Sarcoidosis Clinical Trial
Official title:
Pathogen Specific Immunity in Sarcoidosis
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.
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.
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Observational Model: Case-Only, Time Perspective: Prospective
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