Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis

Ramos-Casals, Manuel; Retamozo, Soledad; Sisó‐Almirall, Antoni; Pérez-Álvarez, R.; Pallarés, L; Brito-Zerón, Pilar

doi:10.1080/1744666x.2019.1568240

Cited by 84 publications

(71 citation statements)

References 133 publications

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“…Various biomarkers, including, serological biomarkers, bronchoalveolar lavage (BAL) biomarkers, and exhaled breath biomarkers, have been proposed numerous studies, but all have been shown to have limited applicability. Serological biomarkers should be the area of most focus for researchers moving forward as these are the least invasive and most accessible [128]. Although higher serum angiotesin converting enzyme (SACE) and BAL lymphocyte ratios are widely discussed, their utility is limited as these are not specific to sarcoidosis.…”

Section: Biomarkers For Sarcoidosismentioning

confidence: 99%

Sarcoidosis: Causes, Diagnosis, Clinical Features, and Treatments

Jain

Yadav

Puranik

et al. 2020

JCM

127

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Sarcoidosis is a multisystem granulomatous disease with nonspecific clinical manifestations that commonly affects the pulmonary system and other organs including the eyes, skin, liver, spleen, and lymph nodes. Sarcoidosis usually presents with persistent dry cough, eye and skin manifestations, weight loss, fatigue, night sweats, and erythema nodosum. Sarcoidosis is not influenced by sex or age, although it is more common in adults (< 50 years) of African-American or Scandinavians decent. Diagnosis can be difficult because of nonspecific symptoms and can only be verified following histopathological examination. Various factors, including infection, genetic predisposition, and environmental factors, are involved in the pathology of sarcoidosis. Exposures to insecticides, herbicides, bioaerosols, and agricultural employment are also associated with an increased risk for sarcoidosis. Due to its unknown etiology, early diagnosis and detection are difficult; however, the advent of advanced technologies, such as endobronchial ultrasound-guided biopsy, high-resolution computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography has improved our ability to reliably diagnose this condition and accurately forecast its prognosis. This review discusses the causes and clinical features of sarcoidosis, and the improvements made in its prognosis, therapeutic management, and the recent discovery of potential biomarkers associated with the diagnostic assay used for sarcoidosis confirmation.

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Section: Biomarkers For Sarcoidosismentioning

confidence: 99%

Sarcoidosis: Causes, Diagnosis, Clinical Features, and Treatments

Jain

Yadav

Puranik

et al. 2020

JCM

127

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“…The diagnostic trajectory of sarcoidosis is long and complicated; it requires invasive methods like bronchoalveolar lavage and evidence of granuloma in lung or other tissue through a biopsy ( 6 , 7 ). The diagnosis of sarcoidosis is then established by excluding other diseases with similar clinical or histopathological features ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Biomarkers in the Diagnosis and Prognosis of Sarcoidosis: Current Use and Future Prospects

et al. 2020

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Sarcoidosis is a heterogeneous disease in terms of presentation, duration, and severity. Due to this heterogeneity, it is difficult to align treatment decisions. Biomarkers have proved to be useful for the diagnosis and prognosis of many diseases, and over the years, many biomarkers have been proposed to facilitate diagnosis, prognosis, and treatment decisions. Unfortunately, the ideal biomarker for sarcoidosis has not yet been discovered. The most commonly used biomarkers are serum and bronchoalveolar lavage biomarkers, but these lack the necessary specificity and sensitivity. In sarcoidosis, therefore, a combination of these biomarkers is often used to establish a proper diagnosis or detect possible progression. Other potential biomarkers include imaging tools and cell signaling pathways. Fluor-18-deoxyglucose positron emission tomography and high-resolution computed tomography have been proven to be more sensitive for the diagnosis and prognosis of both pulmonary and cardiac sarcoidosis than the serum biomarkers ACE and sIL-2R. There is an upcoming role for exploration of signaling pathways in sarcoidosis pathogenesis. The JAK/STAT and mTOR pathways in particular have been investigated because of their role in granuloma formation. The activation of these signaling pathways also proved to be a specific biomarker for the prognosis of sarcoidosis. Furthermore, both imaging and cell signaling biomarkers also enable patients who might benefit from a particular type of treatment to be distinguished from those who will not. In conclusion, the diagnostic and prognostic path of sarcoidosis involves many different types of existing and new biomarker. Research addressing biomarkers and disease pathology is ongoing in order to find the ideal sensitive and specific biomarker for this disease.

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“…Taken together, no serological biomarker has so far proven ideal and in this setting we believe that CD4+ Vα2.3+ T-cells could provide additional valuable information in diagnosing and in some cases monitoring sarcoidosis. The Va2.3+ cells could perhaps be a component in the future of suggested multi-assays as proposed by Ramos-Casals et al [20]. A weakness of the present study is the composition of the controls.…”

Section: Discussionmentioning

confidence: 71%

Lung CD4+ Vα2.3+ T-cells in sarcoidosis cohorts with Löfgren’s syndrome

et al. 2020

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Background: Sarcoidosis is diagnosed by a combination of typical clinical and radiological findings together with biopsy proof of non-caseating epithelioid cell granulomas in affected tissues and/or the cell distribution in bronchoalveolar lavage fluid (BALF). We aimed at investigating the usefulness of measuring the proportion of T-cell receptor (TCR) CD4+ Vα2.3+ T-cells in BALF as an additive marker to CD4/CD8-ratio to confirm the diagnosis. Methods: From a register consisting of 749 sarcoidosis patients [Löfgren's syndrome (LS) n = 274, non-LS n = 475] with information on Vα2.3+ T-cells, an expansion of CD4+ Vα2.3+ T-cells (CD4+ Vα2.3+ T cells > 10.5% in BALF) was seen in 268 (36%). Controls were healthy volunteers (n = 69) and patients with other pulmonary conditions (n = 39), investigated because of suspicion of sarcoidosis. Results: A proportion of CD4+ Vα2.3+ T-cells in BALF > 10.5% was highly specific for sarcoidosis, with a specificity of 97% and with a sensitivity of 36% (p < 0.0001). Receiver operating characteristic (ROC) curves show that testing for CD4+ Vα2.3+ T-cells in BALF was a more useable test in individuals with LS [area under the curve (AUC) 0.82, p < 0.0001] compared to the whole patient group (AUC 0.64, p < 0.0001). Conclusion: In this study, we show that an increased proportion of CD4+ Vα2.3+ T-cells in BALF is highly specific for sarcoidosis. This suggests that this T-cell subset could be used as an additional tool to the CD4/CD8-ratio to support the sarcoidosis diagnosis, particularly in patients with LS but also in patients with non-LS.

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Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis

Cited by 84 publications

References 133 publications

Sarcoidosis: Causes, Diagnosis, Clinical Features, and Treatments

Sarcoidosis: Causes, Diagnosis, Clinical Features, and Treatments

Biomarkers in the Diagnosis and Prognosis of Sarcoidosis: Current Use and Future Prospects

Lung CD4+ Vα2.3+ T-cells in sarcoidosis cohorts with Löfgren’s syndrome

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