CHEMOKINE MARKERS ASSOCIATED WITH EARLY REJECTION OF KIDNEY ALLOGRAFT

It is known at the present time that immunological biomarkers may become more sensitive, non-invasive methods of graft rejection diagnosis than those currently used. A growing amount of studies in animal models shows that chemokines, as active participants in the immune process, may be used to this purpose. Our earlier studies have shown an important prognostic significance of IL-6, IL-2, 17A and IL-1RA increase in pre-operative period as markers of acute kidney allograft rejection. When assessing changes in studied peripheral blood growth factors, we concluded that a sharp decrease in BDNF content is a diagnostically significant early sign of kidney allograft rejection. The aim of this study was to identify the prognostic role of serum chemokine levels at the preoperative stage, taking into account the production of anti-HLA antibodies during the post-transplant period as a risk factor of kidney allograft rejection. A comparative analysis of chemokine serum concentrations was performed in the patients with terminal-stage chronic kidney disease (CKD). In the patients from main clinical groups, the blood cytokine levels were measured 6 hours before transplantation, i.e., Eotaxin (CCL11), GRO-α (CXCL1), IL-8 (CXCL8), IP-10 (CXCL10), MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), SDF-1α (CXCL12), RANTES (CCL5), MIG (CXCL9) by means of multiplex immunological assays, using appropriate test systems. The studies have shown significant changes in several chemokines in the CKD patients compared to age-matched controls. However, the following diagnostically significant biomarkers associated with early rejection of transplanted kidney should be considered: increased concentration of CCL2 and CCL4 chemokines, as well as an acute decrease in CCL11. Significantly decreased CXCL12 concentration in peripheral blood could be considered a marker of favorable posttransplant clinical course.  Occurence of HLA antibodies in recipients is also associated with elevated serum levels of CXCL8, CXCL10, CCL4, and CCL5.

1. Alekseev A.V., Gilmanov A.Zh., Gatiyatullina R.S., Rakipov I.G. Recent biomarkers of acute renal injury. Prakticheskaya meditsina = Practical Medicine, 2014, no. 3 (79). (In Russ.)

2. Fedorenko T.V., Kolesnikova N.V., Filippov E.F. Early interleukin markers of acute risk of renal transplantation. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2017, Vol. 11, no. 3, pp. 541- 543. (In Russ.)]

3. Fedorenko T.V., Kolesnikova N.V., Filippov E.F. Growth factors – predictors of acute kidney transplant rejection. Molekulyarnaya meditsina = Molecular Medicine, 2018, pp. 376-377. (In Russ.)

4. Abe T., Su C. A., Iida S. et al. Graft‐Derived CCL2 Increases Graft Injury During Antibody‐Mediated Rejection of Cardiac Allografts. American Journal of Transplantation. – 2014. – Vol. 14. – no. 8. – pp. 1753-1764.

5. Amrouche L., Desbuissons G., Rabant M. et al. MicroRNA-146a in human and experimental ischemic AKI: CXCL8-dependent mechanism of action. Journal of the American Society of Nephrology – 2017. – Vol. 28. – no. 2. – pp. 479-493.

6. Asosingh, K., Vasanji A., Tipton A. et al. Eotaxin-rich proangiogenic hematopoietic progenitor cells and CCR3+ endothelium in the atopic asthmatic response. The Journal of Immunology. – 2016. – Vol. 196. – no. 5. – pp.2377-2387.

7. Burk S. J., Lu D., Sparer T. E. NF-κB and STAT1 control CXCL1 and CXCL2 gene transcription. American Journal of Physiology-Endocrinology and Metabolism. – 2013. – Vol. 306. – no. 2. – pp. E131-E149.

8. Dosanjh A. Activation of Eosinophil CCR3 Signaling and Eotaxin Using a Bioinformatics Analysis of a Mouse Model of Obliterative Airway Disease. Journal of Interferon & Cytokine Research. – 2014. – Vol. 34. – no. 7. – pp. 543-546.

9. Lee C. M., Peng H. H., Yang P. et al. CC Chemokine Ligand-5 is critical for facilitating macrophage infiltration in the early phase of liver ischemia/reperfusion. Scientific Reports. – 2017. – Vol. 7. – no. 1. – P. 3698.

10. Liu B., Li J., Yan L. N. Chemokines in chronic liver allograft dysfunction pathogenesis and potential therapeutic targets. Clinical and Developmental Immunology. – 2013. – Vol. 2013. Article ID 325318, 15 pages.

11. Sigdel T. K., Sarwal M. M. Recent advances in biomarker discovery in solid organ transplant by proteomics. Expert review of proteomics. – 2011. – Vol. 8. – no. 6. – pp. 705-715.

12. Zhuang J., Shan Z., Ma T. et al. CXCL9 and CXCL10 accelerate acute transplant rejection mediated by alloreactive memory T cells in a mouse retransplantation model. Experimental and therapeutic medicine. – 2014. – Vol. 8. – no. 1. – P. 237-242.