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Biomarkers, monitoring & outcomes

Tuesday September 13, 2022 - 17:35 to 18:35

Room: CF-5

344.8 The plasma level of transforming growth factor beta 1 in heart transplant recipients: relationship with HLA mismatch

Olga Gichkun, Russian Federation

Researcher
Regulatory mechanisms in Transplantology
Shumakov National Medical Research Center of Transplantology and Artificial Organs

Abstract

The plasma level of transforming growth factor beta 1 in heart transplant recipients: relationship with HLA mismatch

Olga Gichkun1,2, Olga Shevchenko1,2, Larisa Makarova1, Natalia Shmerko1, Alex Shevchenko1,2, Sergey Gautier1,2.

1Shumakov National Medical Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation

Introduction: Transforming growth factor beta 1 (TGF-beta1) is a pleiotropic cytokine produced by almost all cells of the body and has multidirectional autocrine and paracrine effects. Current research indicates a possible role for TGF beta1 in the development of cardiac allograft rejection and fibrosis after heart transplantation.

The aim: to evaluate the level and dynamics of TGF-beta1 in patients with chronic heart failure and in cardiac recipients and it is relationship with HLA mismatch.

Methods: 161 patients were examined before and after heart transplantation, aged 49±12 (from 16 to 78) years, 141 (87%) of them were men. Initial diagnosis was dilated cardiomyopathy in 89 (55%) patients. The comparison group consisted of healthy adults (n=12) - liver donors aged 30 ± 6 years, including 5 men (42%). All patients underwent heart transplantation from an identical or AB0 matched donor. Before transplantation, all patients had their blood group determined, and HLA typing of the A, B, DR loci was performed using the polymerase chain reaction. The concentration of TGF beta1 was determined in blood plasma samples before, one month and one year after transplantation by ELISA.

Results: The average plasma level of TGFbeta1 in the patients with terminal heart failure was 27.2± 18.8 ng/ml and was significantly higher than in healthy individuals 8.7 ± 7.5 ng/ml (p= 0.00). The level of TGF-beta1 did not differ in men and women (p=0.7), and did not depend on the initial diagnosis (p=0.27) and blood type (p=0.8). Heart transplantations identical in blood type were performed in 86% of cases, compatible - in 14%. The proportion of mismatch (MM) according to the HLA system was: ММ6=14%, ММ5=35%, ММ4=32%, ММ3=14%, ММ2=5%. One month after heart transplantation, the plasma level of TGF-beta1 decreased to 11.1 ± 7.7 ng/ml (p = 0.00) and did not differ from the amount of MM. A year after transplantation, the plasma level of TGFbeta1 was 10.2 ± 10.5 ng/ml and significantly differed from the level before transplantation (p=0.00). In patients with MM4, the level of TGF beta1 was significantly higher than with MM6 (12.7±11.0 ng/ml vs 5.5±4.5 ng/ml, p=0.048). It was found correlation between plasma level of TGF-beta1 and blood concentration of tacrolimus a year after HTx (r=0.148, p=0.04). However, the plasma level of TGF-beta1 didn’t differ in recipients with and without myocardial fibrosis (p=0.42).

Conclusion: In patients with chronic heart failure the plasma concentration of TGF-beta1 is higher than in healthy individuals, and significantly decreases in recipients after heart transplantation. A relationship was found between the level of TGFbeta1 and the amount of MM, which requires further research.

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