P686 Expression of CD39 ectonucleotidase on regulatory T cells and on T helper 17 cells in children with IBD receiving anti-TNF therapy

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S558-S559
Author(s):  
S V Petrichuk ◽  
Т Radygina ◽  
A Illarionov ◽  
D Kuptsova ◽  
A Potapov ◽  
...  

Abstract Background CD39, CD73 ectonucleotidases convert extracellular ATP (eATF) to adenosine. eATF is known to have pro-inflammatory activity, and adenosine has anti-inflammatory activity. It was shown decreasement CD39 expression on regulatory T lymphocytes (Treg) during exacerbation in adult patients with IBD. The aim of this study was to evaluate the expression of CD39 on Treg and Th17 lymphocytes (Th17) in children with inflammatory bowel diseases (IBD) with different responses to anti-TNF therapy. Methods The study included 68 children with IBD (CD 35 patients, UC 33 patients) aged 4–18 years with duration of the disease from 6 months till 15 years. All patients were treated with anti-TNF (infliximab, adalimumab) during 11–86 weeks. Clinical response was evaluated according to PUCAI (UC) and PCDAI (CD) scores. Group 1 (n = 35) included patients with exacerbation during anti-TNF therapy, in Group 2 (n = 25) patients with sustained remission. The expression of CD39 on Treg (CD3CD4CD25CD127low) and Th17 cells (CD3CD4CD161) was determined by flow cytometry (NovoCyte Acea Biosciences, Inc.). Statistical analysis was performed using nonparametric Mann–Whitney test and ROC analysis (SPSS Statistics 20). Results It were observed inflammatory activity increasement according to PUCAI (Med 40 [30–65], p = 0.8 × 10–5) and PCDIA scores (Med 28.8 [15–55], p = 1.2 × 10–5) in Group 1 in comparison with Group 2. The amount of Treg expressing CD39 (Treg CD39) was 6–58% from Treg (6–80 cl/μl), and the amount of Th17 with the CD39 marker (Th17CD39) was 0.5–57% (2–49 cl/μl). A direct correlation was revealed between TregCD39 and Th17CD39 (r=0.55 p = 1 × 10–6). It was shown that the number of TregCD39 and Th17CD39 does not depend on the age of the child. However, with an increase in the duration of the disease, a decrease in the absolute amount of Th17CD39 is observed (r = −0.3, p = 0.016). In patients Group 1 there was a significant reduction of CD39 expression on Treg (p = 0.00002) and on Th17 (p = 0.0009) compared with a Group 2 in both diseases. The dependence of TregCD39 on PUCAI (r = −0.5 p = 0.013) and PCDAI (r = −0.43 p = 0.03) was revealed. ROC analysis showed that the cut-off level for groups 1 and 2 is 31.7% for TregCD39 (AUC=0.77; Se 69%, Sp 68%) and 37 cl/μl (AUC=0.907; Se 88%, Sp 88%). Cut-off level for the absolute amount of Th17CD39 was 21 cl/μl (AUC=0.888; Se 79%, Sp 81%). Conclusion The decreasement in the amount of TregCD39 below 31 cl/μl and Th17CD39 below 21 cl/μl is associated with an exacerbation of the disease. The expression level of ectonucleotidase CD39 on Treg and Th17 in children with IBD receiving anti-TNF therapy is independent of age and allows to differentiate the state of remission and exacerbation.

2021 ◽  
Vol 15 (2) ◽  
pp. 17-22
Author(s):  
A. V. Martynova ◽  
T. V. Popkova ◽  
A. P. Aleksankin ◽  
G. I. Gridneva ◽  
E. V. Gerasimova ◽  
...  

Objective: to evaluate changes in T- and B-lymphocyte subpopulations at different stages of rheumatoid arthritis (RA).Patients and methods. The study included 53 patients with a definite RA diagnosis according to the 2010 ACR/EULAR criteria (mean age 54.2 [47; 62] years). Group 1 included 27 patients (25 women and 2 men) without history of synthetic disease modifying anti-rheumatic drugs (sDMARDs) intake, group 2 included 26 patients (22 women and 4 men) receiving sDMARDs (methotrexate or leflunomide). The control group consisted of 29 healthy volunteers (23 women and 6 men), the median age was 58.5 [53; 62] years. In all participants flow cytofluorometry according to the standard technique with immunophenotyping of T- and B-lymphocytes was performed.Results and discussion. Compared to controls, patients in group 1 who had not previously received sDMARDs showed a transient increase in "switched" memory B-cells, transient B-cells, and plasmablasts, which was not observed in patients of group 2 (on sDMARDs therapy). Patients with advanced RA showed a statistically significant decrease in the absolute and relative number of memory B-cells, the absolute and relative number of "switched" B-lymphocytes, as well as the number of plasmablasts and transient cells. In RA patients, a statistically significant rela tionship was established between the number of swollen joints and the level of plasmablasts (r=0.51), memory cells (r=0.54), and "switched" B-cells (r=0.41), p< 0,05 in all cases. There were no statistically significant changes in other subpopulations of B-lymphocytes and the profile of T-lymphocytes.Conclusion. Changes in the B-lymphocyte profile are characteristic of different stages of RA. At an early stage, there is an increase in the number of transient B-lymphocytes, plasmablasts and plasmocytes, and in the advanced stage, a decrease in the level of certain populations of B-lymphocytes, such as memory B-cells and "switched" B-lymphocytes. It can be assumed that the ineffectiveness of sDMARDs is associated with a change in the population composition of B-lymphocytes, which requires further study.


2021 ◽  
Vol 8 ◽  
Author(s):  
Alessandro Arrigo ◽  
Emanuela Aragona ◽  
Luigi Capone ◽  
Carlo Di Biase ◽  
Rosangela Lattanzio ◽  
...  

Background: Fluocinolone acetonide (FAc) implant represents a long-term strategy for the management of diabetic macular edema (DME). Because of the 3-year duration, the careful monitoring of the intraocular pressure (IOP) is necessary. The main aim of the study was to provide quantitative IOP cutoffs associated with the onset of IOP increases.Methods: The study was retrospectively conducted with 2-year of follow-up. We separately considered eyes with good IOP control (Group 1), eyes requiring IOP-lowering medications (Group 2) and eyes undergoing IOP-lowering surgery (Group 3). The statistical analysis assessed Delta% IOP changes over the 2-year follow-up. ROC analysis was performed to detect significant cutoffs associated with Group 2 and Group 3. IOP changes occurring after a previously administered dexamethasone (DEX) implant were also evaluated.Results: We included 48 eyes (48 patients), stratified as follows: Group 1 (25/48; 52%), Group 2 (19/48; 40%) and Group 3 (4/48; 8%). ROC analysis performed on IOP values detected 2-months later DEX implant showed a mean Delta IOP increase&gt;24% significantly associated with IOP-lowering medications after FAc implant, whereas a mean Delta IOP increase&gt;35% was significantly associated with IOP-lowering surgery after FAc implant. With respect to IOP changes occurred after FAc implant, our ROC analysis showed a mean Delta IOP increase&gt;8% significantly associated with IOP-lowering medications, whereas a mean Delta IOP increase&gt;15% was significantly associated with IOP-lowering surgery. DEX-related IOP changes showed 52% sensitivity and 100% specificity of FAc-related IOP increases.Conclusions: IOP changes provides clinically relevant cutoffs associated with the onset of FAc-related IOP increases.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.V Belokurova ◽  
T.P Gizatulina ◽  
N.Y.U Khorkova ◽  
L.U Martyanova ◽  
T.I Petelina ◽  
...  

Abstract Background The presence of left atrial/left atrial appendage (LA/LAA) thrombus is used as a surrogate marker of potential stroke in patients (pts) with atrial fibrillation (AF). Purpose To assess the role of growth differentiation factor 15 (GDF-15) level, clinical and echocardiographic (EchoCG) data as predictors of LA/LAA thrombus in pts with nonvalvular AF. Methods Out of 158 pts with nonvalvular AF admitted to Cardiology Center for radiofrequency ablation or elective cardioversion in 2019–2020 2 groups were formed according to transesophageal EchoCG results: group 1 included pts without LA/LAA thrombus (n=102, mean age 59.5±6.0 years) and group 2 (n=42, mean age 60.9±8.8 years) – pts with LA/LAA thrombus. Arterial hypertension was found in 93 pts of group 1 (91%) and in 40 pts of group 2 (95%, p=0.42), coronary artery disease - in 53 pts (52%) and 29 pts (69%), respectively (p=0.06). Both groups did not differ in frequency and spectrum of oral anticoagulants administration. General clinical assessment, EchoCG, and laboratory tests were performed, including GDF-15 (pg/ml) levels using Human GDF-15/MIC-1 ELISA kit and NT-proBNP (pg/ml) in blood. Results Pts with LA/LAA thrombus more often had persistent AF, while paroxysmal AF was more common in pts without thrombus. There was a tendency to more significant congestive heart failure in group 2. Mean CHA2DS2-VASc score was higher in pts with LA/LAA thrombus, also there was a tendency to a larger proportion of pts with scores ≥3. According to EchoCG data, sizes and volumes of both atria, right ventricle, end-systolic volume, left ventricular (LV) size, pulmonary artery systolic pressure and LV mass index were higher in group 2; LV ejection fraction (LVEF) was normal in both groups, but it was significantly lower in pts with LA/LAA thrombus: 59.1±5.1 and 64.0±7.3, respectively (p&lt;0.001). GDF-15 and NT-proBNP levels were significantly higher in group 2 compared to group 1: p=0.00025 and p=0.ehab724.048801 respectively. According to ROC analysis cut-off were set at level &gt;935.0 pg/ml for GDF-15 (AUC=0.705, 95% CI 0.609–0.800, p&lt;0.001) and &gt;143 pg/ml for NT-proBNP (AUC=0.759, 95% CI 0.670–0.849, p&lt;0.001). Multivariate logistic regression revealed the following variables as independent predictors of LAAT: GDF-15 &gt;935.0 pg/ml (OR=4.132, 95% CI 1.305–13.084) and LVEF (OR=0.859, 95% CI 0.776–0.951). According to ROC analysis, the model had a good quality: AUC=0.776 (p&lt;0.001), sensitivity was 78.3%., specificity - 78.3%. Conclusion High level of GDF-15 (&gt;935.0 pg/ml) along with lower LVEF are independent predictors of LA/LAA thrombus in pts with nonvalvular AF. FUNDunding Acknowledgement Type of funding sources: None.


Author(s):  
Gary T C Ko ◽  
Juliana C N Chan ◽  
Jean Woo ◽  
Edith Lau ◽  
Vincent T F Yeung ◽  
...  

We examined the reproducibility of oral glucose tolerance tests (OGTT) using the World Health Organization criterion in 212 Chinese subjects (male 149, female 63) who underwent two 75 g OGTTs within a 6-week period. The overall reproducibility was 65.6% (139/212) of which 74 subjects had normal glucose tolerance, 24 had diabetes and 41 had impaired glucose tolerance (IGT) on two occasions. The subjects were divided into three groups [group 1: normal OGTTs on both occasions ( n = 74); group 2: one abnormal OGTT (either diabetes or IGT ( n = 51); group 3: 2 abnormal OGTTs ( n = 87)]. Subjects in group 1 were younger, had lower blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), fasting and 2 h plasma insulin levels, triglyceride, very — low density lipoprotein and apolipoprotein-B concentrations than both groups 2 and 3. Group 2 had similar characteristics as group 3 except for a lower glycated haemoglobin (HbA1c), fasting and 2 h plasma glucose during the two OGTTs. With receiver operating characteristic curve (ROC) analysis, a HbA1c. of 5.3% gave an optimal sensitivity of 70.7% and specificity of 74.3% to predict diabetes as defined by a 2h plasma glucose value ≥ 11.1 mmol/L in the first OGTT. Of the 212 subjects, 73 had HbA1c ≥ 5.3%. The reproducibility of OGTT was 56.2% for these 73 subjects. With ROC analysis, a BMI of 25 kg/m2 gave an optimal sensitivity of 53.7% and specificity of 56.7% to predict diabetes. For the 36 subjects with BMI ≥ 25 kg/m2, the reproducibility of OGTT was 58.3%. Similarly, for the 140 subjects with WHR ≥ 0.9, the reproducibility of OGTT was 57.9%. These findings confirmed the poor reproducibility of OGTT which was not improved even amongst subjects with high HbA1c, BMI or WHR. Furthermore, subjects with one abnormal OGTT, whether reproducible or not, had a higher cardiovascular risk profile compared to subjects who had two normal OGTTs.


2010 ◽  
Vol 47 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Juliana Ripoli ◽  
Sender Jankiel Miszputen ◽  
Orlando Ambrogini Jr ◽  
Luciana de Carvalho

CONTEXT: Ulcerative colitis is an inflammatory bowel disease involving superficial inflammation of the mucosa of the colon, rectum, and anus, sometimes including the terminal ileum. When in clinical activity, the disease is characterized by various daily evacuations containing blood, mucus and/or pus alternating periods of remission. OBJECTIVE: To compare nutritional parameters (dietary, biochemical and anthropometric) among patients with ulcerative colitis followed up on an outpatient basis over a period of 1 year and during periods of intestinal inflammatory activity and remission. METHODS: Sixty-five patients were studied over a period of 1 year and divided into two groups: group 1 with inflammatory disease activity (n = 24), and group 2 without disease activity (n = 41). Anthropometric measures, biochemical parameters, quantitative food intake, and qualitative food frequency were analyzed. RESULTS: A significant reduction in body mass index and weight and in the intake of energy, proteins, lipids, calcium, iron and phosphorus was observed in the group with inflammatory activity (group 1) when compared to the period of clinical remission. The most affected food groups were cereals, legumes, oils, and fats. In contrast, in group 2 significant differences in triceps and sub scapular skin fold thickness, total protein, hemoglobin and hematocrit were observed between the first and final visit. Calcium and vitamin B6 intake, as well as the consumption of legumes, meat and eggs, and sugar and sweets, was significantly higher than on the first visit. CONCLUSION: Patients with ulcerative colitis followed up on an outpatient basis tend to be well nourished. However, the nutritional aspects studied tend to worsen during the period of inflammatory disease activity.


2020 ◽  
Vol 35 (2) ◽  
pp. 89-97
Author(s):  
E. V. Grakova ◽  
K. V. Kopeva ◽  
A. T. Teplyakov ◽  
A. V. Svarovskaya ◽  
O. N. Ogurkova ◽  
...  

Objective: The objective of this study is to assess the role of soluble ST2 (sST2) in developing adverse cardiovascular events (ACE) and fatal outcomes in patients with chronic heart failure (HF) during 18 [12.5; 35.5]-month follow-up period.Results. Depending on the median of baseline sST2 levels, all patients were retrospectively divided into two groups: group 1 enrolled patients with sST2 levels < 31.5 ng/mL (n = 22); and group 2 comprised patients with sST2 levels ≥ 31.5 ng/mL (n = 26). In group 1, the sST2 levels were 27.27 [23.94; 29.23] ng/mL, which was 33.9% higher (p < 0.0000001) than in group 2 (41.28 [34.86; 50.17] ng/mL). ACEs were registered in 9 cases (40.9%) in group 1 and in 17 cases (65.4%) in group 2 (p = 0.025). Based on ROC-analysis, baseline ST2 levels ≥ 33.53 ng/mL were considered a biomarker to predict an unfavorable course of ischemic heart failure during 18 [12.5; 35.5] months of follow-up period with sensitivity of 78.9% and specificity of 62.2% (AUC 0.719; 95% CI 0.562–0.845; p = 0.0059).Conclusion. The baseline sST2 levels may be considered a non-invasive biomarker allowing to predict the development of adverse cardiovascular events (ACE) and fatal outcomes in patients with chronic heart failure (HF) during 18 [12.5; 35.5] months of follow-up in addition to traditional risk factors.


Kardiologiia ◽  
2021 ◽  
Vol 61 (11) ◽  
pp. 77-88
Author(s):  
E. V. Grakova ◽  
A. V. Yakovlev ◽  
S. N. Shilov ◽  
E. N. Berezikova ◽  
K. V. Kopeva ◽  
...  

Aim      To study the role of soluble ST2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), and С-reactive protein (CRP) in patients with chronic heart failure and preserved left ventricular ejection fraction (CHF with pLVEF) and syndrome of obstructive sleep apnea (SOSA) in stratification of the risk for development of cardiovascular complications (CVC) during one month of a prospective observation.Material and methods  The study included 71 men with SOSA with an apnea/hypopnea index (AHI) >15 per hour, abdominal obesity, and arterial hypertension. Polysomnographic study and echocardiography according to a standard protocol with additional evaluation of left ventricular myocardial fractional changes and work index were performed for all patients at baseline and after 12 months of observation. Serum concentrations of sST2 , NT-proBNP, and CRP were measured at baseline by enzyme-linked immunoassay (ELISA).Results The ROC analysis showed that the cutoff point characterizing the development of CVC were sST2 concentrations ≥29.67 ng/l (area under the curve, AUC, 0.773, sensitivity 65.71 %, specificity 86.11 %; p<0.0001) while concentrations of NT-proBNP (AUC 0.619; p=0.081) and CRP (AUC 0.511; р=0.869) were not prognostic markers for the risk of CVC. According to data of the ROC analysis, all patients were divided into 2 groups based on the sST2 cutoff point: group 1 included 29 patients with ST2 ≥29.67 ng/l and group 2 included 42 patients with ST2 <29.67 ng/l. The Kaplan-Meyer analysis showed that the incidence of CVC was higher in group 1 than in group 2 (79.3 and 28.6 %, respectively, p<0.001). The regression analysis showed that adding values of AHI and left ventricular myocardial mass index (LVMMI) to sST2 in the model increased the analysis predictive significance.Conclusion      Measuring sST2 concentration may be used as a noninvasive marker for assessment of the risk of CVC development in patients with CHF with pLVEF and SOSA within 12 months of observation. Adding AHI and LVMMI values to the model increases the predictive significance of the analysis. 


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Gombozhapova ◽  
Y Rogovskaya ◽  
M Rebenkova ◽  
J Kzhyshkowska ◽  
V Ryabov

Abstract Introduction The functional characteristics of tissue macrophages associated with the progression of cardiac fibrosis in clinic are still unknown. Purpose The purpose was to study cardiac macrophage phenotypes contributing to the development of chronic inflammation and fibrosis in patients with myocardial infarction (MI). Methods The study included 41 patients with fatal MI type 1. Group 1 (n=24) comprised patients who died within 72 hours of MI (the inflammatory phase) and group 2 (n=17) comprised patients who died 4–28 days after MI (the regenerative phase). Macrophage infiltration (number of cells) in the heart was assessed by double immunofluorescence in the non-infarct area. Each area was evaluated in 20 random fields. We used CD163, CD206, stabilin-1, α-smooth muscle actin (α-SMA), interleukin-10 (IL-10) as markers of M2-like macrophages. Results The number of CD163+/CD206− (p=0.087) and CD163+/206+ (p=0.072) macrophages was higher during the regenerative phase of MI. The number of CD163-/CD206+, stabilin-1+/α-SMA-, stabilin-1+/α-SMA+, stabilin-1+/IL-10−, stabilin-1+/IL-10+, stabilin-1-/IL-10+ did not significantly change throughout the entire period of MI. The comparison of various M2 macrophage subpopulations into groups revealed following. In group 1 the number of CD163+/CD206− and CD163+/CD206+ cells prevailed over CD163−/CD206+ (p=0.033 and p=0.003, respectively), stabilin1+/α-SMA− cells over stabilin-1+/α-SMA+ (p<0.001), and stabilin-1+/IL-10+ cells over stabilin-1+/IL-10− (p=0.018). In group 2 the quantity of stabilin-1+/α-SMA− macrophages prevailed over stabilin-1+/α-SMA+ (p=0.005) and stabilin-1+/IL-10+ over stabilin-1−/IL-10+ (p=0.028). In group 1 the number of CD163+/CD206+ cells correlated with the absolute and the relative number of peripheral blood monocytes prior to the onset of death (R=0.97), while the quantity of stablin-1+/α-SMA+ cells correlated with the absolute number of peripheral blood monocytes at admission (R=-0.53). In group 2 the quantity of CD206+/CD163− cells correlated with the absolute and the relative number of monocytes in the peripheral blood at admission (R=0.73 and R=0.59, respectively), the quantity of CD163+/CD206− macrophages with the incidence of recurrent MI (R= 0.54), and the number of stabilin-1+/α-SMA+ macrophages with the age of patients (R=-0.58). Conclusions We have suggested that the key cardiac macrophage phenotypes contributing to the development of chronic inflammation and cardiac fibrosis in the regenerative phase of MI were stabilin-1+/α-SMA− and stabilin-1+/IL-10+. We revealed subpopulation of stabilin-1+/α-SMA+ macrophages, that indicated the possibility of cellular transdifferentiation and macrophage plasticity. Thus, our results supports that understanding the role of macrophages in initiation, progression, and resolution of cardiac fibrosis is one of the most promising goal in the design of anti-fibrotic treatment strategies for patients with MI.


Kardiologiia ◽  
2021 ◽  
Vol 61 (7) ◽  
pp. 44-54
Author(s):  
T. P. Gizatulina ◽  
N. Yu. Khorkova ◽  
L. U. Martyanova ◽  
T. I. Petelina ◽  
E. V. Zueva ◽  
...  

Aim    To study the role of blood concentration of growth differentiation factor 15 (GDF-15) as a predictor of left atrial/left atrial appendage (LA/LAA) thrombosis in patients with nonvalvular atrial fibrillation (AF).Material and methods    538 patients with nonvalvular AF were admitted to the Tyumen Cardiology Research Center in 2019–2020 for radiofrequency ablation and elective cardioversion. According to findings of transesophageal echocardiography (EcoCG), 42 (7.8%) of these patients had LA/LAA thrombosis and 79 (14.7%) of them had the effect of spontaneous echo contrast (SEC). This comparative, cross-sectional, cohort study included at the initial stage 158 successively hospitalized patients with nonvalvular AF: group 1 (with LA/LAA thrombosis, n=42) and group 2 (without LA/LAA thrombosis and without SEC, n=116). To eliminate significant differences in age between the groups, an additional inclusion criterium was introduced, age from 45 to 75 years. Finally, 144 patients were included into the study: group 1 (with LA/LAA thrombosis, n=42, mean age 60.9±7.2 years) and group 2 (without LA/LAA thrombosis and without SEC, n=116, mean age 59.5±6.0 years). 93 (91%) patients in group 1 and 40 (95%) patients in group 2 had arterial hypertension (p=0.4168); 53 (52%) and 29 (^(%), respectively, had ischemic heart disease (p=0.0611). The groups did not differ in sex, profile of major cardiovascular diseases, or frequency and range of oral anticoagulant treatment. General clinical evaluation, EchoCG, and laboratory tests, including measurements of blood concentrations of GDF-15 and NT-proBNP, were performed.Results    In the group with LA/LAA thrombosis, 1) persistent AF prevailed whereas paroxysmal AF was more frequently observed in patients without thrombosis; 2) a tendency toward more pronounced chronic heart failure was observed; 3) tendencies toward a high median CHA2DS2‑VASc score and toward a greater proportion of patients with scores ≥3 were observed. According to EchoCG findings, group 1 had higher values of sizes and volumes of both atria and the right ventricle, left ventricular (LV) end-systolic volume and size, pulmonary artery systolic blood pressure, and LV myocardial mass index. LV ejection fraction (EF) was in the normal range in both groups but it was significantly lower for patients with LA/LAA thrombosis, 59.1±5.1 and 64.0±7.3, respectively (p=0.00006). Concentrations of GDF-15 (p=0.00025) and NT-proBNP were significantly higher in group 1 than in group 2 (p=0.000001). After determining the threshold values for both biomarkers using the ROC analysis, two independent predictors of LA/LAA thrombosis were obtained by the stepwise multiple regression analysis: GDF-15 >935.0 pg/ml (OR=4.132, 95 % CI 1.305–13.084) and LV EF (OR=0.859, 95 % CI 0.776–0.951). The ROC analysis assessed the model quality as good: AUC=0.776 (p<0.001), sensitivity 78.3 %, specificity 78.3 %.Conclusion    For patients with nonvalvular AF, both increased GDF-15 (>935.0 pg/ml) and LV EF are independent predictors for LA/LAA thrombosis.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Richard Cheng ◽  
Babak Azarbal ◽  
Aaron Yung ◽  
Frank Liou ◽  
Jignesh K Patel ◽  
...  

Introduction: Early immune monitoring (IM) as measured by adenosine triphosphate release from activated lymphocytes is associated with coronary plaque progression by intravascular ultrasound. Hypothesis: Elevated IM is also associated with angiographic cardiac allograft vasculopathy (CAV). Methods: Patients transplanted between January 2007 and December 2011 with early post-transplant IM assays and annual angiographic follow-up were included. IM score was defined as the peak value of assays performed between two-months to mid-year after transplantation. A receivers operating characteristics (ROC) analysis was performed to determine an optimal IM assay cutoff. International Society of Heart Lung Transplantation CAV grading was used, 1 for mild, 2 for moderate, and 3 for severe. Patients were divided into two groups based on the cutoff score, and freedom from angiographic CAV was compared. Results: 232 patients were included in the analysis. Mean age at transplantation was 56.7 ± 11.8 years and 25.9% were female. Peak IM assays occurred at 104.1 ± 43.7 days after transplantation, with an average of 3.2 ± 1.8 assays measured per patient. A ROC analysis determined an optimal IM assay cutoff of 458 ng ATP/ml. Group 1, n = 178, was defined as having peak IM assays <458 ng ATP/ml. Group 2, n = 54, was defined as having peak IM assays ≥458 ng ATP/ml. Mean peak IM assays for Group 1 and Group 2 were 243.1 ± 115.5 and 592.9 ± 155.5 ng ATP/ml, respectively. Mean clinical and angiographic follow-up were 4.0 ± 1.5 and 3.5 ± 1.6 years, respectively. As demonstrated in Figure 1, CAV1 occurred in 80 of 178 patients (44.9%) in Group 1, and 35 of 54 patients (64.8%) in Group 2, p-value 0.008 (Log Rank). CAV2/3 occurred in 6 of 178 patients (3.4%) in Group 1, and 8 of 54 patients (14.8%) in Group 2, p-value 0.002. Conclusions: Early elevated peak IM is associated with decreased freedom from angiographic CAV and suggests the potential use of IM in the tailoring of immunosuppression regimens for preventing CAV.


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