Immunological Reconstitution after Autologous Hematopoietic Stem Cell Transplantation in Patients with Systemic Sclerosis: Relationship Between Clinical Benefits and Intensity of Immunosuppression

Abstract

Our results suggest that immunosuppression intensity, sufficient to induce transient suppression of thymic function, is attributable to the feasible clinical response in patients with SSc treated with autologous HSCT. Appropriate monitoring of sjTREC values may predict clinical benefits in transplanted SSc patients after autologous HSCT.

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

“…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.…”

“…Few studies with different methods, each of them in a small number of patients, have analyzed the immune reconstitution process after aHSCT for various types of autoimmune disease, including multiple sclerosis, 35 SSc, 29,30 juvenile arthritis 36 and SLE. 37 All studies reported that long-term remission in patients who received aHSCT was associated with a de novo regeneration of the T-cell compartment that can be delayed for years after T-cell depleting conditioning for aHSCT.…”

“…27,28 After aHSCT, the clinical regression of skin fibrosis has been correlated with reappearance of functional B cells, thymic and extrathymic T-cell development, reconstitution of effector cells and efficient antigen presentation to reconstitute the pretransplantation immune repertoire. 29,30 However, further analysis of the immune reconstitution of the various Treg subsets and their function after aHSCT in SSc patients is warranted.…”

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

“…Persistent increase of Th1/Th2 ratios, 58 recovery of Treg function, 14 changes in thymic output, 19,33,59 and lower profibrotic serum cytokine levels 60 have been described. Several questions still remain, especially concerning the immunological determinants of clinical outcomes.…”

Treatment of systemic sclerosis: potential role for stem cell transplantation

“…59 Additionally, a new study demonstrated immunological reconstitution obtained from suppression of thymic function after autologous HSCT in 10 patients with SSc, assessed by quantification of signal joint T cell receptor rearrangement excision circles (sjTREC). 60 The protocols of the ASTIS and SCOT trials are similar in their selection criteria, primary outcome and control arms, but differs in the conditioning regimens. ASTIS utilizes cyclophosphamide 200 mg/kg body weight and rabbit ATG, and SCOT uses cyclophosphamide 129 mg/kg body weight, equine ATG, and radiation of 800 cGy (with shielding of the lungs and kidney).…”