The selective biomarker IL-8 identifies IFTA after kidney transplantation in blood cells.

ABSTRACT

Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may serve as diagnostic tools but studies with high patient numbers and differential groups are rare. We validated the potential value of several markers on mRNA level in blood cells and serum protein level in 166 samples from kidney transplanted patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection (UTI), IFTA, antibody-mediated rejection (ABMR), and T-cell-mediated rejection (TCMR) applying RT-PCR and ELISA. The mRNA expression of RANTES, granulysin, granzyme-B, IP-10, Mic-A and Interferon-γ in blood cells did not distinguish specifically between the different pathologies. We furthermore discovered that the mRNA expression of the chemokine IL-8 is significantly lower in samples from IFTA patients than in samples from patients with stable graft function (p<0.001), ABMR (p<0.001), Borderline (BL) TCMR (p<0.001), tubulo-interstitial TCMR (p<0.001) and vascular TCMR (p<0.01), but not with UTI. Serum protein concentrations of granzyme-B, Interferon-γ and IL-8 did not differ between the patient groups, RANTES concentration was significantly different when comparing UTI and ABMR (p<0.01), whereas granulysin, Mic-A and IP-10 measurement differentiated ongoing rejection or IFTA processes from stable graft function but not from each other. The measurement of IL-8 mRNA in blood cells distinguishes clearly between IFTA and other complication after kidney transplantation and could easily be used as diagnostic tool in the clinic.