Biomarkers in Systemic Histiocytosis (Bio-Histio)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Histiocytosis (Disorder)
• Intervention / Treatment: Other: Biospecimen collection

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 Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Internal Medicine Department 2 at Pitié-Salpêtrière Hospital
    • Contact: Matthias PAPO, MD,PhD; Phone Number: +33 1 84 82 81 73; Email: matthias.papo@aphp.fr
    • Contact: Julien HAROCHE, MD,PhD; Phone Number: +33 1 84 82 62 25; Email: julien.haroche@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with systemic histiocytosis

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of new biomarkers involved in histiocytosis	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),	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of new biomarkers involved in histiocytosis	using targeted transcriptomic profiling: total RNAseq using the Human Immunology v2 panel (Nanostring, 594 genes),	10 years
Identification of new biomarkers involved in histiocytosis	using single-cell RNA sequencing	10 years
Identification of new biomarkers involved in histiocytosis	using flow cytometry and mass cytometry analyses of 37 immune cell subsets using a dedicated 30-marker panel.	10 years
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	like mortality, or organ damage	10 years
Description of the correlation between the identified biomarkers and response to treatment	complete response, partial response, stable disease, disease progression	10 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): October 1, 2040
• Study Completion (Estimated): October 1, 2040

Study Registration Dates

• First Submitted: July 23, 2025
• First Submitted That Met QC Criteria: September 2, 2025
• First Posted (Estimated): September 5, 2025

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: histiocytosis
• Additional Relevant MeSH Terms: Lymphatic Diseases; Hemic and Lymphatic Diseases; Histiocytosis
• Other Study ID Numbers: APHP250660

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No