{
  "abstract": "Introduction Systemic sclerosis (SSc) is a rare, chronic autoimmune disease characterized by fibrosis of the skin and/or internal organs. While its pathogenesis remains incompletely understood, increasing evidence suggests a dominance of T-helper 2 (TH2) immune responses. For patients with severe, rapidly progressive disease, autologous hematopoietic stem cell transplantation (HSCT) has emerged as an effective therapeutic option, despite a therapy-associated mortality of up to 12%. The precise immunological mechanisms by which HSCT exerts its effects remain unclear.Material and Methods We conducted immunological and clinical analyses in a cohort of up to 35 SSc patients before and up to 3 years after HSCT. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with antigens known to induce specific T-helper pathways. Lymphocyte proliferation and cytokine secretion were assessed using two distinct assay formats. The primary endpoint was defined as a statistically significant reduction (p < 0.05) in TH2-associated proliferation and/or cytokine expression post-HSCT. The secondary endpoint examined a shift in cytokine patterns indicative of TH2 phenotype loss. Exploratory endpoints included clinical evaluation using the modified Rodnan Skin Score (mRSS) and correlations between immunological profiles and clinical outcomes.Results One year post-HSCT, a significant reduction in TH2 immune activity was observed. Furthermore, a loss of the TH2 phenotype was documented in all six previously TH2-polarized patients. An increase in the anti-inflammatory cytokine IL-10 and a decrease in pro-inflammatory GM-CSF levels were also detected. Clinically, a significant reduction in mRSS was observed as early as 3 months post-HSCT and was sustained for up to 3 years. Subgroup analyses revealed that patients experiencing clinical relapse (increased mRSS) had shown a reversion to a TH2-dominated immune profile shortly beforehand. Notably, all patients initially exhibiting a TH2-polarized phenotype showed a switch to TH0 post-HSCT, and four out of five of these patients showed clinical improvement.Conclusions Our study demonstrates a significant post-HSCT reduction in TH2 activity and a corresponding clinical benefit in SSc patients, supporting the hypothesis that modulation of T-helper cell polarization is a key mechanism of HSCT. These findings align with prior smaller studies but represent the largest long-term dataset of its kind. Future research should focus on correlating immunological subtypes with clinical outcomes to enhance patient selection and safety. Flow cytometric cytokine profiling may serve as a practical tool for routine immunomonitoring in clinical settings.",
  "authors": [
    {
      "affiliations": [
        "University Hospital Tübingen, Department Internal Medicine 2, Tübingen, Germany"
      ],
      "name": "Olschner Johannes"
    },
    {
      "affiliations": [
        "University Hospital Tübingen, Department Internal Medicine 2, Tübingen, Germany"
      ],
      "name": "Pecher Ann-Christin"
    },
    {
      "affiliations": [
        "University Hospital Tübingen, Department Internal Medicine 2, Tübingen, Germany"
      ],
      "name": "Klein Reinhild"
    },
    {
      "affiliations": [
        "University Hospital Tübingen, Department Internal Medicine 2, Tübingen, Germany"
      ],
      "name": "Henes Jörg"
    }
  ],
  "title": "P.258 Reduction of TH2 overexpression after stem cell transplantation is associated with clinical response",
  "uid": "132667e4-1f69-5b39-9fa8-db3a7705cac7"
}