Antibody-mediated rejection (ABMR) is a major obstacle to the long-term success in kidney transplantation. Diagnosis of ABMR is determined according to the internationally recognized Banff criteria. However, a significant proportion of patients does not meet all the defined criteria, and the outcome of such cases remains poorly understood. The histology of ABMR frequently lacks sensitivity and specificity. More importantly, mixed forms of ABMR and T cell-mediated rejection as well as findings of nonspecific injury are common in clinical settings. Donor-specific anti-HLA antibodies (DSA) are detectable only in half of the ABMR cases by histology. Prognostic role of non-HLA antibodies against various endothelial proteins has been discussed. Antibody independent NK cell activation reflecting killer-cells’ inhibitory receptor incompatibility is suggested in microvascular inflammation in DSA negative patients. Molecular assessment of ABMR has been prioritized to overcome high interobserver variability and improve diagnostics in mixed forms of rejections and in DSA negative cases. Finally, donor-derived cell-free DNA detected in a recipient’s peripheral blood sample has been proposed as a noninvasive marker for diagnosis of graft rejection, and thus might serve as a liquid biopsy in the near future. Despite all achievements, diagnosing ABMR in kidney allografts remains to be a challenge in a significant number of cases.
Peripheral blood monocytes, which serve as precursors for tissue macrophages and dendritic cells (DC), play a key role in the immune response to kidney allograft, reparation processes and homeostasis regulation. In this prospective study, we used multicolor flow cytometry to monitor the phenotypic patterns of peripheral monocytes in subjects with uncomplicated outcomes and those with acute rejection. We found a reciprocal increase in the proportion of "classical monocytes" (CD14+CD16-) along with a decline in pro-inflammatory "intermediary" (CD14+CD16+) and "non-classical" (CD14lowCD16+) monocytes in subjects with normal outcomes. In subjects with acute rejection, we observed no reduction in "intermediary" monocytes and no increase in "classical" monocytes. Patients with uncomplicated outcomes exhibited downregulated HLA-DR in all three monocyte subpopulations. However, non-classical monocytes were unaffected in subjects with acute rejection. Expression of CD47 was downregulated after transplantation, while patients with antibody-mediated rejection and donor-specific antibodies showed higher pre-transplant values. In monocytes isolated at the time of biopsy, CD47 expression was higher in individuals with acute rejection compared to patients with normal outcomes one year post-transplant. Expression of CD209 (DC-SIGN) and the proportion of CD163+CD206+ subpopulations were upregulated during the first week after kidney transplantation. CD209 was also upregulated in samples taken on the day of biopsy confirming acute rejection. Our data demonstrate that kidney allograft transplantation is associated with phenotypic changes in peripheral blood monocytes during acute rejection., Veronika Švachová, Lenka Krupičková, Marek Novotný, Martina Fialová, Kristýna Mezerová, Eva Čečrdlova, Věra Lánská, Antonij Slavčev, Ondřej Viklický, Ilja Stříž., and Obsahuje bibliografii
Kidney allograft pathology assessment has been traditionally
based on clinical and histological criteria. Despite improvements
in Banff histological classification, the diagnostics in particular
cases is problematic reflecting a complex pathogenesis of graft
injuries. With the advent of molecular techniques, polymerasechain reaction, oligo- and microarray technologies allowed to
study molecular phenotypes of graft injuries, especially acute and
chronic rejections. Moreover, development of the molecular
microscope diagnostic system (MMDx) to assess kidney graft
biopsies represents the first clinical application of a microarraybased method in transplantation. Whether MMDx may replace
conventional pathology is the subject of ongoing research,
however this platform is particularly useful in complex histological
findings and may help clinicians to guide the therapy.
To overcome the shortage of cadaveric kidneys available for transplantation, several countries organize systematic kidney exchange programs. The kidney exchange problem can be modelled as a cooperative game between incompatible patient-donor pairs whose solutions are permutations of players representing cyclic donations. We show that the problems to decide whether a given permutation is not (weakly) Pareto optimal are NP-complete.
Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF- β 1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF- β 1 staining. The data obtained were correlated with plasma TGF- β 1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF- β 1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF- β 1 plasma levels, cyclosporine levels, plasma lipids, HLA- mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF- β 1 tissue expression is linked with chronic vasculopathy., O. Viklický, I. Matl, L. Voska, R. Böhmová, M. Jarešová, J. Lácha, A. Lodererová, I. Stříž, V. Teplan, Š. Vítko., and Obsahuje bibliografii
M2 macrophages expressing CD163 are known to suppress immune responses but have been also found in biopsies of patients with chronic kidney allograft injury associated with interstitial fibrosis. The aim of our study was to evaluate the expression of CD163 in blood monocytes, precursors of tissue macrophages, in kidney allograft recipients with uncomplicated outcome (n=94) compared with those developing acute rejection (n=44). Blood samples were collected before the transplantation and at 1 week, 1 month and 1 year. The expression of CD163 increased during the first week after the transplantation not only in classical (CD14+CD16- ) but also in intermediate (CD14+CD16+) and nonclassical (CD14lowCD16+) monocytes in all patients regardless of their rejection status. In patients developing acute rejection, higher pre-transplant expression of CD163 on blood monocytes was found. In vitro experiments confirmed strong induction of membrane CD163 on monocytes together with CD206 (an alternative marker of M2 macrophages) in response to IL-10. We assume from our data that dramatic upregulation of CD163 by peripheral blood monocytes may have a pathophysiological role in early phases after kidney allograft transplantation and high pre-transplant expression of CD163 on blood monocytes might be involved in events leading to acute rejection., Lenka Čurnová, Kristýna Mezerová, Veronika Švachová, Martina Fialová, Marek Novotný, Eva Čečrdlová, Ondřej Viklický, Ilja Stříž., and Obsahuje bibliografii