Clinical Trial: Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia

Brief Summary:

Background:

• Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic infections or autoimmune disorders and diseases.

Objectives:

• To characterize the natural history with regard to CD4+ T cell count and onset of infection, malignancy, and autoimmunity.
• To describe the immunological status of patients affected by ICL while providing the best possible standard therapy to eradicate opportunistic infections.
• To establish the timeline of CD4 lymphocytopenia, with particular focus on defining subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell counts over time.
• To characterize the opportunistic infections that occur in ICL patients at microbiologic and molecular levels.
• To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL.
• To determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other comorbidities such as lymphoma in patients with ICL.
• To determine whether there is any association between ICL and autoimmunity.
• To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness in ICL patients.

Eligibility:

• Patients 2 years of age and older with an absolute CD4 count less tha
  

  Detailed Summary:

  Idiopathic CD4+ lymphocytopenia (ICL) is a disorder characterized by decreased numbers of circulating CD4+ T lymphocytes in the absence of known causes of CD4+ lymphocytopenia. ICL is defined as an absolute CD4+ T cell count of less than 300 cells/microliter in a patient with no human immunodeficiency virus infection or known immunodeficiency syndrome. The causes and frequency of the disorder remain unknown. The condition is typically diagnosed when patients present with a serious infection. In this natural history protocol, we will evaluate patients with CD4+ T cell counts below 300 cells/microliter. We propose to follow 200 ICL patients for a minimum of 4 and maximum of 14 years, with a particular focus on the association between ICL and autoimmune disease. In addition to the ICL patients we will enroll blood relatives and household contacts to better understand pathogenesis and etiologies of the syndrome. We will collect blood for immunologic, rheumatologic, and genetic testing in an effort to identify and understand the underlying defects that cause ICL and follow its course in a cohort of patients who will receive best standard therapy for opportunistic infections.

  Institutions:

  NIAID/NIH

  NIAID/LIR

  NIAMS/NIH

  CC/NIH

  
  Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
  

  Current Primary Outcome:
  
  

  Original Primary Outcome:
  
  

  Current Secondary Outcome:
  
  

  Original Secondary Outcome:
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: March 20, 2009
  Date Started: March 17, 2009
  Date Completion:
  Last Updated: April 20, 2017
  Last Verified: April 19, 2017