Sarcoidosis: Immunopathogenesis and Immunological Markers

Sarcoidosis is a multisystem granulomatous disorder invariably affecting the lungs. It is a disease with noteworthy variations in clinical manifestation and disease outcome and has been described as an “immune paradox” with peripheral anergy despite exaggerated inflammation at disease sites. Despite extensive research, sarcoidosis remains a disease with undetermined aetiology. Current evidence supports the notion that the immune response in sarcoidosis is driven by a putative antigen in a genetically susceptible individual. Unfortunately, there currently exists no reliable biomarker to delineate the disease severity and prognosis. As such, the diagnosis of sarcoidosis remains a vexing clinical challenge. In this review, we outline the immunological features of sarcoidosis, discuss the evidence for and against various candidate etiological agents (infective and noninfective), describe the exhaled breath condensate, a novel method of identifying immunological biomarkers, and suggest other possible immunological biomarkers to better characterise the immunopathogenesis of sarcoidosis. 1. Introduction Sarcoidosis is a multisystem, inflammatory disorder of obscure aetiology. Its defining histopathology is the existence of noncaseating epithelioid granulomas with accompanying mononuclear cell infiltration and microarchitecture destruction [1, 2]. Although sarcoidosis involves the lungs in >90% of cases, it also affects the heart, skin, eye, and central nervous system [3]. This accounts for its heterogeneous clinical manifestation which ranges from having no symptoms to severe consequences, namely respiratory insufficiency, cardiac death, neurological disease, and blindness [4]. Sarcoidosis has been reported in all ethnic and racial groups with the majority of studies recording a peak incidence of 20–39 years of age for both males and females and a bimodal distribution whereby women have another peak incidence at 65–69 [4]. Disease remission occurs in as many as two-thirds of patients, usually in the first 3 years after diagnosis. Other patients have chronic unremitting sarcoidosis which may subsequently lead to lung fibrosis [1]. The erratic clinical course has impelled research into biomarkers that could delineate disease severity and outcome [5]. To date, there exist no reliable and practical biomarkers for sarcoidosis [6]. Moreover, despite earnest research efforts, the immunopathogenesis and aetiology underpinning sarcoidosis remains elusive [3]. This review outlines the current understanding of sarcoidosis, with reference to ex vivo lymphocyte stimulation