Etiologies of Sarcoidosis

Clin Rev Allergy Immunol. 2015 Aug;49(1):6-18. doi: 10.1007/s12016-015-8481-z.


Since sarcoidosis was first described more than a century ago, the etiologic determinants causing this disease remain uncertain. Studies suggest that genetic, host immunologic, and environmental factors interact together to cause sarcoidosis. Immunologic characteristics of sarcoidosis include non-caseating granulomas, enhanced local expression of T helper-1 (and often Th17) cytokines and chemokines, dysfunctional regulatory T-cell responses, dysregulated Toll-like receptor signaling, and oligoclonal expansion of CD4+ T cells consistent with chronic antigenic stimulation. Multiple environmental agents have been suggested to cause sarcoidosis. Studies from several groups implicate mycobacterial or propionibacterial organisms in the etiology of sarcoidosis based on tissue analyses and immunologic responses in sarcoidosis patients. Despite these studies, there is no consensus on the nature of a microbial pathogenesis of sarcoidosis. Some groups postulate sarcoidosis is caused by an active viable replicating infection while other groups contend there is no clinical, pathologic, or microbiologic evidence for such a pathogenic mechanism. The authors posit a novel hypothesis that proposes that sarcoidosis is triggered by a hyperimmune Th1 response to pathogenic microbial and tissue antigens associated with the aberrant aggregation of serum amyloid A within granulomas, which promotes progressive chronic granulomatous inflammation in the absence of ongoing infection.

Publication types

  • Review

MeSH terms

  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Expression Regulation
  • Gene-Environment Interaction
  • Granuloma / diagnosis*
  • Granuloma / genetics
  • Granuloma / immunology
  • Granuloma / pathology
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Lymphocyte Activation
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • Propionibacterium acnes / immunology
  • Propionibacterium acnes / pathogenicity
  • Sarcoidosis / diagnosis*
  • Sarcoidosis / genetics
  • Sarcoidosis / immunology
  • Sarcoidosis / pathology
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / immunology
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology


  • Cytokines
  • HLA Antigens
  • Serum Amyloid A Protein
  • Toll-Like Receptors