Immunomodulatory effects of extracorporeal photochemotherapy in systemic sclerosis

Papp, Gábor; Horváth, Ildikó; Baráth, Sándor; Gyimesi, Edit; Végh, Judit; Szodoray, Péter; Zeher, Margit

doi:10.1016/j.clim.2011.09.014

Cited by 47 publications

(41 citation statements)

References 21 publications

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“…[72][73][74][75][76][77] Data suggest that ECP facilitates a milieu of transplantation tolerance, decreasing effector lymphocyte populations, enriching for regulatory lymphocytes and suppressor antigen-presenting cells. [78][79][80] One study showed benefit for BOS patients with etanercept, which inhibits the tumor necrosis factor receptor, and diminishes ensuing inflammation. 81 Although there are exciting translational data emerging for the role of B cells in BOS, to date, data has not shown efficacy for treatment with rituximab, nor have I witnessed benefit with this agent.…”

Section: 305253mentioning

confidence: 99%

How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Williams

2017

Blood

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In past years, a diagnosis of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant (HCT) conferred nearly universal mortality secondary to lack of consensus for diagnostic criteria, poorly understood disease pathogenesis, and very few studies of therapeutic or supportive care interventions. Recently, however, progress has been made in these areas: revised consensus diagnostic guidelines are now available, supportive care has improved, there is greater understanding of potential mechanisms of disease, and prospective trials are being conducted. This article describes these advances and provides suggestions to optimize therapy for patients with BOS after HCT.

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Section: 305253mentioning

confidence: 99%

How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Williams

2017

Blood

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“…A shift from pro-to anti-inflammatory and anti-fibrotic cytokines was observed, levels of CCL2 and TGF-beta decreased, while the levels of IL-1Ra, IL-10, and HGF increased. Interestingly, we found a direct positive correlation between the reduction in IL-17 levels and skin thickness measured by ultrasonography [7]. Furthermore, we reported improvement in in vitro suppressor capacity of Treg cells after the treatment cycles, and a direct negative correlation between modified Rodnan skin score and Tr1 cell ratios, as well [8,9].…”

Section: Introductionmentioning

confidence: 56%

“…Our workgroup was the first to investigate the immunomodulatory effects of ECP in SSc patients [7]. Based on our former clinical and laboratory observations in SSc [8], we performed a wide spectrum of analyses, ranging from clinical evaluation to serological markers and immunocompetent cell analyses.…”

Section: Introductionmentioning

confidence: 99%

The assessment of immune-regulatory effects of extracorporeal photopheresis in systemic sclerosis: a long-term follow-up study

et al. 2015

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The therapeutic options in systemic sclerosis (SSc) are limited mainly to the management of complications, and decelerating fibrosis and preventing disease progression are still great challenges. Extracorporeal photopheresis (ECP) is one of the promising therapeutic strategies in SSc; nevertheless, there is no consensus on the ideal timing and frequency of treatment cycles. In the present study, we evaluated the long-term effects of consecutive ECP treatments, and the stability of clinical and laboratory improvements. We enrolled nine patients with diffuse cutaneous SSc and performed 12 ECP cycles (24 ECP treatments) per patient in total. ECP cycles were carried out once in every 6 weeks, and each cycle consisted of two procedures. Sixteen healthy individuals served as controls for laboratory assessment. Following the sixth ECP cycle, we observed further improvement in skin score, which was confirmed by high-resolution ultrasonography as well. After the second ECP cycle, values of Tr1 and CD4+CD25(bright) Treg cells increased; however, Tr1 cells remained under control values until the 10th cycle. Suppressor activity of CD4+CD25+ Treg cells improved, while percentages of Th17 cells decreased. At the end of 12-month follow-up, we did not observe significant deterioration in skin involvement; however, improvement in laboratory parameters diminished after 12 months. If the first six ECP cycles are effective, uninterrupted continuation of treatment should be considered, which may lead to the normalization of Tr1 cell values along with further clinical improvement. Our laboratory observations indicate that immunomodulatory effect of ECP treatments lasts for 1 year only.

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“…On the pro-inflammatory side, T-cells have the ability to differentiate into IL-17-producing T Since altered Th17 and regulatory T cell ratios may play a pathogenic role by tipping the fine balance toward enhanced immune reactivity, the disruption of this equilibrium has been studied in various systemic autoimmune conditions [32][33][34][35]. In order to assess whether a shift in the cytokine homeostasis exists in autoimmune conditions, fueling the predominance of pro-inflammatory cells vs. immunoregulatory T-cells, we have measured a broad spectrum of circulating cytokines in patients with various systemic autoimmune and rheumatic diseases [36][37][38][39][40][41].…”

Section: Th17 Cells and The Th17/treg Ratio In Systemic Autoimmune DImentioning

confidence: 99%

“…The Th17 cell and regulatory T cell imbalance, along with impaired circulating cytokine profile gives a good ground to use these parameters for therapy response assessment in SSc. Extracorporeal photochemotherapy (ECP) is a useful therapeutic modality in SSc, therefore we enrolled patients with diffuse cutaneous SSc, whom received 12 ECP treatments in total and assessed various immunocompetent celltypes, including regulatory cells and Th17 cells using intracellular cytokine staining [62]. We could see significant 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 …”

Section: Regulatory T-cells and The Cytokine Milieu In The Pathogenesmentioning

confidence: 99%

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Nakken

Bodolay

Szodoray

2014

Clinic Rev Allerg Immunol

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Undifferentiated connective tissue disease (UCTD) is a unique clinical entity, a potential forerunner of well-established systemic autoimmune/rheumatic diseases. UCTD is characterized by the presence of various clinical symptoms, as well as a diverse repertoire of autoantibodies, resembling systemic autoimmune diseases. Since approximately one-third of these patients consequently transform into a full-blown systemic autoimmune/rheumatic disease, it is of major importance to assess pathogenic factors leading to this progression. In view of the fact that the serological and clinical picture of UCTD and systemic autoimmune diseases are very similar, it is assumed that analogous pathogenic factors perpetuate both disease entities. In systemic autoimmune conditions a quantitative and qualitative impairment of regulatory T cells have been shown previously and in parallel a relative dominance of proinflammatory Th17 cells has been introduced. Moreover the imbalance between regulatory and Th17 cells plays a pivotal role in the initiation and propagation of UCTD. Additionally, we depict a cytokine imbalance, which give raise to a biased T-cell homeostasis from the UCTD phase throughout the fully developed systemic autoimmune disease stage. The levels of IL-6, IL-12, IL-17, IL-23 and IFN- were pathologically increased with a parallel reduction of IL-10. We believe that the assessment of Th17/Treg cell ratio, as well as the simultaneous quantitation of cytokines may give a useful diagnostic tool at the early UCTD stage to identify patients with a higher chance of consecutive disease progression towards serious systemic autoimmune diseases. Moreover, the early-targeted immunomodulating therapy in these patients may decelerate, or even stop this progression, before the development of serious autoimmune conditions with organ damage.

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Immunomodulatory effects of extracorporeal photochemotherapy in systemic sclerosis

Cited by 47 publications

References 21 publications

How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

The assessment of immune-regulatory effects of extracorporeal photopheresis in systemic sclerosis: a long-term follow-up study

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

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