New concepts in the pathogenesis of sarcoidosis

ABSTRACT

Introduction: The pathogenesis of sarcoidosis is not yet completely understood, although in recent years our knowledge has made considerable progress.

Areas covered: This review aims to highlight the latest findings, identified from PubMed, EMBASE, and Web of Science, on the pathogenetic mechanisms of sarcoidosis, considering the studies on potential environmental antigens, genetic background and host immune responses. Particular emphasis has been on recent studies on antigens, as it now seems clear that it is not a single, but various antigens of microbial and non-microbial origin that share the ability to induce the series of immune-inflammatory events that lead to granuloma formation, activating host genetically influenced immune responses that involve innate and even more adaptive immunity. The dysregulation of Th17, Th17.1 cells and Tregs, and their role in the resolution and maintenance of granulomatous inflammation has been reported.

Expert opinion: The considerable amount of data that has been accumulated on sarcoidosis pathogenesis will have to be carefully interpreted, particularly to discover which pathways lead to severe forms with organ damage. There is an urgent need for a panel of biomarkers indicating the involvement of the various pathways, to be used for better characterizing patient phenotypes and developing targeted therapies.

KEYWORDS:

• Sarcoidosis
• pathogenesis
• granuloma
• lymphocytes
• macrophages

Article highlights

• In sarcoidosis, various enviromental antigens of microbial and non-microbial origin induce in the host immune-inflammatory responses that lead to granuloma formation.

• Host genetically influenced immune responses involve innate and even more adaptive immunity.

• The Th17, Th17.1 and Treg cells dysregulation has a central role in resolution and maintenance of granulomatous inflammation and these cells balance is crucial.

• Serum amyloid A (SAA), that participates in promoting maintenance of chronic granulomatous inflammation, as well as self-antigens, such as vimentin, with potential autoimmunity involvement, are of interest and need further investigation.

• A panel of biomarkers indicating the involvement of the various pathways is needed for a better characterization of  patient phenotype and development of targeted therapies.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.