Eur Respir J 2019 Apr 18. Epub 2019 Apr 18.
Respiratory Medicine Unit, Department of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
Despite over a century of research, the causative agent(s) in sarcoidosis, a heterogeneous granulomatous disorder mainly affecting the lungs, remain elusive. Following identification of genetic factors underlying different clinical phenotypes, increased understanding of CD4 T-cell immunology, which is believed to be central to sarcoid pathogenesis, as well as the role of B-cells and other cells bridging innate and adaptive immunity, is now contributing to novel insights into the mechanistic pathways influencing disease resolution or chronicity. Hopefully, new perspectives and state-of-the-art technology may help to shed light on the still-elusive enigma of sarcoid aetiology. This perspective article highlights a number of recent advances in the search for antigenic targets in sarcoidosis, as well as the main arguments for sarcoidosis as a spectrum of autoimmune conditions, either as a result of an external (microbial) trigger and/or due to defective control mechanisms regulating the balance between T-cell activation and inhibition.