Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Beijer, Els; Veltkamp, Marcel; Meek, Bob; Möller, David R.

doi:10.1055/s-0037-1603087

Cited by 26 publications

(5 citation statements)

References 142 publications

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“…A multitude of immunological debates suggest that the insu cient removal of viral particles, along with diverse immunode ciencies, could play a role in sarcoidosis disease [34]. Thus, our study supports previous research showing sarcoidosis as an immune-validated disease with a complex disease pathogenesis [35], underscoring the signi cance of alterations in receptor genes in its development.…”

Section: Discussionsupporting

confidence: 89%

Identification and Validation of Hub Differential Genes in Pulmonary Sarcoidosis

Yao,

Min,

Zhao

et al. 2024

Preprint

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Peripheral blood measurement based on tissue biopsy confirmation may facilitate the discovery of new diagnostic and therapeutic biological markers for pulmonary sarcoidosis. The gene expression levels of mediastinal lymph nodes were estimated by RNA immunoprecipitation sequencing. Biopsy samples from three pulmonary sarcoidosis patients were retrieved by mediastinoscopy or thoracoscopy surgery in Shanghai Pulmonary Hospital and three biopsy samples from patients with in situ lung carcinoma were utilized as normal controls. The public transcriptomic dataset GSE34608 was leveraged, in which whole blood gene expression from 18 pulmonary sarcoidosis patients and 18 healthy controls was available. The genes changing in the same direction in two kinds of samples were recognized as common differentially expressed genes (DEGs). Bioinformatics analysis was applied to identify the hub DEGs and to explore the potential mechanism. Ultimately, the validation of hub DEGs’ expression levels was conducted in PBMC samples from 9 patients diagnosed with pulmonary sarcoidosis and a control group consisting of 7 healthy individuals. A total of 138 common DEGs were screened from mediastinal lymph nodes and peripheral whole blood. Among them, 6 hub DEGs including CTSS, CYBB, FPR2, MNDA, TLR1 and TLR8 were identified by PPI network and further verified by qRT-PCR using PBMC samples. The most significant functional pathways were immune response, inflammatory response, plasma membrane and extracellular exosome, with 6 hub genes distributing along these pathways. In conclusion, CTSS, CYBB, FPR2, MNDA, TLR1, and TLR8 could be conducive to improving the diagnostic process and understanding the underlying mechanisms of pulmonary sarcoidosis.

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Section: Discussionsupporting

confidence: 89%

Identification and Validation of Hub Differential Genes in Pulmonary Sarcoidosis

Yao,

Min,

Zhao

et al. 2024

Preprint

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“…Elevated levels of SAA have also been found in sarcoidosis, and appear to correlate with a decline in lung function ( 42 ). Sarcoidosis has been suggested as a heterogeneous disease, with multiple potential triggers such as metals or micro-organisms ( 43 ). If in the future patients could be distinguished based on possible triggers, it would be interesting to study SAA as a biomarker in a specific subgroup of sarcoidosis patients with micro-organisms such as mycobacteria or propionic bacteria as suspected triggers ( 44 ).…”

Section: Serum Biomarkersmentioning

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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“…У женщин при СЛ отмечаются более выраженные клинические проявления заболевания, чем у мужчин, что характерно для многих заболеваний аутоиммунного происхождения [73]. При этом летальность составляет от 0,3 до 7,4 %, и частыми причинами смерти служат последствия сердечной, дыхательной, почечной недостаточности, тяжелой сопутствующей онкопатологии [6,60]. Возможна гибель пациентов и от присоединения (или активизации латентной) инфекции, не только неспецифической, но и ТЛ, ВИЧ-инфекции, лепры -в первую очередь, на фоне применяемой при саркоидозе иммуносупрессивной терапии [8,83].…”

Section: к линико-патофизиологические особенности с аркоидозаunclassified

Comparative aetio-epidemiological analysis of lung tuberculosis versus sarcoidosis: classical and new concepts

et al. 2020

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The review presents data on two similar granulomatous inflammatory diseases: tuberculosis and sarcoidosis of the lungs, which together cover about 5% of all pulmonary pathology, albeit occur with different incidence (20 : 1). Despite the established aetiology of tuberculosis, the disease has not disappeared and nowadays has even acquired a new urgency: It is getting out of control due to growing poverty, the comorbidity with HIV infection, increasing cases of drug resistance of Mycobacteria, insufficient effectiveness and the growing costs of its treatment. Against the background of the expansion of anthropogenic influences and other environmental impacts on the immune system, the incidence of lung sarcoidosis is also increasing, while patients are initially often misdiagnosed with tuberculosis, with resulting unjustified anti-tuberculosis chemotherapy, leading to chronization of the disease with frequent relapses and, accordingly, to an increase in disability and mortality rates. In recent years, clinical manifestations of sarcoidosis due to a variety of trigger aetiological factors with adjuvant-like action (from Mycobacteria to xenobiotics) are considered by a number of authors as a variant of autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA). The article emphasizes the similarity of two granulomatous inflammatory diseases and the concept of two variants of the bodys response to similar or even identical aetiological factors within different human reactivity (possibly on a different mosaic/permissive background). In brief the newest data on experimental models of sarcoidosis are reviewed as well as the role of autophagy disorders and opposite macrophageal polarization in tuberculosis versus sarcoidosis. Authors coined the original hypothesis of the possible therapeutic effectiveness of Rapamycin in sarcoidosis and for the first time posed a question of equivocal character of comorbidity between these granulomatoses and COVID-19 infection.

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Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Cited by 26 publications

References 142 publications

Identification and Validation of Hub Differential Genes in Pulmonary Sarcoidosis

Identification and Validation of Hub Differential Genes in Pulmonary Sarcoidosis

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

Comparative aetio-epidemiological analysis of lung tuberculosis versus sarcoidosis: classical and new concepts

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