Biomarkers in Systemic Histiocytosis

Not yet recruiting

• Conditions: Systemic Histiocytosis (Disorder)

• Registration Number: NCT07157683
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Systemic histiocytoses in adults (Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease) are rare inflammatory disorders in which recent discoveries have identified a clonal origin, with activating mutations in the MAP kinase pathway, enabling access to targeted therapies. However, the mechanism by which these mutations induce an inflammatory profile in tissue histiocytes remains largely unknown.

Despite these advances, there is a clear need to refine diagnostic and prognostic classification, to identify the biological mechanisms involved in the onset and progression of these diseases, to develop new targeted strategies, and to establish minimally invasive monitoring methods (liquid biopsies).

This project aims to make a decisive contribution toward these goals.

Detailed Description

Systemic histiocytoses are rare diseases with a clinical spectrum ranging from mild forms to severe, life-threatening multi-organ involvement. Numerous recent studies have identified somatic mutations in the MAP kinase pathway in tissue-infiltrating histiocytes, providing a better understanding of the disease pathophysiology and enabling access to more effective targeted therapies. However, due to the extreme rarity of these diseases, many unknowns remain.

These mutations do not appear to induce a proliferative oncogenic process, as seen in cancers where similar mutations have been identified. Instead, they seem to trigger a pro-inflammatory and pro-fibrotic immune response, ultimately leading to organ damage. The immune mechanisms induced by these mutations in histiocytes remain unexplored.

There are also currently no reliable data to accurately predict disease progression, including survival, treatment response, remission, or organ involvement.

It is therefore essential to establish patient cohorts to improve disease understanding and to identify effective diagnostic, prognostic, and predictive biomarkers-whether for standard treatment response or as potential theranostic markers (actionable by a specific treatment).

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-23
• Study First Submitted QC: 2025-09-02
• Last Update Submitted: 2025-09-02
• Study First Posted: 2025-09-05
• Last Update Posted: 2025-09-05
• Study Start: 2025-10-01
• Primary Completion: 2040-10-01
• Study Completion: 2040-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Age ≥ 18 years
• Patient followed for systemic histiocytosis in Internal Medicine Department 2 at Pitié-Salpêtrière Hospital
• Non-opposition to participation in the study

Exclusion Criteria

• Pregnant or breastfeeding women
• Patients without French social security or covered by State Medical Aid (AME)
• Patients deprived of liberty by judicial or administrative decision, or under legal protection

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identification of new biomarkers involved in histiocytosis	10 years	Plasma concentrations of several cytokines and chemokines involved in inflammation and fibrosis will be assessed using ELISA and Luminex assays (CSF, EGF, GM-CSF, FGF-basic, IFN-α, MCP-1, HGF, IFN-γ, MIG, VEGF, IL-1β, MIP-1α, IL-1RA, MIP-1β, IL-2, RANTES, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17, TNF-α, and Eotaxin),

Secondary Outcome Measures

Name	Time	Method
Identification of new biomarkers involved in histiocytosis	10 years	using flow cytometry and mass cytometry analyses of 37 immune cell subsets using a dedicated 30-marker panel.
Description of the correlation between the identified biomarkers and clinical manifestation of histiocytosis	10 years
Description of the correlation between the identified biomarkers and prognosis of histiocytosis	10 years	like mortality, or organ damage
Description of the correlation between the identified biomarkers and response to treatment	10 years	complete response, partial response, stable disease, disease progression

Trial Locations

Locations (1)

Internal Medicine Department 2 at Pitié-Salpêtrière Hospital; 🇫🇷 Paris, France