Key Players and Biomarkers of the Adaptive Immune System in the Pathogenesis of Sarcoidosis

Abstract

Sarcoidosis is a systemic inflammatory disease characterized by development of granulomas in the affected organs. Sarcoidosis is often a diagnosis of exclusion, and traditionally used tests for sarcoidosis demonstrate low sensitivity and specificity. We propose that accuracy of diagnosis can be improved if biomarkers of altered lymphocyte populations and levels of signaling molecules involved in disease pathogenesis are measured for patterns suggestive of sarcoidosis. These distinctive biomarkers can also be used to determine disease progression, predict prognosis, and make treatment decisions. Many subsets of T lymphocytes, including CD8+ T-cells and regulatory T-cells, have been shown to be dysfunctional in sarcoidosis, and the predominant CD4+ T helper cell subset in granulomas appears to be a strong indicator of disease phenotype and outcome. Studies of altered B cell populations, B cell signaling molecules, and immune complexes in sarcoidosis patients reveal promising biomarkers as well as possible explanations of disease etiology. Furthermore, examined biomarkers raise questions about new treatment methods and sarcoidosis antigens.

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“…The Tregs have also been reported in the mutations of BTNL2 (Butyrophilin like 2) and ANXA11 (Annexin A11), leading to the development of gene products with anti-inflammatory and immune regulatory properties. These lead to the development of an imbalance between regulatory T cells and Th17, responsible for autoimmune diseases 12 . gene expression of Tbx21, finally enhances IFNγ gene transcription competence leading to an increase in the IFN-γ production.…”

“…The severity of inflammation can be identified by this scan by the use of a radioactive material Ffluorodeoxyglucose (iv) 12,24 .…”

“…A retrospective study reported that azathioprine and methotrexate are equally efficient, but azathioprine appeared to have more side effects 34 . Mycophenolate mofetil and leflunomide are other second-line alternatives 12 .…”

BATF2 and PDK4 As Diagnostic Molecular Markers of Sarcoidosis and Their Relationship With Immune Infiltration

“…They are tightly packed cell clusters, forming the primary core of multinucleated giant cells, epithelioid histiocytes, and macrophages enclosed in a lymphocyte collar [12]. Although CD4+ T-cells are majorly localized within the lymphocyte collar, a few B cells, CD8+ Tcells, broblasts, and plasma cells are present, too [13]. CD4+ T lymphocytes are crucial in sarcoidosis progression as they recruit leukocytes, eventually generating granulomas, whose interaction with B cells stimulates the production of antibodies [14].…”

Biomarkers in Rare Diseases

“…From these findings, the authors concluded that hTERT is a relevant antigen in HPV-driven SCCA disease and that the levels of M-MDSC influence TH1-adaptive immune responses and patient survival. In researching biomarkers of sarcoidosis, an inflammatory disease of unknown origin, Zhou and Arce provide an important review of the key players and biomarkers of the adaptive immune system in the pathogenesis of this disorder [ 9 ]. The authors highlight that there is no specific biomarker for sarcoidosis and that the majority of biomarkers examined to date remain unvalidated in the clinical setting or are insufficiently specific or sensitive for use in isolation for the purpose of clinical-decision making.…”