HLH-genes: Children and Adult Hemophagocytic Syndrome (HLHa)
Study Details
Study Description
Brief Summary
Different study of HLHa patients :
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Diagnosis criteria, because criteria are based on pediatric genetic studies.
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Physiopathological studies: genetic studies have demonstrated the role of CD8+ cells, in particular because they have a genetic defect affecting their cytotoxic functions in HLH pediatric. the aim is to establish if the same defect is found in both some or in all of HLHa patients. If this is the case, to then establish whether hypomorphic genetic mutations are responsible.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Formation of a prospective and retrospective infant, adolescent and adult HLH patients cohort.
Collection of clinical and biological, therapeutics, informations, in a register, The collection of information is:
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To identify clinical and biological criteria specific to HLHa
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Classify patients into homogeneous groups, based on clinical biological scalability in particular, with regards to their response to treatment
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Identify and analyze the behavioral therapy Creation of a bank of biological samples for use in the study of the pathophysiology of HLHa.
Background:
The hemophagocytic syndrome in infant, adolescent and adults (HLH) is a serious and often lethal condition. The study of literature series HLHa shows that these syndromes frequently develop in immunocompromised patients (renal transplant, HIV, collagen in Processing immunosuppressants) in the course of a viral infection. HLH syndrome has also been described as a clinical form of lymphoma or connective disease (lupus). These clinical forms are rare, severe and recurrent suggesting the possibility that immune deficiency could be involved. The study of pediatric forms has definitely established a link between HLH syndrome and the presence of immune deficiency by identifying the nature of the latter. Four genetically determined diseases are manifested by HLH syndrome. These conditions are Family lymphohistiocytosis (LHF) syndrome, Chediak-Higashi CHS syndrome, Griscelli (GS) type 2 syndromes and X-linked lymphoproliferative (XLP 1 and 2). The mutated genes are respectively perforin Unc 13.4 and syntaxin in the LHF2, 3, 4 (10q locus genetic for LHF 1), CHS1/LYST (Lysosomal Trafficking regulator) in the CHS, in the Rab27a GS type 2, and XIAP and SH2D1A in the XLP. It is now well established that proteins encoded by these genes are necessary for the cytotoxic function of CD8 + and in the absence of these proteins is the cytotoxocity CD8
- deficient. Also, closed clinical and biological characteristics shared by pediatric genetic and adult forms suggest the existence of immune defects responsible for some or all HLH adult patients.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| hemophagocytic syndrome patient with hemophagocytic syndrome |
Biological: Identification of biological markers
|
Outcome Measures
Primary Outcome Measures
- biologicals criteria [T0 (before traitment]
measure of : cytokines expression (mmol/L) Hemoglobin (g/dl) number of Platelets (number/L) number of Neutrophils (number/L) number of triglycerides (mmol/L) number of fibrinogen (g/L) number of Ferritin (microg/L)
- name of treatment [T2 (T2 is the first day of treatment)]
administrated treatments
- Clinicals criteria [T0]
clinicals description of patients : Fever, Splenomegaly and adenopathy
- biologicals criteria [T1 (T1 is the first day of HLH syndrome)]
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
- biologicals criteria [T2 (T2 is the first day of treatment)]
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
- biologicals criteria [T4 (6 /12 months after the resolution of HLH)]
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
- Clinicals criteria [T1(T1 is the first day of HLH syndrome)]
clinicals description of patients : Fever, Splenomegaly and adenopathy
- Clinicals criteria [T2 (T2 is the first day of treatment)]
clinicals description of patients : Fever, Splenomegaly and adenopathy
- Clinicals criteria [T4 6 /12 months after the resolution of HLH)]
clinicals description of patients : Fever, Splenomegaly and adenopathy
- name of treatment [T4(6/12 month after resolution of HLH)]
administrated treatments
Eligibility Criteria
Criteria
Inclusion Criteria:
Major criteria:
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hemophagocytosis found in a specimen histology.
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Fever
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Splenomegaly
Minor criteria:
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adenopathy
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cytopenia> 2 cell lines Hemoglobin <9 g / dl (less than 4 weeks and> 12 g / dl) Platelets <100 000 x 10 / l Neutrophils <1 10 / l
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hypertriglyceridaemia and / or hypofibrinogenaemia Elevated triglycerides> 3 mmol / l Fibrinogen <1.5 g / l
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Ferritin> 500 microg / L
These criteria will be those used for the diagnosis of HLH in adults:
One major criterion and two minor (including hyper ferritin or hypertriglyceridemia) 3 minor criteria (including hyper ferritin or hypertriglyceridemia)
Exclusion Criteria:
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Pregnant women
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A person under guardianship
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Patients under the age of 2 years
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Research Unit | Paris | France | 75015 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
- Laboratory of normal and pathological development Immune System - IFR 94 U768
- Reference Centre for Hereditary Immunodeficiency: CEREDIH
Investigators
- Principal Investigator: Olivier Hermine, MD, PhD, Hopital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NI10015
- AOM 10219