Marker Of Sarcoidosis Research Articles

Isolated ocular sarcoidosis

A rare clinical case of a patient with isolated sarcoidosis of the eyes is presented. Sarcoidosis is a polyethological disease, the morphological feature of which is the formation of epithelioid cell granulomas in various organs and tissues, which is accompanied by a violation of their structure and function. Both congenital and adaptive immune systems are involved in the pathogenesis of sarcoidosis, with damage to lymph nodes, lungs, skin, organ of vision, etc. Risk factors for the development of sarcoidosis have not been definitively established. Environmental factors and genetic predisposition play a crucial role in the development of the disease. The above clinical observation demonstrates the polymorphism of the clinical picture of isolated ocular sarcoidosis. In addition to standard ophthalmic examination methods, the genetic method of reverse transcription and quantitative polymerase chain reaction (RT-PCR, English qRT-PCR) was also used to determine the expression profile of signature microRNAs as potential diagnostic markers of sarcoidosis of the organ of vision.An increase in the expression level of hsa-miR-455-3p, hsa-miR-4663, hsamiR68063p, hsa-miR-450b-5p, hsa-miR-6716-3p, hsa-miR-5000-5p, hsa-miR150-5p can be considered as potential diagnostic biomarkers of sarcoid lesion of eye structures. With sarcoidosis, the involvement of the lacrimal gland is possible. In the presented clinical observation, this was indicated by the results of a functional examination, sonographic signs: revealed multiple linear tubular hyperechoic structures and a decrease in blood flow velocity in the ocular and lacrimal arteries, as well as an increase in the expression activity of hsa-miR150-5p (p < 0.05). In order to prevent possible damage to the ocular surface due to the development of lacrimal gland dysfunction, it is advisable to prescribe local tear replacement therapy with hyaluronic acid preparations. Such effective drugs include tear substitutes of the Optinol® line: “Optinol® Express Moisture” and “Optinol® Deep Moisture”.

Determination of immunological biomarkers in sarcoidosis and their relation to disease activity

Sarcoidosis is a multisystem granulomatous disease of unknown origin. Ninety percent of patients with sarcoidosis have lung involvement. The onset can be acute or non-acute and the severity of sarcoidosis ranges widely from asymptomatic patients with accidental radiographic findings to patients with severe organ involvement. This case control analytic prospective study was conducted at the Chest Clinic, Al Zahraa hospital, to assess the diagnostic value of serum soluble interleukin 2 receptor (sIL-2R), cluster of differentiation 4 (CD4)/CD8 ratio and CD103 in sarcoidosis. We investigated the value of serum sIL-2R using ELISA and blood CD103, blood CD4/CD8 ratio using flow cytometry for 30 cases of sarcoidosis in different stages and 30 control persons to detect their use as a marker for diagnosis. We found a significant increase in sIL-2R in the sarcoidosis group as compared to the control group (p˂0.0001), while there was a significant decrease in CD103/CD4 in sarcoidosis group as compared to the control group (p <0.001). In conclusion, sIL-2R and CD103 can be used as diagnostic markers for sarcoidosis.

Pan-immune-inflammation value and systemic immune-inflammation index: Are they useful markers in sarcoidosis?

Background/Aim: Sarcoidosis is a multisystem inflammatory disease characterized by the infiltration of various organs. Due to the lack of a widely-accepted biomarker, researchers have explored alternative and previously unexplored parameters in sarcoidosis. This study aimed to investigate the utility of various markers, including the systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV), in patients with sarcoidosis. Methods: A case-control study was conducted between January 2019 and February 2023. The study included 75 patients diagnosed with sarcoidosis, and 93 healthy individuals matched for age, sex, and body mass index. Sarcoidosis-related features, such as lung stage and extrapulmonary involvement, were recorded. The researchers investigated SII, PIV, procalcitonin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), other biochemical results, and complete blood counts (including neutrophil, lymphocyte, monocyte, platelet counts, hemoglobin, mean platelet volume [MPV], and red cell distribution width [RDW]). Results: The age and sex distribution were similar in both the case and control groups (P=0.258 and P=0.196, respectively). The patient group had a significantly lower absolute lymphocyte count than the control group (P=0.035). Patients’ RDW (P=0.007), platelet-to-lymphocyte ratio (P=0.028), and ESR (P<0.001) values were significantly higher compared to controls. No significant difference was observed between the two groups regarding other variables, including PIV and SII. There was a significant weak positive correlation between PIV and lung stage, as well as between MPV and the presence of erythema nodosum. Conclusion: PIV and SII values in patients with sarcoidosis were similar to controls. The positive correlations between PIV and lung stage and between MPV and erythema nodosum suggest potential relationships with sarcoidosis-related features and demonstrate the value of these readily available and inexpensive markers in patient management. Comprehensive studies are needed to clarify whether SII and/or PIV can be used to assess the characteristics of patients with sarcoidosis.

A rare case of unilateral acute posterior multifocal placoid pigment epitheliopathy with features of Vogt-Koyanagi-Harada disease

The purpose of this study is to report a rare case of unilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with features of Vogt-Koyanagi-Harada (VKH) disease. Both the diseases have their own unique presentations and can lead to vision loss in the affected eye. Overlapping features of both diseases in the same eye is rare. A 28-year-old healthy female presented with loss of vision in her right eye for 10 days duration. Visual acuity in the affected eye was 20/200, N36. Fundus examination revealed numerous creamy yellow lesions overlying the posterior pole with subretinal fluid. Further investigations including fundus fluorescein angiography and optical coherence tomography were suggestive of overlapping features of both APMPPE and VKH disease. Baseline laboratory investigations and markers for Sarcoidosis, Tuberculosis, and Syphilis were normal. The patient was treated with tapering doses of oral steroids. One month following initiation of treatment, the vision had improved to 20/20, N6 with complete resolution of subretinal fluid in the right eye. The overlapping clinical and imaging features suggest that both diseases may be a part of a common inflammatory process that secondarily damages the outer retinal structures.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells in Pulmonary Sarcoidosis.

BackgroundSarcoidosis is a granulomatous systemic disease of unknown etiology. Mononuclear cells such as macrophages or lymphocytes in lung tissue and hilar or mediastinal lymph nodes have been recognized to play an essential role in granuloma formation in pulmonary sarcoidosis. Peripheral blood mononuclear cells (PBMCs) consist of several immunocompetent cells and have been shown to play a mechanistic role in the pathogenesis of sarcoidosis. However, the genetic modifications that occur in bulk PBMCs of sarcoidosis remain to be elucidated.PurposeThis study aimed to explore the pathobiological markers of sarcoidosis in PBMCs by comparing the transcriptional signature of PBMCs from patients with pulmonary sarcoidosis with those of healthy controls by RNA sequencing.MethodsPBMC samples were collected from subjects with pulmonary sarcoidosis with no steroid/immunosuppressant drugs (n = 8) and healthy controls (n = 11) from August 2020 to April 2021, and RNA sequencing was performed with the PBMC samples.ResultsPrincipal component analysis using RNA sequencing datasets comparing pulmonary sarcoidosis with healthy controls revealed that the two groups appeared to be differentiated, in which 270 differentially expressed genes were found in PBMCs between sarcoidosis and healthy controls. Enrichment analysis for gene ontology suggested that some biological processes related to the pathobiology of sarcoidosis, such as cellular response to interleukin (IL)-1 and IFN-γ, regulation of IL-6 production, IL-8 secretion, regulation of mononuclear cell migration, and response to lipopolysaccharide, were involved. Enrichment analysis of the KEGG pathway indicated the involvement of tumor necrosis factor (TNF), toll-like receptor signaling, IL-17 signaling pathways, phagosomes, and ribosomes. Most of the genes involved in TNF and IL-17 signaling pathways and phagosomes were upregulated, while most of the ribosome-related genes were downregulated.ConclusionThe present study demonstrated that bulk gene expression patterns in PBMCs were different between patients with pulmonary sarcoidosis and healthy controls. The changes in the gene expression pattern of PBMCs could reflect the existence of sarcoidosis lesions and influence granuloma formation in sarcoidosis. These new findings are important to strengthen our understanding of the etiology and pathobiology of sarcoidosis and indicate a potential therapeutic target for sarcoidosis.

BATF2 and PDK4 as diagnostic molecular markers of sarcoidosis and their relationship with immune infiltration.

BackgroundSarcoidosis (SA) is an immune disorder disease featuring granulomas formation with a controversial etiopathogenesis. We aimed to uncover potential markers for SA diagnosis and explore how immune cell infiltration contributes to the pathogenesis of SA.MethodsSarcoidosis GSE83456 samples and GSE42834 from Gene Expression Omnibus (GEO) were analyzed as the training and external validation sets, respectively. Firstly, R statistical software was employed to uncover the differentially expressed genes (DEGs) of GSE83456. Weighted gene co-expression network analysis (WGCNA) was used to reveal the key module of DEGs. Secondly, the genes of the key module were used to analyze functional correlations. Thirdly, support vector machine (SVM) algorithms and least absolute shrinkage and selection operator (LASSO) logistic regression were applied for screening and verification of the diagnostic markers for key module genes. Finally, the infiltration of immune cells in SA patients’ blood samples was assessed by Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), after which correlations of diagnostic markers immune cell and infiltration were explored. Serum samples collected from human research participants were used for confirmatory analysis of bioinformatics. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of BATF2 and PDK4.ResultsIn total, 580 DEGs were identified from the key module. The genes PDK4 [area under the curve (AUC) =0.942] and BATF4 (AUC =0.980) were revealed as diagnostic markers of SAs. The diagnostic power of the 2 genes was verified in GSE42834. We found that monocytes, T cells regulatory (Tregs), mast cells, macrophages, natural killer (NK) cells, and dendritic cells (DC) may contribute to SA development through immune cell infiltration study. In addition, PDK4 and BATF4 were closely associated with these immune cells. Both BATF2 and PDK4 were highly expressed in active pulmonary SA. Using non-SA patients as controls, the AUC of serum PDK4, BATF2, and their combination for the diagnosis of active pulmonary SA was 0.798 (95% CI: 0.701 to 0.876), 0.895 (95% CI: 0.813 to 0.950), and 0.910 (95% CI: 0.831 to 0.960), respectively.ConclusionsThe genes PDK4 and BATF4 could be used as diagnostic markers of active pulmonary SA. Immune cell infiltration severs an important role in SA.

P16‐10: Usefulness of plasma and urine lysophospholipids‐producing enzymes as a prognostic marker for sarcoidosis

P16‐10: Usefulness of plasma and urine lysophospholipids‐producing enzymes as a prognostic marker for sarcoidosis

Speckle tracking echocardiography as a promising tool for the prognostic assessment of patients with sarcoidosis

Abstract Background Sarcoidosis is a chronic granulomatous disease characterized by multiorgan inflammatory involvement and recurrent relapses with significant impact on morbidity and mortality. The prognostic assessment of these patients is still challenging. Although the international guidelines didn't recommend basic transthoracic echocardiography (TTE) for diagnostic and prognostic assessment of sarcoidosis, speckle tracking echocardiography (STE) has emerged as more sensitive for the early detection of cardiac sarcoidosis and outcome. Purpose This prospective study aimed to assess the potential value of STE parameters for the prediction of major adverse cardiac events (MACE) and sarcoidosis relapse. Methods Consecutive patients with confirmed diagnosis of sarcoidosis who underwent transthoracic echocardiography (TTE) and subsequent pulmonary function tests (PFTs) were enrolled. Patients with acute events or treatment escalation between TTE and PFTs and previous cardiac surgery were excluded. All patients were followed for sarcoidosis relapse requiring increase in step-up therapy and MACE (cardiovascular death, cardiovascular hospitalizations, arrhythmias). Results 172 patients were included (111 females, 57.4±12.6 years); 56 patients showed extrapulmonary localizations of sarcoidosis; at baseline, 99 patients were on steroid and/or immunosuppressive therapy. During a median follow up of 2217 days, 8 deaths (3 cardiovascular deaths), 23 MACE and 36 sarcoidosis relapses were reported. Patients with MACE were older (p=0.0022), but didn't show significant differences in PFTs and sarcoidosis phenotype. LV global longitudinal strain (GLS) was the only echocardiographic index to show significant differences (lower values) in patients with MACE (p=0.025). LV GLS ≤17.13% (absolute value) was identified as a fair predictor of MACE both with ROC curves (AUC=0.64) and Kaplan Meier analysis (Fig. 1). No significant differences of demographic, clinical, functional, and therapeutic data were observed between patients with/without sarcoidosis relapse. TTE revealed a significant reduction of LV ejection fraction (p=0.0432), tricuspid annular plane systolic excursion (TAPSE, p=0.0272) and global peak atrial longitudinal strain (PALS, p=0.0012) in patients with relapse. Among these 3 parameters, PALS ≤28.5% showed to be the best predictor of sarcoidosis relapse with ROC (AUC=0.7155) and Kaplan Meier curves (Fig. 2). Conclusions Our results highlight a potential role of LV GLS and PALS as prognostic markers in sarcoidosis, suggesting the use of STE in the clinical management of these patients, regardless the evidence or the suspect of cardiac localizations of the disease. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Strain Echocardiography Is a Promising Tool for the Prognostic Assessment of Sarcoidosis.

Sarcoidosis is a systemic chronic granulomatous disease with significant morbidity and mortality. Although basic transthoracic echocardiography (TTE) is not recommended for the assessment of sarcoidosis, speckle tracking echocardiography (STE) has emerged as more sensitive for the early detection of cardiac sarcoidosis and its outcome. The aim of the study was to assess the utility of left atrial and left ventricular longitudinal STE for the prediction of major adverse cardiac events (MACE) and sarcoidosis relapses. We enrolled 172 consecutive patients with sarcoidosis who underwent TTE and pulmonary function tests (PFTs). All patients were followed for a sarcoidosis relapse and MACE. During a median follow-up of 2217 days, 8 deaths, 23 MACE and 36 sarcoidosis relapses were observed. LV global longitudinal strain (GLS) was significantly lower in patients with MACE (p = 0.025). LV-GLS < 17.13% (absolute value) was identified as a fair predictor of MACE. Concerning the sarcoidosis control, TTE revealed a reduction of the LV ejection fraction (p = 0.0432), tricuspid annular plane systolic excursion (p = 0.0272) and global peak atrial longitudinal strain (PALS, p = 0.0012) in patients with relapses. PALS < 28.5% was the best predictor of a sarcoidosis relapse. Our results highlight a potential role of LV-GLS and PALS as prognostic markers in sarcoidosis, supporting the use of STE in the clinical management of these patients.

Unsupervised Clustering Reveals Sarcoidosis Phenotypes Marked by a Reduction in Lymphocytes Relate to Increased Inflammatory Activity on 18FDG-PET/CT.

Introduction: Sarcoidosis is a T-helper cell mediated disease characterized by granulomatous inflammation. We posited that unsupervised clustering of various features in sarcoidosis would establish phenotypes associated with inflammatory activity measured by 18FDG-PET/CT. Our goal was to identify unique features capable of distinguishing clusters and subsequently examine the relationship with FDG avidity to substantiate their potential use as markers for sarcoidosis inflammation.Methods: We performed a retrospective study of a diverse, but primarily African American, cohort of 58 subjects with biopsy proven sarcoidosis followed at the University of Illinois Bernie Mac Sarcoidosis Center and Center for Lung Health who underwent 18FDG-PET/CT scan. Demographic, therapeutic, radiographic, and laboratory data were utilized in unsupervised cluster analysis to identify sarcoidosis phenotypes. The association between clusters, their defining features, and quantitative measurements on 18FDG-PET/CT was determined. The relevance of these features as markers of 18FDG-PET/CT inflammatory activity was also investigated.Results: Clustering determined three distinct phenotypes: (1) a predominantly African American cluster with chronic, quiescent disease, (2) a predominantly African American cluster with elevated conventional inflammatory markers, advanced pulmonary disease and extrathoracic involvement, and (3) a predominantly Caucasian cluster characterized by reduced lymphocyte counts and acute disease. In contrast to the chronic quiescent cluster, Clusters 2 and 3 were defined by significantly greater FDG avidity on 18FDG-PET/CT. Despite similarly increased inflammatory activity on 18FDG-PET/CT, Clusters 2, and 3 differed with regards to extrathoracic FDG avidity and circulating lymphocyte profiles, specifically CD4+ T-cells. Notably, absolute lymphocyte counts and CD4+ T-cell counts were found to predict 18FDG-PET/CT inflammatory activity by receiver operating curve analysis with a 69.2 and 73.42% area under the curve, respectively.Conclusions: Utilizing cluster analysis, three distinct phenotypes of sarcoidosis were identified with significant variation in race, disease chronicity, and serologic markers of inflammation. These phenotypes displayed varying levels of circulating inflammatory cells. Additionally, reduction in lymphocytes, specifically CD4+ T-cells, was significantly related to activity on 18FDG-PET/CT. Though future studies are warranted, these findings suggest that peripheral lymphocyte counts may be considered a determinant of sarcoidosis phenotypes and an indicator of active inflammation on 18FDG-PET/CT.

Soluble interleukin-2 receptor in exhaled breath condensate in pulmonary sarcoidosis: a cross-sectional pilot study

Introduction. Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is an urgent need to identify new and novel biomarkers to help differentiate between clinical phenotypes and guide clinical decisions with respect to commencing and monitoring treatment. Across the spectrum of respiratory disease there has been a growing interest in the role of breath-based biomarkers given their non-invasive nature and ability to repeat sampling with ease for serial monitoring. Soluble interleukin-2 receptor (sIL2R) in bronchoalveolar lavage and serum correlates with disease activity in sarcoidosis; however, no previous study has evaluated sIL2R in exhaled breath. Objectives. The main aim of this cross-sectional case-controlled pilot study was to determine the concentration of sIL2R in exhaled breath condensate (EBC) from patients with recently diagnosed sarcoidosis compared to healthy volunteers and to establish, if present, if this correlated with markers of disease activity, pulmonary function tests and serological markers used in current clinical practice. Methods. Paired serum and EBC samples were collected from twelve treatment naïve patients with histologically proven sarcoidosis diagnosed during the previous six months and compared to twelve healthy volunteers matched for age and gender. Results. Mean concentration of serum sIL2R was significantly elevated in participants with sarcoidosis compared to healthy controls (1584.3 ± 489.1 versus 874.2 ± 235.7 pg mL−1; p = 0.001). Soluble interleukin-2 receptor in EBC was detectable in only five subjects including three participants with sarcoidosis. The range of sIL2R across all five samples was 148.0–288.2 pg mL−1 with the two highest concentrations observed in two participants with sarcoidosis. There was no significant difference observed in EBC sIL2R between sarcoidosis and healthy controls (p = 0.71). No apparent correlations were observed between EBC sIL2R and radiological stage, pulmonary function tests or serological markers. Conclusion. Soluble interleukin-2 receptor is detectable in EBC; however, the findings from our study do not support its role as a diagnostic marker in sarcoidosis. Further research is required to evaluate its prognostic utility.

Relevance of concurrent hypercalcemia in ureteric sarcoidosis complicated with bladder urothelial carcinoma: a case report

BackgroundSarcoidosis is a multisystem inflammatory disorder and can affect any organ; however, ureteric involvement is extremely rare with only four cases reported in the literature to date, all of which were diagnosed with surgical ureteral resection including a nephroureterectomy. This study reports the first case of ureteric sarcoidosis controlled with medical therapy where a differential diagnosis was performed based on the diagnostic clue of hypercalcemia. A definitive diagnosis was established without surgical resection of the ureter.Case presentationA 60-year-old man presented with anorexia and weight loss. Blood tests showed renal dysfunction and hypercalcemia. Computed tomography revealed left hydronephrosis associated with left lower ureteral wall thickening, which showed high signal intensity on diffusion-weighted magnetic resonance imaging. Similarly, we detected a bladder tumor on cystoscopy, and a 2-cm-long stenosis was revealed by retrograde ureterography; therefore, ureteral cancer was suspected. Meanwhile, considering the clinical implication of hypercalcemia, a differential diagnosis of sarcoidosis was established based on elevated levels of sarcoidosis markers. Fluorodeoxyglucose positron emission tomography showed fluorodeoxyglucose accumulation in the left lower ureter, skin, and muscles, suggestive of ureteric sarcoidosis with systemic sarcoid nodules. For a definitive diagnosis, transurethral resection of the bladder tumor and ureteroscopic biopsy were performed. Histopathological examination revealed ureteric sarcoidosis with bladder urothelial carcinoma. Following an oral administration of prednisolone, hypercalcemia instantly resolved, the renal function immediately improved, and the left ureteral lesion showed complete resolution with no recurrence.ConclusionsIn this case, the co-occurrence of ureteral lesion with bladder tumor evoked a diagnosis of ureteral cancer. However, considering a case of ureteral lesion complicated with hypercalcemia, assessment for differential diagnosis was performed based on the calcium metabolism and sarcoidosis markers. In cases of suspected ureteric sarcoidosis from the assessment, pathological evaluation with ureteroscopic biopsy should be performed to avoid nephroureterectomy.

Value of serum soluble interleukin-2 receptor as a diagnostic and predictive biomarker in sarcoidosis

ABSTRACT Background Differentiating between interstitial lung diseases (ILD) is challenging. Serum soluble interleukin 2 receptor (sIL-2R) is used as a diagnostic marker in sarcoidosis, but its diagnostic value has not yet been studied in other ILDs like Idiopathic Pulmonary Fibrosis (IPF) or Hypersensitivity Pneumonitis (HP). Also, the prognostic value of sIL-2R in sarcoidosis remains unknown. Methods This retrospective cohort study included 121 patients with sarcoidosis, 35 with cHP, 62 with IPF (idiopathic pulmonary fibrosis) and 70 healthy controls. Serum sIL-2R levels were determined at diagnosis. Follow-up data were available for patients with chronic sarcoidosis (n = 64) and patients with non-chronic sarcoidosis (n = 29). Results Patients with sarcoidosis had higher sIL-2R levels (median 5418 pg/mL) than patients with cHP (median 4015 pg/mL, P = 0.002) and IPF (median 4192 pg/mL, P = 0.034). No differences were found between patients with cHP and IPF. Logistic regression revealed that sIL-2R at diagnosis is a significant predictor of the development of chronic sarcoidosis (OR = 2.1, P = 0.032). Conclusion High levels of sIL-2R are suggestive of sarcoidosis, although a broad overlap exists in sIL-2R levels across sarcoidosis, cHP, and IPF. High levels of sIL-2R might serve as a prognostic biomarker for chronicity.

Papulo-Nodular Reactions in Black Tattoos as Markers of Sarcoidosis: Study of 92 Tattoo Reactions from a Hospital Material

Background/Aims: Sarcoidosis is, from historical data, suggested to be more prevalent among patients with tattoo reactions. We aimed to evaluate this association in a systematic study. Methods: This is a consecutive study of patients with tattoo complications, diagnosed in the “Tattoo Clinic” at Bispebjerg University Hospital in Copenhagen, Denmark, from 2008 to 2015, based on clinical assessment and histology. From the overall group of 494 tattoo complications in 406 patients, 92 reactions in 72 patients showed a papulo-nodular pattern studied for local and systemic sarcoidosis, since sarcoidosis is expected to be nodular. Results: Of the 92 reactions with a papulo-nodular pattern, 27 (29%) reactions in 19 patients were diagnosed as cutaneous or systemic sarcoidosis, supported by histology; 65 (71%) were diagnosed as non-sarcoidosis due to histology and no clinical sarcoid manifestations. “Rush phenomenon” with concomitant reaction in many other black tattoos, triggered by a recent tattoo with a papulo-nodular reaction, was observed in 70% in the sarcoidosis group and 28% in the non-sarcoidosis group, indicating a predisposing factor which may be autoimmune and linked with sarcoidosis. Agglomerates of black pigment forming foreign bodies may in the predisposed individual trigger widespread reaction in the skin and internal organs. Conclusion: Black tattoos with papulo-nodular reactions should be seen as markers of sarcoidosis. Papulo-nodular reactions may, as triggers, induce widespread reactions in other black tattoos - a “rush phenomenon” - depending on individual predisposition. Sarcoidosis is estimated to be 500-fold increased in papulo-nodular reactions compared to the prevalence in the general population, and the association with black tattoos is strong.

Sarcoidosis: Follow-up With 18f-FDG PET/CT After Different Therapy

SESSION TITLE: Imaging SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: The purpose of this study was to assess the utility of 18F-FDG PET/CT (PET/CT scan) for detection of inflammation in granulomatous sites and management of sarcoidosis patients with different therapy. The specific aims were to compare PET/CT scan findings with x-ray score, serum levels of chitotriosidase (CTO), serum angiotensin converting enzyme (sACE) at the time of diagnosis and at different SUV-Max activity in different organs in body and to evaluate therapies with glucocorticoid and antimicotic. METHODS: The study comprises 86 sarcoidosis patients who underwent PET/CT scan between March 2010 and April 2015, at the time of diagnosis and at the end of therapy and follow-up without therapy. The presence of inflammatory activity was assessed using PET/CT scan. Correlations between PET/CT scan findings (MaxSUV, MaxSUV in lung parenchyma, MaxSUV in lymph nodes), CTO, sACE, radiological evaluation (X-ray score) and pulmonary function at the time of diagnosis and at follow-up were calculated for all patients and separately for patients without therapy and patients receiving antifungal and/or corticosteroid therapy. RESULTS: PET/CT scan findings at the time of diagnosis MaxSUV1 10.8±1.1; MaxParenhim1 2.2±0.4; MaxLymphN1 8.3±1.1. MaxSUV1 were correlated with X-ray score-1 (r=0.369, p=0.001; with sACE (r=0.266, p=0.017) with CTO (r=0.483, p=0.000). MaxSUV2 was 6.2±1.1 in whole group without correlations with markers except X-ray score-2 (p=0.055). Correlations with MaxSUV2 were only present in the group with antifungal therapy (CTO2, r=0.509, p=0.003) and X-ray score-2 (r=0.533, p=0.001). In the group without therapy and follow-up without therapy, MaxSUV2 correlated with X-ray score-2 (r=0.567, p=0.014). No correlations were found between first and second PET/CT scan and pulmonary function tests. CONCLUSIONS: The results show that PET/CT scan is useful as a diagnostic method for detecting active inflammatory granulomatous sites at the time of diagnosis sarcoidosis, especially those with normal level of sACE and normal DLco. It is also useful to determine the spread of active disease through the body and to assist in the decision to adjust the therapy. For the follow-up the effectiveness of therapy or for evaluate the activities of the disease, only after antifungal treatment the PET/CT scan correlated with other biomarkers of the activity of sarcoidosis. PET/CT scan had different information about the activity of disease comparing the other markers of sarcoidosis. The results suggest that follow up PET/CT is not needed after antifungal therapy, as the biomarker CTO and X-ray score correlate well with SUVMAX. PET/CT scan should be considered in case of treatment with corticosteroids, if there is clinical suspicion of recurrence or progress of the disease. CLINICAL IMPLICATIONS: The utility of PET/CT scan is useful for detection of granuloma inflammation. For the follow-up is better than serum markers of inflammation. DISCLOSURE: The following authors have nothing to disclose: Marjeta Tercelj-Zorman, Nadja Koren, Kaja Šifer, Maša Bizjak, Marina Hodolić, Barbara Salobir No Product/Research Disclosure Information

A case highly suspicious of isolated cardiac sarcoidosis

A 55-year-old Caucasian male without cardiac history presented with a broad-complex tachycardia of a right ventricular origin (Fig. 1a). After successful electrocardioversion, echocardiography and coronary angiogram showed no significant abnormalities. Electrophysiological examination suggested a right ventricular mid-septal origin of the arrythmia, closely to the HIS bundle. Cardiac MRI (Fig. 1b,c) showed extensive late enhancement at the right ventricular part of the interventricular septum (Fig. 1b) and a focal lesion in the epicardial inferolateral wall (Fig. 1c), both showing high uptake on FDG PET-CT (Fig. 1d). In the laboratory findings, soluble interleukin-2 receptor (sIL-2R), a marker for sarcoidosis, was elevated (5276 pg/ml, normal value <3000 pg/ml), making cardiac sarcoidosis highly likely. FDG PET-CT and examination of skin and eyes showed no signs of extracardiac sarcoidosis and pulmonary sarcoidosis was excluded by high-resolution CT and bronchoalveolar lavage, suggesting a case of isolated cardiac sarcoidosis. The prevalence of cardiac involvement in sarcoidosis varies from 5 % in symptomatic patients to up to 30 % in autopsies [1]. Isolated cardiac sarcoidosis is rare and only described in case series [2]. For diagnosis, multimodality imaging is recommended, including MRI and FDG PET [3]. FDG PET is the modality of choice to examine (extra)cardiac sarcoidosis [4]. Giant cell myocarditis can be considered in the differential diagnosis. However the scan results, elevated sIL-2R, young age and dysrhythmia are typical for cardiac sarcoidosis. A two-chamber implantable cardioverter defibrillator was implanted and prednisolone treatment was started. FDG PET-CT after 3 months showed complete normalisation. Although extremely rare, this case illustrates the possible occurrence of mono-organ localisation of sarcoidosis. Fig. 1 a Electrocardiogram showing a broad-complex tachycardia of 240 beats/min, retrograde P waves and right-axis deviation, suggesting a right ventricular origin. Cardiac MRI shows extensive late enhancement at the right ventricular ...

Correlation of spleen metabolism assessed by 18F-FDG PET with serum interleukin-2 receptor levels and other biomarkers in patients with untreated sarcoidosis.

The objective of our study was to assess the possible relationship between splenic F-18-fluorodeoxyglucose (18F-FDG) uptake and other established biochemical markers of sarcoidosis activity. Thirty treatment-naive sarcoidosis patients were prospectively enrolled in this study. They underwent biochemical laboratory tests, including serum interleukin-2 receptor (sIL-2R), serum C-reactive protein, serum angiotensin-I converting enzyme, and 24-h urine calcium levels, and a whole-body combined 18F-FDG PET/computed tomography (PET/CT) scan as a part of an ongoing study at our institute. These biomarkers were statistically compared in these patients. A statistically significant linear dependence was detected between sIL-2R and log-transformed spleen-average standard uptake value (SUV avg) (R2=0.488, P<0.0001) and log-transformed spleen-maximum standard uptake value (SUV max) (R2=0.490, P<0.0001). sIL-2R levels and splenic size correlated linearly (Pearson's r=0.373, P=0.042). Multivariate linear regression analysis revealed that this correlation remained significant after age and sex adjustment (β=0.001, SE=0.001, P=0.024). No statistically significant associations were detected between (a) any two serum biomarkers or (b) between spleen-SUV measurements and any serum biomarker other than sIL-2R. Our analysis revealed an association between sIL-2R levels and spleen 18F-FDG uptake and size, whereas all other serum biomarkers were not significantly associated with each other or with PET 18F-FDG uptake. Our results suggest that splenic inflammation may be related to the systemic inflammatory response in sarcoidosis that may be associated with elevated sIL-2R levels.

Interleukin-2 Receptor and Angiotensin-Converting Enzyme as Markers for Ocular Sarcoidosis.

PurposeTo study the impact of soluble IL2 receptor (sIL2R), chest x-ray (CxR), and angiotensin-converting enzyme (ACE) as markers for sarcoidosis in uveitis patients.DesignRetrospective study.MethodsSerum concentrations of sIL2R and ACE were measured in patients with active uveitis. Those with elevated sIL2R and /or ACE values were examined for suspected systemic sarcoidosis.Main Outcome MeasureOur main outcome parameters were the specificity and sensitivity of sIL2R, CxR and ACE in screening for ocular sarcoidosis.ResultsWe measured 261 patients with uveitis for sarcoidosis using sIL2R and ACE between January 2008 and November 2011; sarcoidosis was been diagnosed using other tests (e.g. computer tomography, brochoalveolar lavage, biopsy) in 41 of 53 patients with elevated sIL2R values (>639 U/ml) and in one patient with normal sIL2R (582 U/ml). Their mean sIL2R value was 1310 U/ml, extending from 582 to 8659 U/ml. Only 9 patients, however, presented elevated ACE (>82 U/l). Their mean ACE value was 116.4 U/l, ranging from 84.1 to 175.5 U/l. IL2R specificity was 94% with 98% sensitivity. In contrast, ACE had a specificity of 99.5%, but a sensitivity of only 22%; the chest x-ray had a specificity of 100% with 50% sensitivity in detecting sarcoidosis. We observed the entire spectrum of uveitis: sixteen patients suffered from anterior, 8 from intermediate, 16 from posterior, and 2 from panuveitis.ConclusionsAn elevated level of soluble IL2R suggests sarcoidosis with uveitis more convincingly than ACE, making sIL2R a more effective marker parameter for sarcoidosis than ACE or chest x-ray in uveitis patients.

Prognostic markers of sarcoidosis: an analysis of patients from everyday pneumological practice.

Although sarcoidosis is a well-known disease, sarcoidosis patient outcome and the role of prognostic markers in everyday practice have not yet been well described. Therefore, the goal of the present study was to analyse the fate of sarcoidosis patients and the factors influencing the disease's behaviour in routine practice. The study was a retrospective analysis of 306 consecutive patients (181 females and 125 males; median age 45 years) diagnosed with sarcoidosis in the years 2003-2012. Through the use of uniparametric analysis, it was determined that the stage of the disease, organ involvement, CD4/CD8 ratio in the bronchoalveolar lavage fluid (BALF), serum and urine calcium levels, smoking, and pulmonary functions had a significant influence on spontaneous sarcoidosis resolution. Multiparametric analysis revealed that spontaneous resolution was significantly positively influenced by female gender, a less advanced disease stage, a higher CD4/CD8 ratio in the BALF, lymphocytosis in the BALF and normal pulmonary functions at diagnosis. During follow-up, only three patients died. The causes of death were respiratory failure with pneumonia (n = 2) and heart attack caused by sarcoidosis heart involvement (n = 1). The data show sarcoidosis as a disorder with high variability in clinical and laboratory findings but with good general prognosis.

Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis

Sarcoidosis is an immune-mediated multisystem disease characterized by the formation of non-caseating granulomas. The pathogenesis of sarcoidosis is unclear, with proposed infectious or environmental antigens triggering an aberrant immune response in susceptible hosts. Multiple pro-inflammatory signaling pathways have been implicated in mediating macrophage activation and granuloma formation in sarcoidosis, including IFN-γ/STAT-1, IL-6/STAT-3, and NF-κB. It is difficult to distinguish sarcoidosis from other granulomatous diseases or assess disease severity and treatment response with histopathology alone. Therefore, development of improved diagnostic tools is imperative. Herein, we describe an efficient and reliable technique to classify granulomatous disease through selected gene expression and identify novel genes and cytokine pathways contributing to the pathogenesis of sarcoidosis. We quantified the expression of twenty selected mRNAs extracted from formalin-fixed paraffin embedded (FFPE) tissue (n=38) of normal lung, suture granulomas, sarcoid granulomas, and fungal granulomas. Utilizing quantitative real-time RT-PCR we analyzed the expression of several genes, including IL-6, COX-2, MCP-1, IFN-γ, T-bet, IRF-1, Nox2, IL-33, and eotaxin-1 and revealed differential regulation between suture, sarcoidosis, and fungal granulomas. This is the first study demonstrating that quantification of target gene expression in FFPE tissue biopsies is a potentially effective diagnostic and research tool in sarcoidosis.