TRANSFORMING GROWTH FACTOR 1 IN CHILDREN OF EARLY AGE WITH LIVER TRANSPLANTATION

Transforming growth factor β1 (TGF-β1) plays a key role in the development of the immune response, as well as in the process of liver regeneration. Measuring the level of TGF-β1 may have important clinical implications in liver transplantation, because cytokine concentration in the tissue and in blood plasma varies with different liver diseases.

Aim. To analyze the dynamics of TGF-β1 levels in children-recipients with liver transplant from related donors, including from incompatible blood groups.

Materials and methods. The study involved 127 children aged 3 to 72 months (median – 8, average age – 12 ± 14 months), including 57 boys and 70 girls, with liver cirrhosis, developed as the result of congenital and hereditary diseases of the hepatobiliary system. All patients underwent transplantation of the left lateral liver sector from living related donors: 98 patients were transplanted
fragment of a liver from identical or AB0-compatible donors and 29 – from incompatible donors. The concentration of TGF-β1 was determined by enzyme immunoassay method in blood plasma samples.

Results. Average level of TGF-β1 in blood plasma of children with liver cirrhosis, developed as the result of congenital and hereditary diseases of the hepatobiliary system was 5,2 ± 5,5 ng/ml. A month after liver transplantation from a related donor level of TGF-β1 in blood plasma of recipients increased to 8,1 ± 9,6 ng/ml. One year after transplantation, the average level of TGF-β1 in the recipients of liver fragment was 7,7 ± 8,4 ng/ml, and signifi cantly (p = 0,00) differed from the level prior to transplantation. No association between TGF-β1 level in a month and a year after transplantation and the compatibility of the recipient with AB0 donor was found. A correlation (r = –0,23, p < 0,05) between level of TGF-β1 prior to transplantation and the development of graft dysfunction was observed: in recipients with graft dysfunction (16 cases) cytokine level prior to surgery was lower (p = 0,047) than in other recipients.

Conclusion. Liver transplantation leads to a signifi cant increase in the level of TGF-β1 in the blood plasma of children and that level is not different in recipients after transplantation of a liver fragment from AB0-compatible and AB0-incompatible donors and in recipients with anti-group antibodies before and/or after transplantation, and without them.

1. Готье СВ. Очерки клинической трансплантологии. М.: Триада, 2009: 360. Gautier SV (ed.). Ocherki klinicheskoi transplantologii. M.: Triada, 2009: 360. [In Rus].

2. Shevchenko OP, Tsirulnikova OM, Gichkun OE, Kurabekova RM, Ammosov AA, Gautier SV. Plasma levels of soluble CD30 and CD40L in pediatric patients after liver transplantation. Advances in Clinical Chemistry and Laboratory Medicine. 2012: 124–127.

3. Briem-Richter A , Leuschner A, Krieger T, Grabhorn E, Fischer L, Nashan B et al. Peripheral blood biomarkers for the characterization of alloimmune reactivity after pediatric liver transplantation. Pediatr Transplant. 2013; 17 (8): 757–764.

4. Li MO, Wan YY, S anjabi S, Robertson AK, Flavell RA. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 2006; 24: 99–146.

5. Valva P, Casciato P, Diaz Carrasco JM, Gadano A, Galdame O, Galoppo MC et al. The role of serum biomarkers in predicting fi brosis progression in pediatric and adult hepatitis C virus chronic infection. PloS one. 2011; 6 (8): 17.

6. Kang LI, Mars WM, Michalopoulos GK. Signals and cells involved in regulating liver regeneration. Cells. 2012; 1 (4): 1261–1292.

7. Blobe GC, Schieman n WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med. 2000; 342 (18): 1350–1358.

8. Li MO, Wan YY, Flav ell RA. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity. 2007; 26 (5): 579–591.

9. Rosensweig JN, Omori M, Page K, Potter CJ, Perlman EJ, Thorgeirsson SS et al. Transforming growth factor-beta1 in plasma and liver of children with liver disease. Pediatr Res. 1998; 44 (3): 402–409.

10. Freeman RB, Jr., Wie sner RH, Roberts JP, McDiarmid S, Dykstra DM, Merion RM. Improving liver allocation: MELD and PELD. Am J Transplant. 2004; 9: 114–131.

11. Okamoto Y, Gotoh Y, U emura O, Tanaka S, Ando T, Nishida M. Age-dependent decrease in serum transforming growth factor (TGF)-beta 1 in healthy Japanese individuals; population study of serum TGF-beta 1 level in Japanese. Dis Markers. 2005; 21 (2): 71–74.

12. Hussein MH, Hashimoto T, AbdEl-Hamid Daoud G, Kato T, Hibi M, Tomishige H et al. Pediatric patients receiving ABO-incompatible living related liver transplantation exhibit higher serum transforming growth factor-beta1, interferon-gamma and interleukin-2 levels. Pediatr Surg Int. 2011; 27 (3): 263–268.

13. Kanzler S, Baumann M, S chirmacher P, Dries V, Bayer E, Gerken G et al. Prediction of progressive liver fi brosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta. J Viral Hepat. 2001; 8 (6): 430–437.

14. Lebensztejn DM, Sobaniec -Lotowska M, Kaczmarski M, Werpachowska I, Sienkiewicz J. Serum concentration of transforming growth factor (TGF)-beta 1 does not predict advanced liver fi brosis in children with chronic hepatitis B. Hepatogastroenterology. 2004; 51 (55): 229–233.

15. Chari RS, Price DT, Sue S R, Meyers WC, Jirtle RL. Down-regulation of transforming growth factor beta receptor type I, II, and III during liver regeneration. Am J Surg. 1995; 169 (1): 126–131.

16. Russell WE, Coffey RJ, Jr. , Ouellette AJ, Moses HL. Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. Proc Natl Acad Sci U S A. 1988; 85 (14): 5126–5130.

17. Charles R, Chou HS, Wang L, Fung JJ, Lu L, Qian S. Human hepatic stellate cells inhibit T-cell response through B7-H1 pathway. Transplantation. 2013; 96 (1): 17–24.