resources

About