Abstract
INTRODUCTION: Systemic sclerosis (SSc) is a rare autoimmune disease characterised by skin and organ fibrosis, vasculopathy and immune dysregulation. Given the disease heterogeneity and severity, accurate prognostic and predictive markers are needed. Blood immunophenotyping by flow or mass cytometry offers a promising non-invasive approach to identify immune signatures associated with disease subtypes, complications (eg, interstitial lung disease, scleroderma renal crisis, digital ulcers) and treatment responses. However, findings remain inconsistent and lack clinical standardisation. This systematic review aims to identify cytometry-based blood immune markers associated with clinical outcomes in SSc. METHODS AND ANALYSIS: A comprehensive search will be conducted on three databases: PubMed, Web of Science and Cochrane Library, from their inception to the date of the final search (21 December 2025). Data will be extracted and analysed using a predefined charting form. Studies published in English or French reporting the use of flow or mass cytometry for peripheral blood cells phenotyping in adults with SSc will be included. Comparators will include healthy controls, other autoimmune diseases, disease severity groups and treatment response subgroups. The primary outcome will be the association with the diffuse cutaneous subtype, while secondary outcomes will include overall survival and disease-specific mortality, organ involvement, progression of the disease and treatment response. ETHICS AND DISSEMINATION: Ethical approval is not required as this review is an analysis of published scientific literature and does not involve patients. The results of this systematic literature review will be submitted for publication in a peer-reviewed journal and presented at relevant conferences. PROSPERO REGISTRATION: CRD420250644594.