RESUMEN
Although the role of T lymphocytes in sarcoidosis (SA) and lung cancer (LC) is quite well reported, the occurrence of B cells in disease microenvironments may suggest their potential role as natural modifiers of the immune response. The aim of this study was to investigate the B-cell profile and lymphocyte-related hematological parameters between patients with SA, LC and healthy controls (HCs). The cells were assessed by flow cytometry and a hematological analyzer in peripheral blood (PB) and material from lymph nodes (LNs) obtained by the EBUS/TBNA method. We showed that in SA patients, there were higher percentages of naïve B and CD21low B cells and a lower percentage of class-switched memory B cells than LC patients in LNs. We observed a higher median proportion of non-switched memory and transitional B cells in the PB of SA patients than in LC patients. We noticed the lowest median proportion of class-switched memory B cells in the PB from SA patients. LC patients had a higher percentage of RE-LYMP and AS-LYMP than SA patients. Our study presented a different profile of B-cell subpopulations in SA and LC patients, distinguishing dominant subpopulations, and showed the relocation from distant compartments of the circulation to the disease microenvironment, thus emphasizing their role.
Asunto(s)
Neoplasias Pulmonares , Sarcoidosis , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/sangre , Masculino , Femenino , Persona de Mediana Edad , Sarcoidosis/inmunología , Sarcoidosis/patología , Sarcoidosis/sangre , Microambiente Tumoral/inmunología , Subgrupos de Linfocitos B/inmunología , Adulto , Anciano , Ganglios Linfáticos/patología , Ganglios Linfáticos/inmunología , Linfocitos B/inmunología , Estudios de Casos y ControlesRESUMEN
Neurosarcoidosis, a rare granulomatous disease, causes inflammation and damage to the central nervous system (CNS). A major diagnostic challenge in neurosarcoidosis is the absence of well-defined biomarkers. The need for biopsy to make the diagnosis can lead to delays and misdiagnosis if histopathology is inaccessible or indeterminate, highlighting the need for more accessible diagnostic indicators. The current gold standard for a "definite" neurosarcoidosis diagnosis requires biopsy of CNS tissue revealing non-caseating granulomas. However, such biopsies are inherently invasive and carry associated procedural risks. Notably, angiotensin-converting enzyme (ACE), commonly associated with systemic sarcoidosis, is recognized as a poor biomarker for neurosarcoidosis due to its lack of accuracy in the context of CNS involvement. Furthermore, imaging in neurosarcoidosis, while widely utilized and important for narrowing the diagnosis, lacks specificity. Decades of research have yielded molecular and immunologic biomarkers-soluble interleukin-2 receptor (IL-2R), serum amyloid A1, the CD4/CD8 ratio, neopterin, interferon-gamma (IFN-γ), and chemokine ligand 2 (CCL2)-that hold potential for improving diagnostic accuracy. However, these biomarkers are not yet established in clinical care as they may be difficult to obtain and are derived from small studies. They also suffer from a lack of specificity against other inflammatory and infectious central nervous system diseases. New biomarkers are needed for use alongside those previously discovered to improve diagnosis of this rare disease. This review synthesizes existing literature on neurosarcoidosis biomarkers, aiming to establish a foundation for further research in this evolving field. It also consolidates information on biomarkers of systemic sarcoidosis such as IL-8 and soluble CD40L that have not yet been studied in neurosarcoidosis but hold potential as markers of CNS disease.
Asunto(s)
Biomarcadores , Enfermedades del Sistema Nervioso Central , Sarcoidosis , Sarcoidosis/líquido cefalorraquídeo , Sarcoidosis/diagnóstico , Sarcoidosis/sangre , Humanos , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/sangre , Biopsia , Peptidil-Dipeptidasa A/líquido cefalorraquídeo , Peptidil-Dipeptidasa A/sangre , Receptores de Interleucina-2/sangreRESUMEN
OBJECTIVES: Serum angiotensin-converting enzyme (ACE) is the only biomarker routinely used in the laboratory diagnostics of sarcoidosis, and ACE inhibitor (ACEi) drugs are among the most prescribed drugs worldwide. Taking ACEi can mislead medical teams by lowering ACE activity, delaying diagnosis and giving a false impression of disease activity of sarcoidosis. We aimed to develop a simple method to detect the presence of ACEi drugs in samples, to investigate the ACEi medication-caused interference and consequences in a retrospective study. METHODS: ACE activity and the level of ACE inhibition were determined for 1823 patients with suspected sarcoidosis. These values were compared with the therapeutic information at the first and follow-up visits. RESULTS: A total of 302 patients had biochemical evidence of an ACEi drug effect during diagnostic ACE activity testing. In their case, ACE activity was significantly lower (median(IQR): 4.41â¯U/L(2.93-6.72)) than in patients not taking ACEi (11.32â¯U/L(8.79-13.92), p<0.01). In 62 sarcoidosis patients, the ACEi reduced ACE activity to the reference range or below. Only in 40â¯% of the cases was the medication list recorded in the outpatient chart and only in 3 cases was low ACE activity associated with ACEi use. 67â¯% of the repeated ACE activity measurements were also performed during ACEi therapy. CONCLUSIONS: Our study revealed that the use of ACEi is common in patients with suspected sarcoidosis. The ACE activity lowering effect of ACEi drugs may escape the attention of medical teams which can lead to diagnostic errors and unnecessary tests. Nevertheless, these pitfalls can be avoided by using a method suggested by our team.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Peptidil-Dipeptidasa A , Sarcoidosis , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/diagnóstico , Sarcoidosis/sangre , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Peptidil-Dipeptidasa A/sangre , Adulto , Biomarcadores/sangreRESUMEN
The usefulness of serum angiotensin-converting enzyme (sACE) for diagnosing sarcoidosis and determining the active status of sarcoidosis has been reported with varying outcomes. On the basis of the majority of published data, we conducted a meta-analysis to calculate the overall predictive accuracy of sACE in sarcoidosis disease and the active status of sarcoidosis. The inclusion of related research listed in Web of Science, PubMed, Scopus, and other literature databases was assessed. SROC curves were generated to characterize the overall test results after data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were combined. Publication bias was identified using Deeks' funnel plot. Thirty-five publications with 8645 subjects met the inclusion criteria. The following are summary estimates of sACE diagnostic performance for sarcoidosis: sensitivity, 60% (95% confidence interval (CI), 52-68%); specificity, 93% (95% CI, 88-96%); PLR, 8.4 (95% CI, 5.3-13.3); NLR, 0.43 (95% CI, 0.36-0.52); and DOR, 19 (95% CI, 12-31). The area under the SROC curve (AUC) was 0.84 (95% CI, 0.80-0.87). Summary estimates for predicting the active status of sarcoidosis were as follows: sensitivity, 0.76 (95% CI, 0.61-0.87); specificity, 0.80 (95% CI, 0.64-0.90); PLR, 3.9 (95% CI, 2.1-7.3); NLR, 0.29 (95% CI, 0.17-0.49); and DOR, 13 (95% CI, 6-31). The AUC was 0.85 (95% CI, 0.82-0.88). There was no evidence of publication bias. Our meta-analysis suggests that measuring the sACE may assist in the diagnosis of sarcoidosis and predicting the active status of sarcoidosis, but the interpretation of the sACE results should be with caution. Future studies should validate our results.
Asunto(s)
Peptidil-Dipeptidasa A , Sarcoidosis , Humanos , Angiotensinas , Oportunidad Relativa , Sarcoidosis/sangre , Sarcoidosis/diagnóstico , Peptidil-Dipeptidasa A/sangreRESUMEN
METHODS: Cerebrospinal fluid (CSF) and plasma levels of 38 biomarkers from 20 neurosarcoidosis (NS) patients were compared to healthy controls (HC). RESULTS: In CSF, 25 biomarkers were significantly elevated compared to HC: IFNγ, TNFα, TNFß, IL-2, IL-6, IL-10, IL-12B, IL-15, IL-16, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26, CXCL8, CXCL10, TNFR2, VEGF-A, PIGF, SAA, VCAM1, and ICAM1. In plasma, 12 biomarkers were significantly elevated compared to HC: IFNγ, TNFα, CCL2, CCL3, CCL4, CCL17, CXCL10, VEGFR1, PIGF, SAA, VCAM1, and ICAM1. CONCLUSION: NS patients have profoundly elevated cytokines, chemokines, vascular angiogenesis, and vascular injury biomarkers in CSF and plasma.
Asunto(s)
Enfermedades del Sistema Nervioso Central , Quimiocinas , Citocinas , Sarcoidosis , Biomarcadores , Enfermedades del Sistema Nervioso Central/sangre , Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Humanos , Sarcoidosis/sangre , Sarcoidosis/líquido cefalorraquídeoRESUMEN
Sarcoidosis is a complex, polygenic, inflammatory granulomatous multi-organ disease of unknown cause. The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. Extracellular vesicles (EVs) play important roles in intercellular communication. We subjected serum EVs, isolated by size exclusion chromatography, from seven patients with sarcoidosis and five control subjects to non-targeted proteomics analysis. Non-targeted, label-free proteomics analysis detected 2292 proteins in serum EVs; 42 proteins were up-regulated in patients with sarcoidosis relative to control subjects; and 324 proteins were down-regulated. The protein signature of EVs from patients with sarcoidosis reflected disease characteristics such as antigen presentation and immunological disease. Candidate biomarkers were further verified by targeted proteomics analysis (selected reaction monitoring) in 46 patients and 10 control subjects. Notably, CD14 and lipopolysaccharide-binding protein (LBP) were validated by targeted proteomics analysis. Up-regulation of these proteins was further confirmed by immunoblotting, and their expression was strongly increased in macrophages of lung granulomatous lesions. Consistent with these findings, CD14 levels were increased in lipopolysaccharide-stimulated macrophages during multinucleation, concomitant with increased levels of CD14 and LBP in EVs. The area under the curve values of CD14 and LBP were 0.81 and 0.84, respectively, and further increased to 0.98 in combination with angiotensin-converting enzyme and soluble interleukin-2 receptor. These findings suggest that CD14 and LBP in serum EVs, which are associated with granulomatous pathogenesis, can improve the diagnostic accuracy in patients with sarcoidosis.
Asunto(s)
Proteínas de Fase Aguda , Vesículas Extracelulares , Receptores de Lipopolisacáridos , Sarcoidosis , Proteínas de Fase Aguda/análisis , Biomarcadores/análisis , Vesículas Extracelulares/química , Humanos , Receptores de Lipopolisacáridos/sangre , Glicoproteínas de Membrana/sangre , Proteómica/métodos , Sarcoidosis/sangre , Sarcoidosis/diagnósticoRESUMEN
OBJECTIVE: To investigate the diagnostic and staging value of serum angiotensin-converting enzyme (sACE) in sarcoidosis. METHODS: Patients with suspected sarcoidosis treated in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital from 2010 to 2020 were included. The data of sACE, erythrocyte sedimentation rate (ESR), complete blood count (CBC), lung function, bronchoalveolar lavage, and biopsy were collected. The differences between the sarcoidosis group and the nonsarcoidosis group and between different stages of sarcoidosis were compared. The receiver operating characteristic (ROC) curve analysis was used for the diagnostic test of sACE in sarcoidosis. RESULTS: A total of 84 cases with suspected sarcoidosis were included, among which 70 cases were confirmed to be sarcoidosis by biopsy. The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients (28.07 ± 14.11 U/L, P = 0.001). The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multiple system involvement was significantly higher than that in intrathoracic sarcoidosis patients (P = 0.009); the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients was 45.39 ± 22.87%, which was significantly higher than that of nonsarcoidosis patients (P < 0.001). There was no correlation between sACE and ESR (correlation coefficient = -0.167). According to ROC curve analysis, when sACE ≥ 44.0 U/L, the sensitivity of sarcoidosis diagnosis was 61.4%, the specificity was 92.9%, and the AUC was 0.819. CONCLUSION: sACE has a good specificity in the diagnosis of sarcoidosis. sACE values in patients with sarcoidosis with systemic involvement were higher than those with simple intrathoracic sarcoidosis.
Asunto(s)
Peptidil-Dipeptidasa A/sangre , Sarcoidosis/sangre , Adulto , Anciano , Biomarcadores/sangre , Sedimentación Sanguínea , Biología Computacional , Femenino , Humanos , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Estudios Prospectivos , Sarcoidosis/clasificación , Sarcoidosis/diagnósticoRESUMEN
OBJECTIVE: Blau syndrome (BS), a rare, autosomal-dominant autoinflammatory syndrome, is characterized by a clinical triad of granulomatous recurrent uveitis, dermatitis, and symmetric arthritis and associated with mutations of the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Aim of this study was to assess the efficacy of tofacitinib in Chinese paediatric patients with BS. METHODS: Tofacitinib was regularly administered to three BS patients (Patient 1, Patient 2, and Patient 3) at different dosages: 1.7 mg/day (0.11 mg/kg), 2.5 mg/day (0.12 mg/kg), and 2.5 mg/day (0.33 mg/kg). The clinical manifestations of the patients, magnetic resonance imaging results, serological diagnoses, therapeutic measures and outcomes of treatments are described in this report. RESULTS: The clinical characteristics and serological diagnoses of all BS patients were greatly improved after the administration of tofacitinib treatment. All patients reached clinical remission of polyarthritis and improvements in the erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and inflammatory cytokines. CONCLUSION: Tofacitinib, a Janus kinase (JAK) inhibitor, is a promising agent for BS patients who have unsatisfactory responses to corticosteroids, traditional disease-modifying antirheumatic drugs, and biological agents.
Asunto(s)
Artritis/tratamiento farmacológico , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Sarcoidosis/tratamiento farmacológico , Sinovitis/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Artritis/sangre , Artritis/diagnóstico , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Niño , Preescolar , Citocinas/sangre , Electrocardiografía , Estudios de Seguimiento , Humanos , Lactante , Inhibidores de las Cinasas Janus/uso terapéutico , Articulaciones/patología , Imagen por Resonancia Magnética/métodos , Masculino , Sarcoidosis/sangre , Sarcoidosis/diagnóstico , Sinovitis/sangre , Sinovitis/diagnóstico , Factores de Tiempo , Uveítis/sangre , Uveítis/diagnósticoRESUMEN
While cardiac imaging has improved the diagnosis and risk assessment for cardiac sarcoidosis (CS), treatment regimens have consisted of generalized heart failure therapies and non-specific anti-inflammatory regimens. The overall goal of this study was to perform high-sensitivity plasma profiling of specific inflammatory pathways in patients with sarcoidosis and with CS.Specific inflammatory/proteolytic cascades were upregulated in sarcoidosis patients, and certain profiles emerged for CS patients.Plasma samples were collected from patients with biopsy-confirmed sarcoidosis undergoing F-18 fluorodeoxyglucose positron emission tomography (n = 47) and compared to those of referent control subjects (n = 6). Using a high-sensitivity, automated multiplex array, cytokines, soluble cytokine receptor profiles (an index of cytokine activation), as well as matrix metalloproteinase (MMP), and endogenous MMP inhibitors (TIMPs) were examined.The plasma tumor necrosis factor (TNF) and soluble TNF receptors sCD30 and sTNFRI were increased using sarcoidosis, and sTNFRII increased in CS patients (n = 18). The soluble interleukin sIL-2R and vascular endothelial growth factor receptors (sVEGFR2 and sVEGFR3) increased to the greatest degree in CS patients. When computed as a function of referent control values, the majority of soluble cytokine receptors increased in both sarcoidosis and CS groups. Plasma MMP-9 levels increased in sarcoidosis but not in the CS subset. Plasma TIMP levels declined in both groups.The findings from this study were the identification of increased activation of a cluster of soluble cytokine receptors, which augment not only inflammatory cell maturation but also transmigration in patients with sarcoidosis and patients with cardiac involvement.
Asunto(s)
Citocinas/metabolismo , Cardiopatías/diagnóstico , Tomografía de Emisión de Positrones/métodos , Sarcoidosis/diagnóstico , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Estudios de Evaluación como Asunto , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Cardiopatías/sangre , Cardiopatías/complicaciones , Cardiopatías/patología , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Inflamación/metabolismo , Masculino , Inhibidores de la Metaloproteinasa de la Matriz/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Persona de Mediana Edad , Estudios Prospectivos , Radiofármacos/administración & dosificación , Receptores de Interleucina-2/metabolismo , Receptores del Factor de Necrosis Tumoral/sangre , Medición de Riesgo , Sarcoidosis/sangre , Sarcoidosis/complicaciones , Sarcoidosis/patología , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Elevated Serum Amyloid A (SAA) levels have been found in several inflammatory diseases, including sarcoidosis. SAA is suggested to be involved in sarcoidosis pathogenesis by involvement in granuloma formation and maintenance. We hypothesized that SAA serum levels would be higher in sarcoidosis compared to other non-infectious granulomatous and non-granulomatous diseases. SAA levels were measured in serum from sarcoidosis, Hypersensitivity pneumonitis (HP), and (eosinophilic) granulomatosis with polyangiitis ((E)GPA) patients. Idiopathic pulmonary fibrosis (IPF) patients were included as non-granulomatous disease group. SAA levels of patients with sarcoidosis (31.0 µg/mL), HP (23.4 µg/mL), (E)GPA (36.9 µg/mL), and IPF (22.1 µg/mL) were all higher than SAA levels of healthy controls (10.1 µg/mL). SAA levels did not differ between the diagnostic groups. When SAA serum levels were analyzed in sarcoidosis subgroups, fibrotic sarcoidosis patients showed higher SAA levels than sarcoidosis patients without fibrosis (47.8 µg/mL vs. 29.4 µg/mL, p = 0.005). To conclude, the observation that fibrotic sarcoidosis patients have higher SAA levels, together with our finding that SAA levels were also increased in IPF patients, suggests that SAA may next to granulomatous processes also reflect the process of fibrogenesis. Further studies should clarify the exact role of SAA in fibrosis and the underlying mechanisms involved.
Asunto(s)
Alveolitis Alérgica Extrínseca/sangre , Granulomatosis con Poliangitis/sangre , Fibrosis Pulmonar Idiopática/sangre , Inmunosupresores/uso terapéutico , Sarcoidosis/sangre , Proteína Amiloide A Sérica/metabolismo , Adulto , Anciano , Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/tratamiento farmacológico , Alveolitis Alérgica Extrínseca/patología , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Expresión Génica , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/patología , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/patología , Infliximab/uso terapéutico , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Prednisona/uso terapéutico , Sarcoidosis/diagnóstico , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/patologíaRESUMEN
This study aimed to determine the use of lipid profiling to assess the effects of moderate intensity exercise training (ET) on patients with sarcoidosis. Fourteen patients with sarcoidosis (mean age, 46.0 ± 9.6 years) were examined before and after 3-week of ET programme in hospital settings. Symptoms (fatigue: FAS, dyspnoea: MRC), lung function tests and physical function tests (6 MWT, muscle force) were measured before and after ET. Proton nuclear magnetic resonance (NMR) spectroscopy combined with orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to determine lipid profile before and after ET. Twenty-five NMR signals from lipid compounds were selected for further analysis as well as serum lipid and inflammatory markers. Three weeks of ET results in improvement of symptoms (FAS: 27.5 vs. 21.0; p < 0.001, MRC: 0.86 vs. 0.14; p = 0.002) and physical function (6MWT: 508.43 vs. 547.29; p = 0.039). OPLS-DA analysis of the lipid profiles of patients with sarcoidosis revealed differences among the samples before and after ET, including decreases in fatty acids (p < 0.017), triglycerides (p < 0.022) and total cholesterol (p < 0.020). Other changes included shifts in fatty acids oxidation products and triacylglycerol esters. A short-time, in-hospital exercise training benefits patients with sarcoidosis by enhancing their physical function. Additionally, positive effect on lipid profile was observed also in this study. It is suggested that lipid profiling could become a new prognostic method to assess effects of pulmonary rehabilitation in patients with sarcoidosis.
Asunto(s)
Ejercicio Físico , Lípidos/sangre , Sarcoidosis/sangre , Sarcoidosis/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Sarcoidosis/fisiopatologíaRESUMEN
Background Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) share many histopathologic and clinical features. Whether they are parts of a one-disease continuum has been discussed. Methods and Results We compared medical record data of 351 CS and 28 GCM cases diagnosed in Finland since the late 1980s and followed until February 2018 for a composite end point of cardiac death, aborted sudden death, and heart transplantation. Heart failure was the presenting manifestation in 50% versus 15% (P<0.001), and high-grade atrioventricular block in 21% versus 43% (P=0.044), of GCM and CS, respectively. At presentation, left ventricular ejection fraction was ≤50% in 81% of cases of GCM versus in 48% of CS (P=0.004). The median (interquartile range) of plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) was 5273 (2782-11309) ng/L on admission in GCM versus 859 (290-1950) ng/L in CS (P<0.001), and cardiac troponin T exceeded 50 ng/L in 17 of 19 cases of GCM versus in 48 of 239 cases of CS (P<0.001). The 5-year estimate of event-free survival was 77% (95% CI, 72%-82%) in CS versus 27% (95% CI, 10%-45%) in GCM (P<0.001). By Cox regression analysis, GCM predicted cardiac events with a hazard ratio of 5.16 (95% CI, 2.82-9.45), which, however, decreased to 1.58 (95% CI, 0.71-3.52) after inclusion of markers of myocardial injury and dysfunction in the model. Conclusions GCM differs from CS in presenting with more extensive myocardial injury and having worse long-term outcome. Yet the key determinant of prognosis appears to be the extent of myocardial injury rather than the histopathologic diagnosis.
Asunto(s)
Cardiomiopatías/diagnóstico , Predicción , Células Gigantes/patología , Miocardio/patología , Péptido Natriurético Encefálico/sangre , Vigilancia de la Población , Sarcoidosis/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Cardiomiopatías/sangre , Cardiomiopatías/epidemiología , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoidosis/sangre , Sarcoidosis/epidemiología , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Cardiac sarcoidosis is difficult to diagnose, often requiring expensive and inconvenient advanced imaging techniques. Circulating exosomes contain genetic material, such as microRNA (miRNA), that are derived from diseased tissues and may serve as potential disease-specific biomarkers. We thus sought to determine whether circulating exosome-derived miRNA expression patterns would distinguish cardiac sarcoidosis (CS) from acute myocardial infarction (AMI). METHODS: Plasma and serum samples conforming to CS, AMI or disease-free controls were procured from the Biologic Specimen and Data Repository Information Coordinating Center repository and National Jewish Health. Next generation sequencing (NGS) was performed on exosome-derived total RNA (n = 10 for each group), and miRNA expression levels were compared after normalization using housekeeping miRNA. Quality assurance measures excluded poor quality RNA samples. Differentially expressed (DE) miRNA patterns, based upon >2-fold change (p < 0.01), were established in CS compared to controls, and in CS compared to AMI. Relative expression of several DE-miRNA were validated by qRT-PCR. RESULTS: Despite the advanced age of the stored samples (~5-30 years), the quality of the exosome-derived miRNA was intact in ~88% of samples. Comparing plasma exosomal miRNA in CS versus controls, NGS yielded 18 DE transcripts (12 up-regulated, 6 down-regulated), including miRNA previously implicated in mechanisms of myocardial injury (miR-92, miR-21) and immune responses (miR-618, miR-27a). NGS further yielded 52 DE miRNA in serum exosomes from CS versus AMI: 5 up-regulated in CS; 47 up-regulated in AMI, including transcripts previously detected in AMI patients (miR-1-1, miR-133a, miR-208b, miR-423, miR-499). Five miRNAs with increased DE in CS included two isoforms of miR-624 and miR-144, previously reported as markers of cardiomyopathy. CONCLUSIONS: MiRNA patterns of exosomes derived from CS and AMI patients are distinct, suggesting that circulating exosomal miRNA patterns could serve as disease biomarkers. Further studies are required to establish their specificity relative to other cardiac disorders.
Asunto(s)
MicroARN Circulante/sangre , Exosomas/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Infarto del Miocardio/sangre , Sarcoidosis/sangre , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Sarcoidosis/diagnósticoRESUMEN
A 27-year-old woman presented to the dermatology department with a 1-year history of multiple asymptomatic violaceous lesions on her upper and lower extremities, trunk and abdomen. The lesions were firm on palpation. She had no other associated symptoms and the rest of the examination was unremarkable. An incisional biopsy showed multiple confluent granulomas composed of histiocytes devoid of necrosis surrounded by a rim of lymphocytes extending to the subcutaneous fat consistent with the diagnosis of subcutaneous sarcoidosis. The serum ACE assay was elevated at 134 IU/L. Other blood tests including complete blood count, renal and liver function tests, serum calcium and phosphate were within normal ranges and chest X-ray was unremarkable. Complete remission was achieved with an intralesional triamcinolone injection (10 mg/mL) for a few sessions. Subcutaneous sarcoidosis is a rare variation and its diagnosis requires a high index of suspicion.
Asunto(s)
Sarcoidosis/diagnóstico , Enfermedades de la Piel/diagnóstico , Triamcinolona/administración & dosificación , Adulto , Enfermedades Asintomáticas/terapia , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Inyecciones Intralesiones , Peptidil-Dipeptidasa A/análisis , Sarcoidosis/sangre , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/patología , Piel/patología , Enfermedades de la Piel/sangre , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: Increased thickness of epicardial adipose tissue (EAT) and the total coronary artery calcium score (TCACS) are independent predictors of atherosclerosis. The aim of this study was to investigate whether EAT thickness, measured using thoracic computed tomography, and TCACS were greater in patients with sarcoidosis. METHODS: This was a retrospective study. The details of participants who presented at the cardiology and pulmonology outpatient clinics between January 2011 and December 2018 with dyspnea, chest pain, or palpitations from the hospital data system were reviewed. Patients with transthoracic echocardiography and thorax computed tomography (CT) (CT) records were identified, and those who were diagnosed with sarcoidosis, had no other health problems, and did not take any medication were included in the study. RESULTS: A total of 45 controls and 78 sarcoidosis patients were enrolled. The mean age of the controls was 46.15±13.1 years, while it was 46.26±12.37 years in the sarcoidosis group, which represented no significant difference between the groups (p>0.05). When the groups were compared in terms of a fasting blood test, erythrocyte sedimentation rate (ESR), TCACS, EAT thickness, levels of C-reactive protein (CRP), total cholesterol, low-density lipoprotein (LDL), and triglycerides, it was observed that CRP and EAT thickness were higher in the sarcoidosis group. CONCLUSION: The results of this study indicated that the thickness of EAT calculated using thorax CT was greater in sarcoidosis patients; however, the TCACS was similar in both groups. In addition, there was a positive correlation between EAT thickness and the level of total cholesterol, LDL, triglycerides, CRP, and the sedimentation rate. These findings suggest that atherosclerosis may start earlier in those with sarcoidosis than in the healthy population.
Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Pericardio/diagnóstico por imagen , Sarcoidosis/diagnóstico por imagen , Calcificación Vascular/diagnóstico por imagen , Aterosclerosis/sangre , Aterosclerosis/diagnóstico por imagen , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoidosis/sangre , Tomografía Computarizada por Rayos XRESUMEN
Organic and inorganic antigens were studied simultaneously in the same cohort of sarcoidosis patients to investigate whether correlations between clinical characteristics and immunological sensitization could reveal new phenotypes. Sensitization to antigens of mycobacteria, Propionibacterium acnes catalase and vimentin was investigated in 201 sarcoidosis and 51 obstructive sleep apnoea patients, serving as control group. Sensitization to aluminium, beryllium, silica and zirconium was also studied in 105 of the sarcoidosis patients and in 24 of the controls. A significantly higher percentage of sarcoidosis patients (27·6%) than controls (4·2%) had an immunological response to metals or silica (P = 0·014). A higher percentage of these sarcoidosis patients showed fibrosis on chest X-ray 5 years after the diagnosis (69·2 versus 30·3%, P = 0·016). No significant differences in mycobacterial or vimentin enzyme-linked immunospot (ELISPOT) assay results were observed between sarcoidosis and control patients. A significantly lower percentage of sarcoidosis patients (3·5%) than control patients (15·7%) had a positive ELISPOT for P. acnes catalase (P = 0·003). However, sarcoidosis patients sensitized to P. acnes catalase were more likely to have skin involvement, while sarcoidosis patients sensitized to mycobacterial antigens were more likely to have cardiac involvement. Our study suggests a more prominent role for inorganic triggers in sarcoidosis pathogenesis than previously thought. Immunological sensitization to inorganic antigens was associated with development of fibrotic sarcoidosis. No association was found between sensitization to bacterial antigens or vimentin and sarcoidosis in Dutch patients. However, our data suggest that trigger-related phenotypes can exist in the heterogeneous population of sarcoidosis patients.
Asunto(s)
Aluminio/inmunología , Antígenos/inmunología , Berilio/inmunología , Sarcoidosis/inmunología , Dióxido de Silicio/inmunología , Circonio/inmunología , Adulto , Aluminio/sangre , Antígenos/sangre , Proteínas Bacterianas/sangre , Proteínas Bacterianas/inmunología , Berilio/sangre , Catalasa/sangre , Catalasa/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propionibacterium acnes/inmunología , Propionibacterium acnes/metabolismo , Sarcoidosis/sangre , Dióxido de Silicio/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/inmunología , Vimentina/sangre , Vimentina/inmunología , Circonio/sangreRESUMEN
An elevated blood angiotensin I-converting enzyme (ACE) supports diagnosis of sarcoidosis and Gaucher disease. However, some ACE mutations increase ACE shedding, and patients with these mutations are therefore at risk of being incorrectly diagnosed with sarcoidosis because of elevated serum ACE levels. We applied a novel approach called "ACE phenotyping" to identify possible ACE mutations in 3 pulmonary clinic patients that had suspected sarcoidosis based on elevated blood ACE levels. Conformational fingerprinting of ACE indicated that these mutations may be localized in the stalk region of the protein and these were confirmed by whole exome sequencing. Index patient 1 (IP1) had a mutation (P1199L) that had been previously identified, while the other 2 patients had novel ACE mutations. IP2 had 2 mutations, T887M and N1196K (eliminating a putative glycosylation site), while IP3 had a stop codon mutation Q1124X (eliminating the transmembrane anchor). We also performed a comprehensive analysis of the existing database of all ACE mutations to estimate the proportion of mutations increasing ACE shedding. The frequency of ACE mutations resulting in increased blood ACE levels may be much higher than previously estimated. ACE phenotyping, together with whole exome sequencing, is a diagnostic approach that could prevent unnecessary invasive and/or costly diagnostic procedures, or potentially harmful treatment for patients misdiagnosed on the basis of elevated blood ACE levels.
Asunto(s)
Peptidil-Dipeptidasa A/sangre , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Sarcoidosis/sangre , Sarcoidosis/diagnóstico , Anciano , Biomarcadores/sangre , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Simulación del Acoplamiento Molecular , Mapeo Peptídico , Unión Proteica , Conformación ProteicaRESUMEN
Sarcoidosis is a multisystemic chronic inflammatory disease that the specific etiology is not known clearly. The aim of this study is, to investigate the presence of subclinical atherosclerosis and endothelial dysfunction by using carotid intima-media thickness and flow-mediated dilatation measurements, measuring the copeptin values, which is a stress marker, and interpreting the association of copeptin values with these two variables in sarcoidosis patients without conventional risk factors for coronary artery disease. Seventy-four patients (50 f, 24 m) with histopathological diagnosis of sarcoidosis and 60 healthy volunteers (35 f, 25 m) with similar sociodemographic characteristics were included in this study. CIMT, FMD, and serum copeptin levels of all participants were measured. The values of CIMT and Copeptin in sarcoidosis patients were significantly higher (p = 0.001, p < 0.001 respectively), and FMD was significantly lower (p = 0.01) than the control group. In sarcoidosis patients not significant correlation found among CIMT with copeptin (r: 0.16, p = 0.18) and FMD with copeptin (r: 0.01, p = 0.96). With the demonstration of the presence of subclinical atherosclerosis and endothelial dysfunction, we suggest; sarcoidosis patients may be followed more closely in terms of cardiovascular diseases. And new studies are needed to investigate the pathophysiology and the effects of high copeptin levels in sarcoidosis patients.