Anti-desmoglein2 autoantibodies are present in patients with cardiac sarcoidosis and correlate with cardiac inflammation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
G Suna ◽  
A Kolios ◽  
D Chatterjee ◽  
M Fatah ◽  
A Gasperetti ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Zurich ACM Program is supported by generous grants from the Georg and Bertha Schwyzer-Winniker Foundation, the Baugarten Foundation, Swiss National Science Foundation, Swiss Heart Foundation and Wild Foundation. This work is also supported by a Canadian Institutes of Health Research grant (FRN: 162402) and the Labatt Heart Centre and Waugh Family Innovation Funds, Caitlin Elizabeth Morris Memorial Fund, Alex Corrance Memorial Foundation and Meredith Cartwright. BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) has several phenocopies such as cardiac sarcoidosis (CS), idiopathic outflow tract ventricular tachycardia (OT-VT) and myocarditis. Differentiation between these entities can be challenging. Recently, we have identified diagnostic anti-desmoglein-2 autoantibodies (anti-DSG2 Abs) in patients with ARVC. PURPOSE We sought to examine whether anti-DSG2 Abs are also present in clinical phenocopies of ARVC. METHODS Anti-DSG2 Abs in sera of 25, 19 and 22 patients with sarcoidosis, OT-VT and myocarditis, respectively, were assessed by western blots and ELISA. Clinical and imaging parameters, as well as conventional biomarkers were correlated to detected anti-DSG2 Ab intensity levels. RESULTS Anti-DSG2 Abs, at various intensities, were identified in 6/25 (24%) patients with sarcoidosis, all presenting with CS, but were absent in patients with OT-VT and myocarditis. Cardiac 18F- fluorodeoxyglucose positron emission tomography (18F-FDG PET) was positive in all sarcoidosis patients with positive anti-DSG2 Abs, corresponding to a median PET maximum standardized uptake value (SUVmax) of 5.65 [IQR: 5.15 – 10.9]. In sarcoidosis patients without anti-DSG2 Abs, the SUVmax values were significantly lower with a median of 0 [IQR: 0 – 4] (p = 0.011). The Pearson correlation coefficient (R) was 0.188 (p = 0.039) indicating a positive correlation between cardiac 18F-FDG uptake and anti-DSG2 Abs. No significant correlation was detected for any of the other clinical parameters and biomarkers. CONCLUSIONS In addition to being present in ARVC, anti-DSG2 Abs are also found in CS, a common phenocopy of ARVC; conversely, anti-DSG2 Abs are absent in idiopathic OT-VT and myocarditis. Anti-DSG2 Ab levels positively correlate with myocardial disease activity in CS as indicated by cardiac 18F-FDG PET scanning. Abstract Figure. Central illustration

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Suna ◽  
A Kolios ◽  
D Chatterjee ◽  
M Fatah ◽  
A Gasperetti ◽  
...  

Abstract Introduction Cardiac sarcoidosis (CS) is an inflammatory granulomatous disease of unknown origin. CS and arrhythmogenic right ventricular cardiomyopathy (ARVC) are overlapping syndromes. With both, patients are at increased risk of ventricular arrhythmias and sudden cardiac death. However, the diagnosis of CS is challenging, especially in patients with no extracardiac involvement, but correct diagnosis has large therapeutic impact. Recently, a novel diagnostic autoantibody (anti-DSG2 Ab) was identified in ARVC. We sought to identify this antibody in CS patients and correlate its levels with inflammation activity using cardiac positron-emission-tomography (18-FDG-PET). Methods Recombinant human desmoglein-2 (DSG2) proteins on western blots were exposed to sera as well as purified IgG of 14 patients with sarcoidosis (all confirmed by histology) and 6 controls (1 ARVC patient (positive control) and 5 healthy control subjects (negative control)). Clinical patient characteristics were correlated to detected antibody intensity levels. Results The sarcoidosis cohort comprised 43% (6/14) male patients and the average age was 50±12 years. Anti-DSG2 Abs were identified in 43% (6/14) and were detected faintly (below cut off level) in 21% (3/14) of all sarcoidosis patients. Antibody was also present in the ARVC patient (1/1) and was absent in all control subjects (5/5). Myocardial inflammation was present in 18-FDG PET imaging in all CS patients with positive anti-DSG2 Abs, corresponding to an average SUV (standardized uptake value) of 8.1±4.2. In patients with faint or no antibody, the SUV values were significantly lower with 1.2±2.1 and 3.2±4.0, respectively (P=0.044, one-way ANOVA). The Pearson correlation coefficient (R) was 0.6 (P=0.037) for SUV vs. higher antibody levels assessed by pixel count of the western blot bands for purified IgG. Conclusions Anti-DSG2 Abs are not only a specific biomarker for ARVC, but are also found in CS, suggesting a similar pathophysiological mechanism in these overlapping syndromes, both involving cardiac inflammation and myocyte cell death. Moreover, antibody levels correlate with disease activity on cardiac PET imaging. Larger cohorts are necessary to confirm these findings. Funding Acknowledgement Type of funding source: None


Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 839
Author(s):  
Tzu-Chuan Ho ◽  
Chin-Chuan Chang ◽  
Hung-Pin Chan ◽  
Ying-Fong Huang ◽  
Yi-Ming Arthur Chen ◽  
...  

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: “asymptomatic”, “COVID-19”, “[18F]FDG PET/CT”, and “nuclear medicine” were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.


2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
W Nammas ◽  
S Uotila ◽  
J Teuho ◽  
M Pietila ◽  
J Airaksinen ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can detect arterial inflammation in individuals with atherosclerosis, but the associations among different vascular territories for 18F-FDG uptake are not known. Purpose We explored any possible correlation between arterial inflammation quantified by 18F-FDG PET in the aorta, carotid arteries, and coronary arteries in patients presenting with acute coronary syndrome (ACS), or chronic coronary artery disease (CAD). Methods Prospectively, we performed hybrid computed tomography angiography and 18F-FDG PET in 43 patients (26 ACS and 17 chronic CAD) at 6.6 ± 5.7 days following invasive coronary angiography. 18F-FDG PET was performed 90 minutes after injection of 302.2 ± 28.4 MBq 18F-FDG. Arterial 18F-FDG uptake was measured in the thoracic aorta, carotid arteries, and coronary arteries, and expressed as the target-to-background ratio (TBR; the ratio between arterial maximal standardized uptake value normalized to blood pool mean standardized uptake value) in the whole artery, and in the most diseased segment (MDS). Results Mean age was 64.9 ± 9.1 years, 90.7% males. The whole artery 18F-FDG uptake was higher in the aorta than in the carotid arteries (median TBR 2.23, interquartile range [0.36] vs. 1.88 [0.42], p < 0.001); whereas uptake in the coronary arteries was lower than in the aorta or carotid arteries (1.13 [0.23], p < 0.001 both). Similarly, 18F-FDG uptake in the aortic MDS was higher than in the carotid MDS (2.75 [0.62] vs. 2.25 [0.63], p < 0.001); whereas 18F-FDG uptake in the coronary MDS was the lowest (1.40 [0.33], p < 0.001 both). These findings were consistent in both ACS and chronic CAD patients. The whole artery 18F-FDG uptake of the aorta and carotid arteries correlated in patients with ACS (r = 0.58, p = 0.002), but not in patients with chronic CAD (r = 0.21, p = 0.3). There was no correlation between the whole artery 18F-FDG uptake in the coronary arteries and either the aorta or carotid arteries in the whole cohort (r=-0.16, p = 0.2, r = 0.01, p = 0.9, respectively), in patients with ACS (r = 0.06, p = 0.7, r=-0.01, p = 0.9, respectively), or in those with chronic CAD (r=-0.4, p = 0.1, r=-0.09, p = 0.7, respectively). Conclusions In patients with ACS or chronic CAD, large arteries had higher 18F-FDG uptake than the coronary arteries. The intensity of 18F-FDG uptake in the coronary arteries did not correlate with that in the carotid arteries or the aorta, indicating that disease activity differs between large arteries and coronary arteries.


CNS Oncology ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. CNS46 ◽  
Author(s):  
Meetakshi Gupta ◽  
Tejpal Gupta ◽  
Nilendu Purandare ◽  
Venkatesh Rangarajan ◽  
Ameya Puranik ◽  
...  

Aim: To prospectively assess the clinical utility of pretreatment flouro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with primary central nervous system (CNS) lymphoma (PCNSL). Materials & methods: Patients with suspected/proven PCNSL underwent baseline whole-body 18F-FDG-PET/CT. Maximum standardized uptake value and tumor/normal tissue ratios were compared between CNS lymphoma and other histological diagnoses. Results: The mean maximum standardized uptake value (27.5 vs 18.2; p = 0.001) and mean tumor/normal tissue ratio (2.34 vs 1.53; p < 0.001) of CNS lymphoma was significantly higher than other histologic diagnoses. Five of 50 (10%) patients with biopsy-proven CNS lymphomas had pathologically increased FDG-uptake at extraneuraxial sites uncovering systemic lymphoma. Conclusion: Pretreatment whole-body 18F-FDG-PET/CT provides valuable complementary information in the diagnostic and staging evaluation of patients with PCNSL to guide therapeutic decision-making.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3917-3917
Author(s):  
Sylvain P Chantepie ◽  
Narinée Hovhannisyan ◽  
Stéphane Guillouet ◽  
Alain Manrique ◽  
Oumedaly Reman ◽  
...  

Abstract Introduction: [18 F]-Fludarabine is a promising novel positron emission tomography (PET) radiotracer for lymphoid malignancies. The rationale for its development is the high selectivity of fludarabine uptake within lymphoid cells, irrespective of their cycle activity, and the fluorine atom within the molecule, which is replaced by [18 F] and leads to a positron emitting biomarker. Pre-clinical studies (Dhilly et al, Mol Imaging Biol 2014,16:118-26 ; Hovhannisyan et al, EJNMMI Res 2015,5:23) showed a marked tumor uptake in lymphoma-bearing mice. The aim of this study was to describe anatomical sites with abnormal [18F]-fludarabine uptake in DLBCL patients. This study was designed as a clinical proof of concept. Methods: [18F]-Fludarabine was produced according to a method already described (Guillouet et al, Mol Imaging Biol 2014,16:28-35). [18F]-Fludarabine PET/CT (Discovery RX VCT 64, GE Healthcare) was performed in 5 histologically confirmed and treatment naïve DLBCL patients (65 ± 8 years old). Successive partial body PET scans (skull vertex to mid-thigh) were acquired for 250 min after intravenous injection of [18F]-fludarabine with an activity of 4MBq/kg. PET images were analyzed drawing VOIs over the uptake sites on a late scan and projected onto all co-registered scans of the same subject. The intensity of tracer uptake was evaluated with standardized uptake value (SUVmax). The performance of [18F]fludarabine PET/CT was visually compared with conventional assessments (high-resolution CT) and [18F]-FDG PET. Results: CT and [18F]-FDG PET staging of the 5 patients was I to IV. No adverse event was recorded during and after the procedure. In all 5 patients, the uptake of [18F]-fludarabine coincides with sites expected to be involved following conventional staging. SUVmax were significantly higher in involved sites in comparison with non-lymphoma sites (Figure 1). As previously demonstrated in an animal model, we found no uptake in the cardiac muscle and brain in contrast to [18F]-FDG PET. Bone marrow was histologically normal in the 5 patients and [18F]-fludarabine PET displayed no hypermetabolism. A progressive splenic uptake (x4 to x8 at 250 min) was observed in every patient. The possibility of an unexpected splenic infiltration appears to be a better explanation than uptake by physiologically normal lymphoid tissue. Comparison of [18F]-FDG and [18F]-fludarabine PET showed discrepancies in 2 patients. The first had bilateral hilar [18F]-FDG uptakes (Figure 1C), not present in [18F]-fludarabine PET, which persisted on [18F]-FDG PET after completion of the treatment and disappearance of all suspected pathological sites. This pattern suggests a non-specific [18F]-FDG hypermetabolism. The second patient had a right testis positive [18F]-FDG PET, not evident with [18F]-fludarabine PET. Histology of the testis confirmed the presence of NHL. The interpretation of this would require further extensive data. Conclusion: [18F]-Fludarabine PET/CT appears to be a promising tool to diagnose discordance and follow-up NHL. These preliminary results showed a clear specificity of this novel radiotracer for lymphoma tissues and support the development of this innovative biomarker for lymphoproliferative diseases. Studies for a more detailed comparison with [18F]-FDG PET are in progress. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ikchan Jeon ◽  
Eunjung Kong ◽  
Sang Woo Kim

Abstract Background 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) shows great potential for diagnosis and assessing therapeutic response of tuberculous spondylitis. Tuberculous spondylitis required long-term anti-tuberculosis (TB) medication therapy, and the optimal duration of therapy is controversial. There is still no clear way to tell when the anti-TB therapy can safely be discontinued. Case presentation Three patients with tuberculous spondylitis were evaluated for therapeutic response using 18F-FDG PET/magnetic resonance imaging (MRI). Clinical and hematological improvements were achieved after about 12 months of anti-TB medication therapy, and we considered whether to discontinue the therapy. There was no relapse during one year of follow-up after discontinuation of 12 months anti-TB medication based on the low maximum standardized uptake value (SUVmax) of 1.83 in one patient. However, the other two patients continued further anti-TB medication therapy based on the high SUVmax of 4.14 and 7.02, which were suspected to indicate active residual lesions in the abscess or granulation tissues. Continuous TB was confirmed by the bacterial and histological examinations. Conclusions 18F-FDG PET/MRI has metabolic and anatomical advantages for assessing therapeutic response in TB spondylitis, and can be considered as a helpful independent and alternative method for determining the appropriate time to discontinue anti-TB medication.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masatoyo Nakajo ◽  
Satoko Ojima ◽  
Hirofumi Kawakami ◽  
Atsushi Tani ◽  
Akira Hirayama ◽  
...  

AbstractThe association between 18F-fluorodeoxyglucose (18F-FDG) myocardial uptake and clinical presentations in cardiac sarcoidosis (CS) has not yet been clarified. The Patlak slope, Ki, which represents the rate of 18F-FDG uptake is a quantitative index of 18F-FDG metabolism. This study aims to investigate the usefulness of standardized uptake value (SUV) and Patlak Ki images (Ki images) extracted from dynamic 18F-FDG-PET/CT for evaluating the risk of clinical events (CEs) in CS. The SUV and Ki myocardial images were generated from 30 dynamic 18F-FDG-PET/CT scans of 21 CS patients. The SUV and Ki images both were rated as positive in 19 scans and negative in 11 scans with the same incidence of CEs which were significantly higher in positive than negative scans [cardiac dysfunction: 78.9% (15/19) vs. 27.2% (3/11); arrhythmic events: 65.5% (10/19) vs. 0% (0/11)]. In 19 positive scans, the three Ki parameters (Ki max, Ki mean and Ki volume) were significantly higher in scans for patients with arrhythmic events than in those without. Logistic regression analysis showed that the Ki volume alone was significantly associated with the risk of arrhythmic events. Our study suggests that Ki images may add value to SUV images for evaluating the risk of CEs in CS patients.


2021 ◽  
Author(s):  
Özlem Şahin ◽  
Buğra Kaya ◽  
Zeynep Aydın ◽  
Ahmet Eren Şen ◽  
Mehmet Sinan İyisoy ◽  
...  

Abstract Objective To evaluate whether volumetric PET parameters such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) contributed to maximum standardized uptake value (SUVmax) in predicting prostate carcinoma in the prostate incidentalomas (PI) in 18F-FDG PET/CT. Materials and methods This retrospective study comprised 107 patients with PI of 4723 male patients who had undergone 18F-FDG PET/CT. SUVmax and volumetric PET parameters of PIs were assessed. MTV and TLG were acquired with each SUV threshold as 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0. Results The PI incidence was 2.3%, and the malignancy ratio of PI was 15.9%. According to further analysis results, 17 patients were in the malignant group, and 46 patients were in the benign group. Malignant PIs had higher SUVmax (10.6 vs. 6.4 and p<0.01), MTV (all p < 0.01) and TLG (all p < 0.01) than benign incidentalomas. All volumetric PET parameters had higher area under the curve (AUC) than SUVmax. SUVmax AUC was 0.835 [95% confidence interval (CI): 0.728–0.942]. MTV 2.5 and TLG 2.5 had the highest performance for predicting malignant PI.MTV2.5 AUC was 0.871 (95% CI: 0.775–0.968), and TLG2.5 AUC was 0.882 (95% CI: 0.797–0.967). Using TLG 2.5 greater than 29.8 as the cut-off point, the sensitivity and specificity for malignancy prediction were 94.1% and 82.6%, respectively. Conclusion In this study, in which the effectiveness of volumetric parameters in the diagnosis of PI was evaluated for the first time, it was shown that they could potentially have clinical value along with SUVmax.


2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Liran Domachevsky ◽  
Hanna Bernstine ◽  
Meital Nidam ◽  
Dan Stein ◽  
Natalia Goldberg ◽  
...  

Background. To investigate same day 18F-FDG (Fluorodeoxyglucose) PET (Positron Emission Tomography)/MR (Magnetic Resonance) test-retest repeatability of Standardized Uptake Value measurements normalized for body weight (SUV) and lean body mass (SUL) in different locations in the liver. Methods. This prospective study was IRB approved with written informed consent obtained. 35 patients (20 women and 15 men, 61±11.2 years) that performed a whole-body 18F-FDG PET/MR followed by liver-dedicated contrast-enhanced 18F-FDG PET/MR were included. SUV/L max, mean, and peak were measured inferior to, superior to, and at the right portal vein and in the left lobe of the liver. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated and Bland-Altman plots were obtained. Results. The variability for SUV/L’s measurements was lowest inferior to the portal vein (<9.2%) followed by measurements performed at the level of the portal vein (<14.6%). Conclusion. The area inferior to the portal vein is the most reliable location for hepatic 18F-FDG uptake measurements on PET/MR.


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