Idiopathic CD4 Lymphocytopenia

NCT02113930 | Completed

• 1 other identifier: NI08039
• Study Type: observational
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Idiopathic CD4 Lymphocytopenia

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  1 year

Secondary Outcomes (4)

• Response to IL-2 or IL-7 treatment

  1 year

• Incident cases of ICL in first degree relatives

  1 year

• Thymic volume and correlation with CD4+ level

  1 year

• Analysis of differentiation and activation of T and B lymphocytes

  1 year

Study Arms (2)

Idiopathic CD4 lymphocytopenia

Constitution of a biobank of frozen cells, plasma and serum samples

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)

Genetic: Genetic study

Interventions

Constitution of a biobank of frozen cells, plasma and serum samples BIOLOGICAL

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).

Idiopathic CD4 lymphocytopenia

Genetic study GENETIC

High rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC)

Genetic Study

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

200 patients will be included : 100 for which the diagnosis of ICL will be defined on a basis in international classification criteria.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Cochin Hospital

Paris, 75014, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Serum; plasma, peripheral blood mononuclear cells and DNA.

MeSH Terms

Conditions

T-Lymphocytopenia, Idiopathic CD4-Positive

Interventions

Genetic Association Studies

Condition Hierarchy (Ancestors)

Lymphopenia; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Genetic Techniques; Investigative Techniques

Study Officials

• Luc Mouthon, MD, PhD

  Cochin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2013
• First Posted: April 15, 2014
• Study Start: September 10, 2013
• Primary Completion: September 6, 2017
• Study Completion: September 6, 2017
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

FR (1)