scholarly journals Immunological monitoring in cardiac allograft vasculopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Alyaydin ◽  
H Welp ◽  
R Pistulli ◽  
A Dell Aquila ◽  
J Sindermann ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Absolute Count ◽  
Allograft Vasculopathy ◽  
Group 2

Abstract Background The interaction of immunological determinants and classic cardiovascular risk factors can accelerate the development of cardiac allograft vasculopathy (CAV) with deleterious consequences for the graft function in heart transplantation (HTx). When it comes to immunological risk assessment, inverse CD4/CD8 ratio can be a poor prognostic marker in coronary artery disease, but its influence is unclear in CAV. Aim To evaluate the role of the T-lymphocyte count in peripheral blood as well as CD4/CD8 ratio as a predictive marker for CAV severity in a very long-term follow-up after HTx. Methods We performed a retrospective analysis of patient data collected during routine clinical follow-up visits. These data included innate and adaptive immune cell count in peripheral blood (lymphocyte count, CD3+, CD4+, CD8+ and CD19+ T cells and NK cells). Results The study population consisted of 174 patients with a mean follow-up of 13.1±6.5 years and a mean age at the time of HTx of 45.2±15.0 years. CAV was diagnosed in 71 patients (40.8%), more than half of which underwent interventional procedure or surgical therapy (n=40, 56.3%). A comparison of the cytoimmunological profile of patients with no CAV or mild disease (group 1, n=134) vs. with CAV requiring treatment (group 2, n=40), revealed significantly reduced percentage of CD4+ T cells (46.4±11.4% vs. 41.2±9.6%, p=0.01) and elevated percentage of CD8+ T lymphocytes in group 2 (28.3±14.1% vs. 35.8±13.7%, p=0.003). Thus, the CD4/CD8 ratio was altered in therapy requiring CAV (2.3±2.0 vs. 1.5±1.0, respectively, p<0.001). However, we observed no differences in the absolute count of T-helper cells (CD4+ T cells: 692.2±329.2 vs. 653.8±390.5 cells/μL, p=0.54) and cytotoxic T lymphocytes (CD8+ T cells: 474.7±450.2 vs. 600.0±469.0 cells/μL, p=0.13). Further analysis showed no differences regarding lymphocyte count and absolute count or percentage of CD3+ and CD19+ T cells as well as NK cells. Inverse CD4/CD8 ratio (<1) was associated with greater risk for therapy requiring CAV (OR 2.8, 95% CI 1.3 – 5.9, p=0.009) in a univariate logistic regression analysis. Conclusions Decreased CD4+ T cell count along with increased cytotoxic T lymphocyte count resulting in inverse CD4/CD8 ratio is associated with increased CAV severity in HTx. Given the possible interactions with the immunosuppressive agents and prednisolone, monitoring of the cytomimmunological profile can help identify patients at risk and be useful in establishing therapeutic strategies. FUNDunding Acknowledgement Type of funding sources: None.

P5414Factors influencing mortality in a long-term follow-up after heart transplantation; role of immunomonitoring

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Alyaydin ◽  
H Welp ◽  
C Pogoda ◽  
R Pistulli ◽  
H Reinecke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Transplantation ◽  
Body Mass ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Allograft Vasculopathy ◽  
Cox Regression Analysis ◽  
Group 2 ◽  
Group 1

Abstract Background Despite relevant improvements in the last years, increased mortality limits the success of heart transplantation therapy. Although many factors influencing mortality have been identified, the most studies analyzed relatively short follow-up time following heart transplantation. Purpose Therefore, the aim of our present study was to evaluate risk factors for enhanced mortality with emphasis on quantitative changes in immunological blood cells late after heart transplantation. Methods 174 patients with a mean time after heart transplantation of 13.1±6.5 years were retrospectively analyzed using data collected during follow-up visits in our center. Clinical examinations, results of laboratory tests, including immunomonitoring of CD4+, CD8+, CD19+ cells and natural killer cells, ultrasound vessel visualization and coronary angiography were evaluated with respect to the all-cause mortality. Results In patients who were still alive at the time of data analysis (group 1, n=134), glomerular filtration rate, erythrocyte count, hemoglobin and mean corpuscular hemoglobin concentration were significantly increased compared to the group encompassing patients who died before this time point (group 2, n=40) (p<0.05 for all). In contrast, c- reactive protein (CRP), leukocyte count, triglycerides and N-terminal pro-brain natriuretic peptide were significantly decreased in group 1 versus group 2 (p<0.05 for all). In the first group the patients were relevantly less frequently on dialysis, presented lower NYHA classes, later onset of cardiac allograft vasculopathy and received hearts from donors with lower body mass (p<0.05 for all). Additionally, patients from the first group were characterized by significantly higher CD4 and lower CD8 percentages as well as a tendency towards higher CD19 cell count. In a multivariate cox regression analysis CD4 percentage (hazard ratio (HR): 0.454, confidence interval (CI): 0.236–0.871; p=0.018), onset of cardiac allograft vasculopathy (HR: 0.422, CI: 0.190–0.941; p=0.035) and CRP (HR: 0.325, CI: 0.170–0.621; p=0.018) were independent risk factors for increased mortality. Conclusions Increased inflammation, anemia, renal and heart insufficiency, early onset of cardiac allograft vasculopathy, worse functional status and donor associated factors such as higher body mass correlated significantly with enhanced mortality among patients after heart transplantation. In contrast to the early phase following heart transplantation, where the suppression of CD4+ cell number contributes to the decrease in the frequency of acute rejections, aggressive reduction of CD4+ cells by high doses of immunosuppressive agents late after cardiac transplantation may augment risk of mortality. It may be explained due to the creation of a subclinical chronic immunosuppressive condition and potentiation of side effects of immunosuppressive drugs.

Abstract 14944: Elevated Peak Immune Monitoring Early After Transplantation is Associated with Angiographic Cardiac Allograft Vasculopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Richard Cheng ◽  
Babak Azarbal ◽  
Aaron Yung ◽  
Frank Liou ◽  
Jignesh K Patel ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Immune Monitoring ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
P Value ◽  
Operating Characteristics ◽  
Allograft Vasculopathy ◽  
Group 2 ◽  
Group 1

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.

Depletion of recipient CD8+ T cells does not alter the development of cardiac allograft vasculopathy

2001 ◽  
Vol 20 (2) ◽  
pp. 219 ◽  
Author(s):  
W.Y. Szeto ◽  
A.M. Krasinskas ◽  
D. Kreisel ◽  
A.S. Krupnick ◽  
S.H. Popma ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Allograft Vasculopathy

scholarly journals Allograft or Recipient ST2 Deficiency Oppositely Affected Cardiac Allograft Vasculopathy via Differentially Altering Immune Cells Infiltration

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhenggang Zhang ◽  
Na Zhang ◽  
Junyu Shi ◽  
Chan Dai ◽  
Suo Wu ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Heart Transplantation ◽  
Immune Cells ◽  
Allograft Rejection ◽  
Vascular Occlusion ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Allograft Vasculopathy

The role of IL-33/ST2 signaling in cardiac allograft vasculopathy (CAV) is not fully addressed. Here, we investigated the role of IL-33/ST2 signaling in allograft or recipient in CAV respectively using MHC-mismatch murine chronic cardiac allograft rejection model. We found that recipients ST2 deficiency significantly exacerbated allograft vascular occlusion and fibrosis, accompanied by increased F4/80+ macrophages and CD3+ T cells infiltration in allografts. In contrast, allografts ST2 deficiency resulted in decreased infiltration of F4/80+ macrophages, CD3+ T cells and CD20+ B cells and thus alleviated vascular occlusion and fibrosis of allografts. These findings indicated that allografts or recipients ST2 deficiency oppositely affected cardiac allograft vasculopathy/fibrosis via differentially altering immune cells infiltration, which suggest that interrupting IL-33/ST2 signaling locally or systematically after heart transplantation leads different outcome.

A Single-Centre Series of 40 Patients with Bone-Marrow Biopsy-Defined Large Granular Lymphocyte Leukemia; High Rates of Sustained Response to Oral Methotrexate

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3937-3937
Author(s):  
Christopher Fox ◽  
Talha Munir ◽  
Ian Carter ◽  
Sturch Elaine ◽  
Faith Richardson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Gene Rearrangements ◽  
Single Centre ◽  
Oral Methotrexate ◽  
Lgl Leukemia

Abstract Abstract 3937 Large granular lymphocyte (LGL) leukaemia is a rare lymphoproliferation originating in activated cytotoxic CD8+ T cells or occasionally NK cells. Published series incorporating 40 or more patients are few in number with some differences in diagnostic definitions, making comparisons between studies challenging. Investigators have chiefly relied on peripheral blood for diagnosis; typically defined as a persistent excess (>0.5×109/l) of LGLs, associated with monoclonal T-cell receptor (TCR) gene rearrangements by PCR. However, benign monoclonal CD8+T-cell expansions, phenotypically indistinguishable from T-LGL, are well recognised in both healthy elderly individuals and those with autoimmune disease. To-date, reported response rates to oral Methotrexate (MTX) have been in the order of 40–60%, with MTX-failure reportedly occurring in two-thirds of patients after 1 year of follow-up. We studied 40 patients diagnosed with LGL leukemia at Nottingham University Hospitals NHS Trust, UK, between 1990 and 2011. All patients had a persistent (>6 months) large granular lymphocytosis and, importantly, 97.5% (39/40) patients had undergone a bone marrow (BM) biopsy. In all cases an interstitial infiltrate of cytotoxic T cells and/or NK cells, typically demonstrating characteristic linear arrays, established the diagnosis. A majority of patients had correlative peripheral blood PCR studies confirming clonal TCR gene rearrangements in 80%. Although 5 patients had a polyclonal TCR gene, for all such patients the BM findings (>20% LGLs in some cases) together with clinical context (neutropenia, lymphocytosis and 2 cases of pure red cell aplasia (PRCA)) established the diagnosis of LGL leukemia. The median age at diagnosis was 66 years (21–90 years), with an equal sex distribution. The median total lymphocyte count at clinical presentation was 2.7×109/l (0.7–9.4 x109/l) and a lymphocyte count of ≥2×109/l was seen in 27 patients (68%). Thirty patients (75%) were neutropenic at diagnosis (median neutrophil count 0.9 x109/l (range 0.0–6.5 x109/l). In 13 cases neutropenia was accompanied by anemia, thrombocytopenia or both. Rheumatoid factor was positive in 11 of 27 assessable cases (41%), whilst 11 of 40 (28%) had associated autoimmune clinical disorders, including Rheumatoid arthritis (n=6). With a median follow-up for living patients of 3.2 years (range 1.0–15.1 years), 15 patients (38%) have never required treatment. One further patient was already established on MTX at LGL diagnosis. Treatment was not required in any patients who presented with an isolated, asymptomatic lymphocytosis (n=8, 20%). The median time from diagnosis to treatment was 2.1 months; all treatment-requiring patients needed therapy within 6 months of presentation. Treatment was indicated in 24 patients: neutropenia and recurrent infections (n=8); severe neutropenia (n=6); cytopenias associated with other symptoms (mouth ulcers, skin lesions, organomegaly) (n=8); and PRCA (n=2). MTX (10mg/m2, weekly) was employed as first-line therapy (n=9) and after failure of Prednisolone (0.5–1mg/kg) monotherapy (n=7). Amongst 16 MTX-treated patients, 14 (87.5%) achieved a haematological PR (n=6) or CR (n=8) after a median of 2.5 months (1–9 months). (Improvements in quality of response) Continuing responses (haem-PR to CR) were seen up to 2yrs after starting MTX (of MTX). Notably, for the 14 MTX-responders the median duration of response was 6.5 years (0.3–16), censoring for death and drug-cessation due to patient choice. Neither of the 2 patients with PRCA responded to MTX, but Ciclosporin and Fludarabine were effective salvage therapies for MTX-failures. This is one of the largest single-centre series of LGL leukemia reported to-date. The strengths of our study include robust diagnostic evidence of LGL leukemia including BM biopsy and a long follow-up duration. By contrast to the published data, we describe high rates of response to MTX in both steroid-exposed and naive patients. Time to response exceeded 4 months in some cases and responses were sustained for >5 years in a majority of patients. The role of MTX in LGL leukemia warrants further study. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Donor CD4 T Cells Contribute to Cardiac Allograft Vasculopathy by Providing Help for Autoantibody Production

2009 ◽  
Vol 2 (4) ◽  
pp. 361-369 ◽  
Author(s):  
Thet Su Win ◽  
Sylvia Rehakova ◽  
Margaret C. Negus ◽  
Kourosh Saeb-Parsy ◽  
Martin Goddard ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Autoantibody Production ◽  
Allograft Vasculopathy
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