Secondary Adult's Hemophagocytic Lymphohistiocytosis and Innate Immunity

Hemophagocytic lymphohisticytosis (HLH) is a rare and severe disease of genetic origin in children (familial-HLH, F-HLH) or affecting adults secondary to infections, hematologic malignancies or auto-immune diseases (secondary_HLH, S-HLH). F-HLH are due to genetic mutations affecting the genes of perforin or proteins involved in its secretion, resulting in the complete loss of lymphocyte cytotoxicity without affecting lymphocyte number. In S-HLH, the investigators have observed a severe NK cell lymphopenia and a transient loss of cytotoxicity of unknown mechanism. In this study, the investigators will dissect macrophage activation mechanisms as well as NK cytotoxicity inability in adults patients suffering of S-HLH.

Macrophage activation could result from the loss of the retro-control normally exerted by NK cells, thus the investigators will analyze reciprocal interactions of macrophages and NK cells during the acute phase and after recovery of S-HLH.

Study Overview

• Status: Completed
• Conditions: Hemophagocytic Lymphohisticytosis
• Intervention / Treatment: Other: blood sample

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Marseille, France
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients Hemophagocytic lymphohisticytosis group:

• Of more than 18 years old
• affected by secondary LH infections with the exception of the HIV, the lymphomes, the néoplasies or the autoimmunes / inflammatory diseases following the criteria of the HLH Society modified in 2004

group control

• Of more than 18 years old
• At the time of the diagnosis either of firstly viral infection (EBV, CMV, parvovirus B19, HSV), is of lymphome cunning(malignant) not - Hodgkinien or of epithelial métastasés cancers, or auto-immune disease (erythemic lupus and disease of Still of the adult only) without associated criteria corresponding to the diagnosis of LHS
• have agreed to benefit from a pregnancy test and from a screening sérologique by the infection by the HIV. These tests that must be negative. In case of positivity of the screening HIV, the patients will be directed to an adequate service.
• Have still received no preliminary treatment for this pathology
• Have agreed to participate in the study and to have signed the form of consent

group healthy control They will have to be unhurt of active infectious pathology, hématologique, auto-immune or neoplastic and have by receipt of immunosuppresseurs treatments during the last 2 years.

Exclusion Criteria:

Patients Hemophagocytic lymphohisticytosis group:

• Minor patients under age 18 or vulnerable (encircled women, private persons of freedom judicially or administratively, adults under guardianship, under guardianship and to express their consent)
• histories of established LHF or episode of LH during the childhood
• patients reached(affected) by infection by the HIV: either histories known for seropositivity and / or of disease, or because of the positivity of the test sérologique realized in the inclusion after consent of the patient.
• Have already benefited from a specific treatment of the LHS

group control

Patients under age 18 and not to belong in one group of vulnerable persons (encircled women, private persons of freedom judicially or administratively, adults under guardianship, under guardianship and to express their consent)

• Patients answering the criteria of diagnosis of LHS
• Patients having already had histories of LH
• Patients having already received the specific treatments of these diseases
• patients reached(affected) by infection by the HIV: either histories known for seropositivity and / or of disease, or because of the positivity of the test sérologique realized in the inclusion after consent of the patient.

group healthy control Patients under age 18 and not to belong in one group of vulnerable persons (encircled women, private persons of freedom judicially or administratively, adults under guardianship, under guardianship and to express their consent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: patients Hemophagocytic lymphohisticytosis group	Other: blood sample
OTHER: group control patient	Other: blood sample
OTHER: healthy control group	Other: blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the cytotoxicité lymphocytaire	To compare the cytotoxicité lymphocytaire at the patients affected by LHS with regard to 2 groups of subjects controls: a group of patients affected by infections except HIV, by hémopathies or by epithelial métastasés cancers, by autoimmunes / inflammatory pathologies (spread erythemic lupus and disease of Still of the adult) but having no LHS (controls-patients) and a group of healthy subjects.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of the mechanisms of the activation macrophagique	Study of the mechanisms of the activation macrophagique	3 years

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: jean robert HARLE, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: May 17, 2010
• First Submitted That Met QC Criteria: May 17, 2010
• First Posted (ESTIMATE): May 18, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 1, 2015
• Last Update Submitted That Met QC Criteria: June 30, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: 2007/35; 2007-A01109-44 (REGISTRY: 2007/35)