Challenges of Sarcoidosis and Its Management

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 385(11), P. 1018 - 1032

Published: Sept. 8, 2021

Sarcoidosis is a lung disease of unknown cause characterized by noncaseating granulomas; the heart and nervous system may also be involved. It often misdiagnosed; tissue biopsy needed for definitive diagnosis. Glucocorticoids are recommended as initial treatment, when needed, but not long-term care.

Language: Английский

---

Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 7, 2023

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune cytokine that belongs to the TNF superfamily of receptor ligands. The exists as either transmembrane or soluble molecule, and targets two distinct receptors, TNF-α 1 (TNFR1) 2 (TNFR2), which activate different signaling cascades downstream genes. cellular responses depend on its molecular form, targeted receptor, concentration levels. plays multifaceted role in normal physiology highly relevant human health disease. In central nervous system (CNS), this regulates homeostatic functions, such neurogenesis, myelination, blood-brain barrier permeability synaptic plasticity. However, it can also potentiate neuronal excitotoxicity CNS inflammation. pleiotropism various roles CNS, whether deleterious, only emphasizes functional complexity cytokine. Anti-TNF-α therapy has demonstrated effectiveness treating autoimmune inflammatory diseases emerged significant treatment option for diseases. Nevertheless, crucial recognize effects therapeutic target are diverse complex. Contrary initial expectations, anti-TNF-α been found have detrimental multiple sclerosis. This article focuses describing roles, both physiological pathological, CNS. Additionally, discusses specific disease processes dependent regulated by rationale use target.

Language: Английский

---

Single-cell and spatial transcriptomics reveal aberrant lymphoid developmental programs driving granuloma formation

Immunity, Journal Year: 2023, Volume and Issue: 56(2), P. 289 - 306.e7

Published: Feb. 1, 2023

Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on from patients with sarcoidosis bioinformatically reconstructed the underlying gene regulatory networks. We discovered an stimulatory environment repurposes transcriptional programs associated organ development. Granuloma formation followed characteristic patterns involved genes linked immunometabolism, cytokine chemokine signaling, extracellular matrix remodeling. Three cell types emerged as key players formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, fibroblasts inflammatory tissue-remodeling phenotypes. Pharmacological inhibition one identified processes attenuated a mouse model. show human adopt aspects normal development aberrant combinations, indicating constitute

Language: Английский

---

Cutaneous Sarcoidosis

Dermatologic Clinics, Journal Year: 2023, Volume and Issue: 41(3), P. 455 - 470

Published: April 5, 2023

Language: Английский

---

GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 12, 2025

Abstract Sarcoidosis is a complex inflammatory disease with strong genetic component. Here, we perform genome-wide association study in 9755 sarcoidosis cases to identify risk loci and map associated genes. We then use transcriptome-wide studies enrichment analyses explore pathways involved Mendelian randomization examine associations modifiable factors circulating biomarkers. 28 genomic sarcoidosis, the C1orf141-IL23R locus showing largest effect size. observe gene expression patterns related spleen, whole blood, lung, highlight 75 tissue-specific genes through studies. Furthermore, analysis establish key roles for T cell activation, leukocyte adhesion, cytokine production sarcoidosis. Additionally, find between genetically predicted body mass index, interleukin-23 receptor, eight proteins.

Language: Английский

---

AWMF mold guideline “Medical clinical diagnostics for indoor mold exposure” – Update 2023 AWMF Register No. 161/001

Allergologie select, Journal Year: 2024, Volume and Issue: 8(01), P. 90 - 198

Published: Jan. 1, 2024

None.

---

Immunopathophysiology and clinical impact of uveitis in inflammatory rheumatic diseases: An update

European Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 51(8)

Published: April 14, 2021

Uveitis is one of the most frequent ophthalmologic manifestations in rheumatology. Uveal inflammation can underlie a systemic inflammatory rheumatic disease (SIRD) approximately 30% cases with significant burden on quality life since it represents cause blindness up to 20% Western countries.In this review, we provide comprehensive overview pathophysiology uveitis associated SIRDs. According our literature survey epidemiology among SIRDs, spondyloarthritides, Behçet's and sarcoidosis get major impact.In uveitis, key players are highly polarized Th1 Th17 lymphocytes, natural killer T cells γδ cells. All contribute great destructive environment serious visual damage resulting from involvement posterior segment eye. In contrast, spondyloarthritides-related derives complex interaction between genetic background extra-ocular mediators originating enthesitis, arthritis, psoriatic lesions microbiome pro-inflammatory alterations. such conditions, immune infiltration CD4+ cells, along cytokines, TNF-α all, leads intraocular inflammation. Lastly, granuloma formation primary hallmark lesion sarcoid uveitis. This suggests profound link innate system that mainly recruits activated macrophages adaptive involving by Th1, Th17.1 cells.Awareness rheumatologists potential severe ocular generates new insights into targeted therapeutic approaches personalized treatments for each patient.

Language: Английский

---

Immunohistochemical Detection of Potential Microbial Antigens in Granulomas in the Diagnosis of Sarcoidosis

Journal of Clinical Medicine, Journal Year: 2021, Volume and Issue: 10(5), P. 983 - 983

Published: March 2, 2021

Sarcoidosis may have more than a single causative agent, including infectious and non-infectious agents. Among the potential causes of sarcoidosis, Mycobacterium tuberculosis Propionibacterium acnes are most likely microorganisms. Potential latent infection by both microorganisms complicates findings molecular immunologic studies. Immune responses to agents sarcoidosis should be considered together with detected in sarcoid granulomas, because reactivities reflect current past infection, unrelated cause granuloma formation. Histopathologic data readily support P. as compared M. tuberculosis, suggesting that normally symbiotic leads formation some predisposed individuals Th1 hypersensitivity against intracellular proliferation acnes, which triggered certain host or drug-induced conditions. Detection bacterial nucleic acids granulomas does not necessarily indicate co-localization proteins granulomas. In histopathologic diagnosis tuberculosis-associated acnes-associated will possibly differentiated patients immunohistochemistry appropriate antibodies specifically react mycobacterial propionibacterial antigens, respectively, for each etiology-based antimicrobial intervention sarcoidosis.

Language: Английский

---

Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: unknown

Published: June 15, 2021

Tuberculosis (TB) is a persistent global pandemic, and standard treatment for it has not changed 30 years. Mycobacterium tuberculosis (Mtb) undergone prolonged coevolution with humans, patients can control Mtb even after extensive infection, demonstrating the fine balance between protective pathological host responses within infected granulomas. We hypothesized that whole transcriptome analysis of human TB granulomas isolated by laser capture microdissection could identify therapeutic targets, comparison noninfectious granulomatous disease, sarcoidosis, would disease-specific mechanisms. Bioinformatic RNAseq data identified numerous shared pathways sarcoidosis lymph nodes, also specific clusters results from dysregulated inflammatory immune response. To translate these insights, we compared 3 primary cell culture models at level demonstrated 3D collagen granuloma model most closely reflected disease. investigated signaling disease 12 intracellular enzymes as potential targets. Sphingosine kinase 1 inhibition controlled growth, concurrently reducing pH in monocytes suppressing mediator secretion. Immunohistochemical staining confirmed sphingosine expressed lung granulomas, therefore represents target to improve outcomes.

Language: Английский

---

Medizinisch klinische Diagnostik bei Schimmelpilzexposition in Innenräumen – Update 2023 (AWMF-Register-Nr. 161/001)

Pneumologie, Journal Year: 2024, Volume and Issue: 78(10), P. 693 - 784

Published: Feb. 9, 2024

This article is an abridged version of the updated AWMF mould guideline "Medical clinical diagnostics in case indoor exposure - Update 2023", presented July 2023 by German Society Hygiene, Environmental Medicine and Preventive (Gesellschaft für Umweltmedizin und Präventivmedizin, GHUP), collaboration with Austrian scientific medical societies, experts. Indoor growth a potential health risk, even if quantitative and/or causal relationship between occurrence individual species problems has yet to be established. There no evidence for moisture/mould damage human diseases, mainly because ubiquitous presence fungi hitherto inadequate diagnostic methods. Sufficient association following effects been established for: allergic respiratory rhinitis, rhino-conjunctivitis, bronchopulmonary aspergillosis (ABPA), other mycosis (ABPM), aspergilloma, Aspergillus bronchitis, asthma (manifestation, progression, exacerbation), bronchitis (acute, chronic), community-acquired pneumonia, hypersensitivity pneumonitis (HP; extrinsic alveolitis (EEA)), invasive Aspergillosis, mycoses, organic dust toxic syndrome (ODTS) [workplace exposure], promotion infections, pulmonary (subacute, rhinosinusitis chronically invasive, or granulomatous, allergic). In this context sensitizing moulds obviously low compared environmental allergens. Recent studies show comparatively sensitization prevalence 3-22,5 % general population across Europe. Limited suspected exist respect atopic eczema (atopic dermatitis, neurodermatitis; manifestation), chronic obstructive disease (COPD), mood disorders, mucous membrane irritation (MMI), odor effects, sarcoidosis. (iv) Inadequate insufficient acute idiopathic hemorrhage infants, airborne transmitted mycotoxicosis, arthritis, autoimmune cancer, fatigue (CFS), endocrinopathies, gastrointestinal multiple chemical sensitivity (MCS), sclerosis, neuropsychological neurotoxic renal reproductive rheumatism, sick building (SBS), sudden infant death syndrome, teratogenicity, thyroid urticaria.The risk infection posed regularly occurring indoors healthy persons; most are group 1 few 2 (

Language: Английский

---