Idiopathic CD4 LymphocytopeniaLympho-4NCT02113930
Idiopathic CD4 Lymphocytopenia
An observational study of Idiopathic CD4 Lymphocytopenia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Definition: Idiopathic CD4+ T lymphocytopenia (ICL) is an immune deficiency first described in 1992 and characterized by the US Centers for Disease Control (CDC) as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Idiopathic CD4 Lymphocytopenia
- What is being tested?
- Constitution of a biobank of frozen cells, plasma and serum samples and Genetic study
- How many people
- 47 participants
- Where
- 1 siteFrance
- Study dates
- 10 Sep 2013to 6 Sep 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 200 patients will be included : 100 for which the diagnosis of ICL will be defined on a basis in international classification criteria.
Who may be able to join
- Idiopathic CD4 lymphocytopenia defined as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell lymphotropic 1/2 (HTLV-1/2); and lack of a defined immune-deficiency disease or therapy for lymphocytopenia.
- Male and female patients can be included
- Children and adults can be included
- Hospitalized or outpatient
Who cannot join
- CD4+ lymphocytopenia due to another condition (HIV infection, sarcoidosis, malignant lymphoma).
- Ongoing treatment possibly responsible for CD4 lymphocytopenia.
- CD4+ lymphocytopenia related to primary immune deficiency
- Absence of consent, of inability to obtain informed consent from the patients or the right holders.
- Absence of affiliation to a social security regimen of the patient or the right holder.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Analysis of Clinical and Immunological Characteristics, as Well as Pathophysiological Mechanisms in a French Cohort of Patients With Idiopathic CD4 Lymphocytopenia
Definition: Idiopathic CD4+ T lymphocytopenia (ICL) is an immune deficiency first described in 1992 and characterized by the US Centers for Disease Control (CDC) as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell lymphotropic 1/2 (HTLV-1/2); and lack of a defined immune-deficiency disease or therapy for lymphocytopenia. Epidemiologic, clinical and immunological characteristics of the syndrome were described in 1993 and ICL is now considered a heterogeneous syndrome not caused by an infectious agent. Patients with ICL may show opportunistic infections such as disseminated Cryptococcus neoformans infection, Pneumocystis jiroveci pneumonia and John Cunningham (JC) virus infection as a result of profound cell-mediated immune-response deficiency.
Few studies have focused on the pathophysiology of ICL. CD4+ T-lymphocyte phenotyping revealed increased CD95 expression that could be responsible for excess apoptosis leading to lymphocytopenia. Moreover, the membrane expression of C-X-C chemokine receptor type 4 (CXCR4) was found impaired in T lymphocytes with ICL, and CXCR4 trafficking was improved with interleukin 2 (IL-2) treatment in some patients. Recently, mutations in nunc119, MAGT1 and Rag were found associated with CD4+ T lymphocytopenia. In a prospective study of 39 patients, CD8+ T lymphocytopenia (<180/mm3) and degree of CD4+ T-cell activation measured by human leukocyte antigen DR (HLA-DR) expression was found associated with poor prognosis.
Read more
ICL is a heterogeneous disorder often associated with deficiencies in CD8+, CD19+, and/or NK cells. Long-term prognosis may be related to initial CD4+ and NK cell deficiency.
Larger studies are needed to better identify the patients who might benefit from IL-2 therapy. This is why the investigators conduct the Lympho-4 study, in which the investigators plan to include 200 patients with a suspected/proven diagnosis of ICL.
Read the detailed description
Definition. Idiopathic CD4+ T lymphocytopenia (ICL) is an immune deficiency first described in 1992 and characterized by the US Centers for Disease Control (CDC) as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell lymphotropic 1/2 (HTLV-1/2); and lack of a defined immune-deficiency disease or therapy for lymphocytopenia.
ICL is a heterogeneous disorder often associated with deficiencies in CD8+, CD19+, and/or NK cells. Thus, ICL does not correspond to a unique disease but more probably to a number of different conditions with distinct underlying mechanisms. This is why the investigators decided to launch the Lympho-4 study, in which the investigators plan to include 200 patients with a suspected/proven diagnosis of ICL.
The aim of the study will be to
- identify patients in whom the diagnosis of ICL is confirmed using an algorithm developed by a group of multidisciplinary experts.
- describe and compare clinical, immunological and follow up characteristics of patients in whom the diagnosis of ICL was confirmed vs patients in whom the diagnosis of ICL is not confirmed.
The investigators will also investigate :
Lymphocyte subpopulations including analysis of differentiation and activation of T and B lymphocytes, immortalisation of cell lineages with virus Epstein Barr virus, high rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC), constitution of a biobank of frozen plasma and serum samples ; investigation of the thymic volume by performing a CT scan.
Depending on clinical presentation and based on previous data obtained by our group, the investigators will investigate the immune responses against Human papilloma virus (HPV), Cryptococcus neoformans,implication of chemokines involved in lymphocyte migration (CXCR4 and CCR7 receptors) and signalisation in response to cytokines controlling LT CD4+ homeostasis (IL-7 et IL-2).
- Conditions
- Idiopathic CD4 Lymphocytopenia
- Being tested
- Constitution of a biobank of frozen cells, plasma and serum samples, Genetic study
- Medical subject headings
- T-Lymphocytopenia, Idiopathic CD4-Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Constitution of a biobank of frozen cells, plasma and serum samplesBiological
Depending on clinical presentation and based on previous data obtained by our group, we will investigate the immune responses against Human papilloma virus (HPV), Cryptococcus neoformans,implication of chemokines involved in lymphocyte migration (CXCR4 and CCR7 receptors) and signalisation in response to cytokines controlling LT CD4+ homeostasis (IL-7 et IL-2).
Genetic studyGenetic
High rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC)
| Study group | Role | What they receive |
|---|---|---|
| Idiopathic CD4 lymphocytopenia | Constitution of a biobank of frozen cells, plasma and serum samples Receives: Biological: Constitution of a biobank of frozen cells, plasma and serum samples | |
| Genetic Study | High rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC) Receives: Genetic: Genetic study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Idiopathic CD4+ T lymphocytopenia Diagnosis
Identify patients in whom the diagnosis of ICL is confirmed using an algorithm developed and applied by a multidisciplinary group of experts
Measured: 1 year
Clinical, immunological and follow up characteristics of all patients
Describe and compare clinical, immunological and follow up characteristics of patients in whom the diagnosis of ICL was confirmed as compared to those in whom the diagnosis of ICL was not confirmed.
Measured: 1 year
Secondary outcomes (4)
Response to IL-2 or IL-7 treatment
Describe the response to IL-2 or IL-7 treatment
Measured: 1 year
Incident cases of ICL in first degree relatives
Evaluate incident cases of ICL in first degree relatives of patients with ICL.
Measured: 1 year
Thymic volume and correlation with CD4+ level
Quantify thymic volume in patients with ICL and correlate it with CD4+ level.
Measured: 1 year
Analysis of differentiation and activation of T and B lymphocytes
Immortalisation of cell lineages with virus Epstein Barr virus, high rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC), constitution of a biobank of frozen plasma and serum samples ; investigation of the thymic volume by performing a CT scan.
Depending on clinical presentation and based on previous data obtained by our group, we will investigate the immune responses against Human papilloma virus (HPV), Cryptococcus neoformans,implication of chemokines involved in lymphocyte migration (CXCR4 and CCR7 receptors) and signalisation in response to cytokines controlling LT CD4+ homeostasis (IL-7 et IL-2).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2014 (estimated)
- Study start10 Sep 2013
- Primary completion6 Sep 2017
- Study completion6 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic CD4 LymphocytopeniaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Luc Mouthon, MD, PhD, Principal investigator, Cochin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02113930
- Sponsor's protocol ID
- NI08039
- Acronym
- Lympho-4
- Status last verified
- Mar 2026
- First submitted
- 28 Mar 2013
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Clinical and Immunological Characteristics, as Well as Pathophysiological Mechanisms in a French Cohort of Patients With Idiopathic CD4 Lymphocytopenia
- ClinicalTrials.gov ID
- NCT02113930
- Acronym / sponsor ID
- Lympho-4 / NI08039
- Conditions
- Idiopathic CD4 Lymphocytopenia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 10 Sep 2013 (actual)
- Primary completion
- 6 Sep 2017 (actual)
- Study completion
- 6 Sep 2017 (actual)
- First posted
- 15 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Definition: Idiopathic CD4+ T lymphocytopenia (ICL) is an immune deficiency first described in 1992 and characterized by the US Centers for Disease Control (CDC) as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell lymphotropic 1/2 (HTLV-1/2); and lack of a defined immune-deficiency disease or therapy for lymphocytopenia. Epidemiologic, clinical and immunological characteristics of the syndrome were described in 1993 and ICL is now considered a heterogeneous syndrome not caused by an infectious agent. Patients with ICL may show opportunistic infections such as disseminated Cryptococcus neoformans infection, Pneumocystis jiroveci pneumonia and John Cunningham (JC) virus infection as a result of profound cell-mediated immune-response deficiency.
Few studies have focused on the pathophysiology of ICL. CD4+ T-lymphocyte phenotyping revealed increased CD95 expression that could be responsible for excess apoptosis leading to lymphocytopenia. Moreover, the membrane expression of C-X-C chemokine receptor type 4 (CXCR4) was found impaired in T lymphocytes with ICL, and CXCR4 trafficking was improved with interleukin 2 (IL-2) treatment in some patients. Recently, mutations in nunc119, MAGT1 and Rag were found associated with CD4+ T lymphocytopenia. In a prospective study of 39 patients, CD8+ T lymphocytopenia (<180/mm3) and degree of CD4+ T-cell activation measured by human leukocyte antigen DR (HLA-DR) expression was found associated with poor prognosis.
ICL is a heterogeneous disorder often associated with deficiencies in CD8+, CD19+, and/or NK cells. Long-term prognosis may be related to initial CD4+ and NK cell deficiency.
Larger studies are needed to better identify the patients who might benefit from IL-2 therapy. This is why the investigators conduct the Lympho-4 study, in which the investigators plan to include 200 patients with a suspected/proven diagnosis of ICL.
Detailed description
Definition. Idiopathic CD4+ T lymphocytopenia (ICL) is an immune deficiency first described in 1992 and characterized by the US Centers for Disease Control (CDC) as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell lymphotropic 1/2 (HTLV-1/2); and lack of a defined immune-deficiency disease or therapy for lymphocytopenia.
ICL is a heterogeneous disorder often associated with deficiencies in CD8+, CD19+, and/or NK cells. Thus, ICL does not correspond to a unique disease but more probably to a number of different conditions with distinct underlying mechanisms. This is why the investigators decided to launch the Lympho-4 study, in which the investigators plan to include 200 patients with a suspected/proven diagnosis of ICL.
The aim of the study will be to
- identify patients in whom the diagnosis of ICL is confirmed using an algorithm developed by a group of multidisciplinary experts.
- describe and compare clinical, immunological and follow up characteristics of patients in whom the diagnosis of ICL was confirmed vs patients in whom the diagnosis of ICL is not confirmed.
The investigators will also investigate :
Lymphocyte subpopulations including analysis of differentiation and activation of T and B lymphocytes, immortalisation of cell lineages with virus Epstein Barr virus, high rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC), constitution of a biobank of frozen plasma and serum samples ; investigation of the thymic volume by performing a CT scan.
Depending on clinical presentation and based on previous data obtained by our group, the investigators will investigate the immune responses against Human papilloma virus (HPV), Cryptococcus neoformans,implication of chemokines involved in lymphocyte migration (CXCR4 and CCR7 receptors) and signalisation in response to cytokines controlling LT CD4+ homeostasis (IL-7 et IL-2).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Idiopathic CD4 lymphocytopenia | – | Biological: Constitution of a biobank of frozen cells, plasma and serum samplesConstitution of a biobank of frozen cells, plasma and serum samples |
| Genetic Study | – | Genetic: Genetic studyHigh rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 200 patients will be included : 100 for which the diagnosis of ICL will be defined on a basis in international classification criteria.
Key inclusion criteria (4 listed)
- Idiopathic CD4 lymphocytopenia defined as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell lymphotropic 1/2 (HTLV-1/2); and lack of a defined immune-deficiency disease or therapy for lymphocytopenia.
- Male and female patients can be included
- Children and adults can be included
- Hospitalized or outpatient
Key exclusion criteria (5 listed)
- CD4+ lymphocytopenia due to another condition (HIV infection, sarcoidosis, malignant lymphoma).
- Ongoing treatment possibly responsible for CD4 lymphocytopenia.
- CD4+ lymphocytopenia related to primary immune deficiency
- Absence of consent, of inability to obtain informed consent from the patients or the right holders.
- Absence of affiliation to a social security regimen of the patient or the right holder.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Constitution of a biobank of frozen cells, plasma and serum samplesDepending on clinical presentation and based on previous data obtained by our group, we will investigate the immune responses against Human papilloma virus (HPV), Cryptococcus neoformans,implication of chemokines involved in lymphocyte migration (CXCR4 and CCR7 receptors) and signalisation in response to cytokines controlling LT CD4+ homeostasis (IL-7 et IL-2). | Biological | Idiopathic CD4 lymphocytopenia |
| Genetic studyHigh rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC) | Genetic | Genetic Study |
Primary outcome
Idiopathic CD4+ T lymphocytopenia Diagnosis
Time frame: 1 year
Identify patients in whom the diagnosis of ICL is confirmed using an algorithm developed and applied by a multidisciplinary group of experts
Clinical, immunological and follow up characteristics of all patients
Time frame: 1 year
Describe and compare clinical, immunological and follow up characteristics of patients in whom the diagnosis of ICL was confirmed as compared to those in whom the diagnosis of ICL was not confirmed.
4 secondary outcomes
Response to IL-2 or IL-7 treatment
Time frame: 1 year
Incident cases of ICL in first degree relatives
Time frame: 1 year
Thymic volume and correlation with CD4+ level
Time frame: 1 year
Analysis of differentiation and activation of T and B lymphocytes
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luc Mouthon, MD, PhD principal investigator
Cochin Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Idiopathic CD4 Lymphocytopenia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Idiopathic CD4+ T lymphocytopenia Diagnosis (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2026; AzTrials last refreshed its copy on 26 Oct 2026.