Pathogen Specific Immunity in Patients With Sarcoidosis
Condition: Sarcoidosis
MeSH terms: Sarcoidosis
Study type: Observational

Summary: 
      The purpose of this study is to assess the lung cells of healthy volunteers and patients with
      stage II and III pulmonary sarcoidosis for pathogen specific memory immunity and gene
      expression patterns.
    

Detailed description: 
      BACKGROUND:

      Since its initial description 125 years ago, sarcoidosis continues to be a "challenging"
      disease. Its etiology remains unknown. Discovering the etiology of sarcoidosis remains a
      major goal with important implications regarding treatment, predicting outcome, as well as
      determining approaches for preventive measures. Immunological responses and granulomatous
      tissue formation characterizing sarcoidosis are similar to those observed in a variety of
      infectious diseases. However, the nature of the specific antigen(s), which putatively trigger
      the inflammatory response in sarcoidosis, remains elusive. Occurrence of sarcoidosis in
      spatially related clusters, and household and health care settings strongly support
      person-to-person transmission of an infectious agent as one of the potential causes of this
      disease. Sarcoidosis has been associated with a variety of infectious agents, none of which
      can be cultured. Propionibacterium acnes (P. acnes) and M.tuberculosis (Mtb) are the most
      commonly identifiable infectious pathogens by PCR-based methods and considered to be
      associated with the development of this disease. Immunological studies in sarcoidosis have
      focused largely on the assessment of constitutive, immune responses and the description of
      the phenotypes of blood and lung cells in patients and control subjects.

      DESIGN NARRATIVE:

      This study will utilize memory immune responses as search tools for the 'immunological
      imprints' from P. acnes or Mtb exposure. Peripheral blood mononuclear cells and
      bronchoalveolar cells will be compared from patients with stage II and/or stage III
      sarcoidosis and from healthy control subjects. Investigators will use ELISPOT assay to study:
      (1) frequencies of pathogen-specific interferon-7 and interleukin-10-producing cells, and (2)
      utilizing P. acnes- or Mtb-infected autologous monocytes and alveolar macrophages as target
      cell frequencies of pathogen-specific granzyme B-releasing cytotoxic T lymphocytes and
      natural killer cells. Finally, investigators will test the feasibility of identifying by DNA
      micro array, pathogen specific, transcriptional host gene expression profiles in P. acnes-
      and Mtb-stimulated blood cells from healthy control subjects and patients with active
      sarcoidosis and to compare these with gene expression profiles from autologous, unstimulated
      in situ lung cells. The studies will address the role of P. acnes and Mtb in the etiology of
      sarcoidosis and will also serve as a basis or model for future work involving other possible
      infectious or non-infectious pathogens/antigens for the development of sarcoidosis.
    

Intervention name(s): Bronchoalveolar Lavage and Venipuncture
Intervention type(s): Procedure
Intervention MeSH terms: Dimercaprol
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Sarcoidosis patients and healthy subjects