Systemic Histiocytosis (Disorder)
Conditions
Keywords
histiocytosis
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).
Interventions
OTHERBiospecimen collection
If a blood sample is drawn as part of standard care, up to six additional EDTA tubes (42 mL max) will be collected for research. In addition, the following optional samples may be collected, depending on investigator assessment and/or patient preference: * Saliva sample (if no blood draw is performed) * Urine sample * Stool sample
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Identification of new biomarkers involved in histiocytosis | 10 years | using targeted transcriptomic profiling: total RNAseq using the Human Immunology v2 panel (Nanostring, 594 genes), |
| 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 |
Countries
France
Outcome results
None listed