Cell therapy for autoimmune diseases: does it have a future?

Radbruch, Andreas; Thiel, Andreas

doi:10.1136/ard.2004.028340

Cited by 16 publications

(9 citation statements)

References 37 publications

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“…The immune reconstitution process after aHSCT is associated with the reemergence of naive T cells, the depletion of autoreactive memory T cells, the regeneration of thymic-derived FoxP3 þ regulatory T cells and the recovery of the naive B-cell compartment. 29,30,35,38 Two important observations for SSc patients treated by aHSCT emerged from the present pilot study: first, both nTreg and aTreg cells regenerated to frequencies comparable with those in normal controls; second, the renewal of Treg subsets was associated with a restoration of nTreg suppressive capacity, as reported by Zhang et al 34 in SLE patients treated by aHSCT. Altogether, our data support the 'resetting' of the adaptive immune system induced by aHSCT, as previously reported for other types of autoimmune diseases treated by aHSCT and always based on the analysis of a small number of patients.…”

Section: Controlsupporting

confidence: 59%

Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study

Baraut

Grigore

Jean-Louis

et al. 2013

Bone Marrow Transplant

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The present pilot study aims to evaluate the frequency and the function of regulatory T (Treg) cells in patients with diffuse cutaneous SSc (dcSSc) before and after autologous hematopoietic SCT (aHSCT). Peripheral blood lymphocytes from seven dcSSc patients were analyzed before and 24 months after aHSCT and were compared with those from seven healthy donors (controls).Treg (aTreg) cell subsets was performed using four-color flow cytometry. Treg-suppressive capability was measured after coculture with autologous T effector cells by evaluation of T-cell proliferation using 3 H-thymidine incorporation. Peripheral CD4 þ CD25 high FoxP3 þ (2 ± 0.5 vs 4.2 ± 1.1, Po0.01), CD4 þ CD25 þ TGF-b þ (6.9 ± 1.8 vs 14.6 ± 5.0, Po0.05) and CD4 þ CD25 þ IL-10 þ (10.7 ± 0.5 vs 16.1±3.2, Po0.01) Tregs as well as CD4 þ CD25 high CD127 low Tregs suppressive capacity (Po0.05) were decreased in dcSSc patients vs controls. After aHSCT (n ¼ 7), the percentages of CD4 þ CD25 high FoxP3 þ (4.1 ± 1.8) and CD4 þ CD25 þ IL-10 þ (15.7 ± 2.2) Treg cells and the suppressive activity of CD4 þ CD25 high CD127 low were restored to the levels in controls. The decreased frequency and the functional defect of peripheral Treg cells from patients with dcSSc are reversed following aHSCT to reach those observed in controls. This pilot study brings evidence of an effective restoration of nTreg and aTreg subsets, and recovery of nTreg suppressive function following aHSCT.

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Section: Controlsupporting

confidence: 59%

Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study

Baraut

Grigore

Jean-Louis

et al. 2013

Bone Marrow Transplant

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“…Diseases such as rheumatoid arthritis and insulindependent diabetes mellitus also showed strong statistical associations with certain MHC class II alleles, which was suggestive of a T cell-dependent process. However, a break with the fixation on the role of T cells in autoimmune disorders came when anti-T cell therapy failed to produce desirable clinical results in certain systemic autoimmune diseases [4]. B-cells on the other hand, were initially thought to be minor players that acted more as part of the effector arm of the autoimmune process, as was evident from the excessive production of (auto)antibodies in patients with autoimmune disorders.…”

mentioning

confidence: 99%

B-cell populations and sub-populations in Sjögren's syndrome

2012

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“…However, it has now become evident, in the setting of HSCT, that high-dose cyclophosphamide for mobilization, followed by conditioning and stem cell infusion both aim at resetting the autoimmune response and inducing long-term tolerance via fundamental changes of the immune system. 37,38 Indeed, several translational studies have shown that clinical improvements after HSCT in patients with SSc, 39 MS, 40 JIA, 41 and SLE 42 patients can be associated with drastic reactivation of thymic activity, including the restoration of a new polyclonal T-cell repertoire [39][40][41] and de novo induction of thymus-derived natural Treg cells 40,41 which are essential for restoration of peripheral tolerance for autoantigens, or with the elimination of autoantibodyproducing cells. …”

Section: -Day Transplant-relatedmentioning

confidence: 99%

Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases

Farge¹,

Labopin²,

Tyndall³

et al. 2009

Haematologica

328

268

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BackgroundAutologous hematopoietic stem cell transplantation has been used since 1996 for the treatment of severe autoimmune diseases refractory to approved therapies. We evaluated the long-term outcomes of these transplants and aimed to identify potential prognostic factors. Design and MethodsIn this observational study we analyzed all first autologous hematopoietic stem cell transplants for autoimmune diseases reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 1996-2007. The primary end-points for analysis were overall survival, progression-free survival and transplant-related mortality at 100 days. ResultsNine hundred patients with autoimmune diseases (64% female; median age, 35 years) who underwent a first autologous hematopoietic stem cell transplant were included. The main diseases were multiple sclerosis (n=345), systemic sclerosis (n=175), systemic lupus erythematosus (n=85), rheumatoid arthritis (n=89), juvenile arthritis (n=65), and hematologic immune cytopenia (n=37). Among all patients, the 5-year survival was 85% and the progression-free survival 43%, although the rates varied widely according to the type of autoimmune disease. By multivariate analysis, the 100-day transplant-related mortality was associated with the transplant centers' experience (P=0.003) and type of autoimmune disease (P=0.03). No significant influence of transplant technique was identified. Age less than 35 years (P=0.004), transplantation after 2000 (P=0.0015) and diagnosis (P=0.0007) were associated with progression-free survival. ConclusionsThis largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with the transplant centers' experience. These data support ongoing and planned phase III trials to evaluate the place of autologous hematopoietic stem cell transplantation in the treatment strategy for severe autoimmune diseases.Key words: autologous hematopoietic stem cell transplantation, autoimmune diseases, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, hematologic immune cytopenia, total body irradiation, antithymocyte globulins, cyclophosphamide. Citation: Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J, Ouyang J, Kozak T, Moore J, Kötter I, Chesnel V, Marmont A, Gratwohl A, and Saccardi R. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party onAutoimmune Diseases. Haematologica. 2010;95:284-292. doi:10.3324/haematol.2009

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Cell therapy for autoimmune diseases: does it have a future?

Cited by 16 publications

References 37 publications

Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study

Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study

B-cell populations and sub-populations in Sjögren's syndrome

Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases

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