Sarcoidosis: Immunopathogenesis and Immunological Markers

Abstract

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.

Induction of Pulmonary Granuloma Formation byPropionibacterium acnesIs Regulated by MyD88 and Nox2

“…The cause of sarcoidosis is a complex immune paradox consisting of a localized hyperinflammatory environment coupled with peripheral anergy (39). Despite the evidence that granulomas form in response to persistent antigen stimulation (40), and that this antigen is likely bacterial in origin (10), most work on sarcoidosis has centered on T cells and, to a lesser extent, tissue macrophages and dendritic cells (41).…”

Sarcoidosis

“…15 Studies suggest that development of sarcoidosis involves an interplay between extrinsic antigens, genetic factors, and immune responses. 16,17 The regulation of immune mechanisms is more complex and extensive than can be discussed in this article, 18 but researchers have suggested that poorly degraded antigen is engulfed by antigen-presenting cells (APCs) and displayed on the APCs' major histocompatibility complex (MHC). 10,18 A CD41 T-cell receptor attaches to this antigen-MHC complex and becomes activated.…”

“…16,17 The regulation of immune mechanisms is more complex and extensive than can be discussed in this article, 18 but researchers have suggested that poorly degraded antigen is engulfed by antigen-presenting cells (APCs) and displayed on the APCs' major histocompatibility complex (MHC). 10,18 A CD41 T-cell receptor attaches to this antigen-MHC complex and becomes activated. The result is a release of cytokines, including interleukin (IL)-2, which induce clonal proliferation of activated, strongly Th1 polarized T-helper cells that secrete proinflammatory cytokines, such as IL-2, IL-12, and IL-18 (interferon-gamma-inducing factor), which facilitate granuloma formation.…”

“…Further release of cytokines and chemokines causes macrophage aggregation into granulomas. 10,18 Granulomas are composed of epithelioid cells, mononuclear cells, and CD41 T cells with a few CD81 T cells around the periphery. Recently, serum amyloid A was found to be present in granulomas and to amplify Th1 responses by interacting with Toll-like receptor 2.…”

Epidemiology of Sarcoidosis in the Russian Federation

“…С аркоидоз -системная патология иммунной системы, характеризующаяся образованием эпителиоидно-клеточных неказеифицирующихся гранулем и иммунным парадоксом, проявляю-щимся избыточной клеточной реакцией в местах проявления болезни при периферической анергии [1]. Однако выявление саркоидной гранулемы вне связи с конкретной клинической ситуацией не позво-ляет установить диагноз «саркоидоз».…”