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Semin Respir Crit Care Med
DOI: 10.1055/a-2741-2030
Review Article

Biomarkers in Sarcoidosis: From Traditional Markers to Precision Medicine

Authors

  • Maria Belen Pascual

    1   Interstitial Lung Disease Program, Pneumology Department, Respiratory Clinical Institute, Hospital Clinic, Barcelona, Spain

  • Juan Jose Zapata-Huizi

    1   Interstitial Lung Disease Program, Pneumology Department, Respiratory Clinical Institute, Hospital Clinic, Barcelona, Spain

  • Daniel Ramos

    2   Instituto Nacional del Tórax, Santiago, Chile

  • Joel Francesqui

    3   Institut de Recerca Sant Pau (IR SANT PAU), Respiratory Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

  • Xavier Alsina-Restoy

    1   Interstitial Lung Disease Program, Pneumology Department, Respiratory Clinical Institute, Hospital Clinic, Barcelona, Spain
    4   CIBER of Respiratory Diseases, Barcelona, Spain
    5   Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

  • Fernanda Hernández-González

    1   Interstitial Lung Disease Program, Pneumology Department, Respiratory Clinical Institute, Hospital Clinic, Barcelona, Spain
    4   CIBER of Respiratory Diseases, Barcelona, Spain
    5   Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

  • Jacobo Sellares

    1   Interstitial Lung Disease Program, Pneumology Department, Respiratory Clinical Institute, Hospital Clinic, Barcelona, Spain
    4   CIBER of Respiratory Diseases, Barcelona, Spain
    5   Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
    6   Facultat de Medicina, University of Vic (UVIC), Barcelona, Spain

Funding Information The study was financed by a Project (project no.: PI23/00924), funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union Fundació La Marató de TV3 (grant no.: 61/C/2025) for respiratory diseases research, SEPAR, SOCAP, FUCAP, and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS).
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Abstract

Sarcoidosis remains a diagnostic and therapeutic challenge due to its heterogeneous clinical presentation and lack of pathognomonic features. Despite five decades of biomarker research, no single marker has achieved sufficient accuracy for a standalone diagnosis. Traditional biomarkers retain clinical utility when used strategically: High-sensitivity markers (soluble interleukin-2 receptor [sIL-2R], serum amyloid A [SAA], chitotriosidase) excel at confirming disease, while high-specificity markers (lysozyme) better exclude sarcoidosis. Chitotriosidase has emerged as superior to angiotensin-converting enzyme (ACE) for disease monitoring, and sIL-2R remains invaluable for detecting extrapulmonary involvement. However, their limitations necessitate multibiomarker approaches tailored to specific clinical phenotypes. Recent advances address critical unmet needs. High-sensitivity troponin T provides crucial prognostic information in cardiac sarcoidosis, with levels >14 ng/L predicting adverse outcomes. Novel fibrosis markers, including alveolar nitric oxide, heat shock protein 90α (HSP90α), and advanced Krebs von den Lungen-6 (KL-6) measurement, enable better assessment of disease progression. Prediagnostic inflammatory proteins elevated years before clinical manifestation suggest opportunities for early intervention. Revolutionary omics technologies are transforming biomarker discovery. Extracellular vesicle proteomics identifies treatment-responsive signatures, retrotrans-genomics reveals viral element activation in pathogenesis, and Mendelian randomization distinguishes causal from associative proteins. Integration of multiomics data through machine learning algorithms promises personalized diagnostic and therapeutic strategies. The future of sarcoidosis management lies in intelligent biomarker integration rather than reliance on single tests. Success will be measured by improved patient outcomes through earlier diagnosis, accurate risk stratification, and personalized treatment selection. This paradigm shift from empirical to precision medicine requires continued collaboration between researchers, clinicians, and patients to translate biomarker discoveries into clinical practice.

Keywords

sarcoidosis - biomarkers - angiotensin-converting enzyme - chitotriosidase - cardiac sarcoidosis - precision medicine


Publication History

Received: 25 July 2025

Accepted: 06 November 2025

Accepted Manuscript online:
10 November 2025

Article published online:
12 December 2025

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