Genomic Research in Sarcoidosis
Condition: Sarcoidosis
MeSH terms: Sarcoidosis
Study type: Observational

Summary: 
      This project is designed to address the following hypothesis:

      Distinct patterns in lung microbiome are characteristic of sarcoidosis phenotypes and
      reflected in changes in systemic inflammatory responses as measured by peripheral changes in
      gene transcription.

      The Specific Aims are:

        1. To identify peripheral blood mononuclear cell (PBMC) gene expression patterns that
           characterize distinct sarcoidosis phenotypes.

        2. To determine whether patterns in the lung microbiome are associated with sarcoidosis
           severity and disease phenotypes

        3. To correlate mRNA and microRNA expression patterns in sarcoidosis affected organs with
           changes in microbiome, clinical parameters and PBMC gene expression patterns

        4. To integrate clinical, transcriptomic, and microbiome data to identify novel molecular
           phenotypes in sarcoidosis.
    

Detailed description: 
      Sarcoidosis is a systemic disease characterized by the formation of granulomatous lesions,
      especially in the lungs, liver, skin, and lymph nodes, with a heterogeneous set of clinical
      manifestations and a variable course 1. Despite significant progress in the understanding of
      the genetic predisposition and role of immunity, it is still a challenge to explain the
      clinical presentation of sarcoidosis. Standard clinical assessment, imaging, and pulmonary
      function tests (PFTs) do not allow prediction of disease course and response to therapy.
      Furthermore, there are no good long-term therapies. Considering that the interactions between
      potential infections, changes in systemic inflammation, and patterns in lung microbiome and
      the different and distinct disease phenotypes in sarcoidosis are not well understood, the
      Sarcoidosis protocol for the Genomic Research in AAT Deficiency and Sarcoidosis (GRADS) grant
      (hereafter called GRADS Sarcoidosis protocol) is designed to address the following:

      Hypothesis

      Distinct patterns in lung microbiome are characteristic of sarcoidosis phenotypes and
      reflected in changes in systemic inflammatory responses as measured by peripheral changes in
      gene transcription.

      Specific Aims

        1. To identify peripheral blood mononuclear cell (PBMC) gene expression patterns that
           characterize distinct sarcoidosis phenotypes.

        2. To determine whether patterns in the lung microbiome are associated with sarcoidosis
           severity and disease phenotypes

        3. To correlate mRNA and microRNA expression patterns in sarcoidosis affected organs with
           changes in microbiome, clinical parameters and PBMC gene expression patterns

        4. To integrate clinical, transcriptomic, and microbiome data to identify novel molecular
           phenotypes in sarcoidosis.

      Focusing on accessible PBMCs should enable GRADS researchers to identify markers for disease
      phenotypes, severity, and outcome. Analysis of lesional transcriptomes (mRNA, microRNA and
      lincRNA) will add mechanistic insights. High throughput unbiased analysis of the lung
      microbiome will potentially identify patterns in the lung microbiome that determine disease
      activity and persistence, as well as response to therapy.

      Participants are assigned a provisional clinical phenotype upon obtaining consent at time of
      enrollment by the respective recruiting center. Clinical phenotypes will be reviewed,
      confirmed, and monitored to ensure achievement of study objectives. Participants who cannot
      be assigned a clinical phenotype after the initial study visit will be excluded from
      additional study participation.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be prescreened for predefined clinical phenotypes of sarcoidosis. Those who
        meet initial criteria and ERS/ATS criteria for a sarcoidosis diagnosis will be recruited
        and phenotyped by questionnaire, physical exam, research chest CT exam, pulmonary function
        tests, and blood and urine tests with a total recruitment goal of 400.

        A subset of participants who have suspected pulmonary sarcoidosis, but who have not
        undergone a biopsy, will be recruited so that material may be obtained during their
        clinically indicated biopsy. If a diagnosis of sarcoidosis is confirmed, they will be
        enrolled and followed. If an alternative diagnosis is made, they will not undergo any
        further testing.

        Participants who cannot be classified within the clinical phenotypes based on data from the
        initial visit will not continue in the study. Recruitment of participants with defined
        clinical phenotypes will be monitored and ongoing recruitment goals adjusted to achieve
        overall study objectives.
      
Biospecimen description: 
      Serum, plasma, urine, stool, BAL fluid.
    
Keywords: Genomics; Microbiome; Microflora; Virome