Background: The prognostic role of intimal arteritis of kidney allografts in donor-specific antibody negative (DSA-) antibody-mediated rejection (ABMR) remains unclear. Methods: Seventy-two out of 881 patients who had undergone kidney transplantation from 2014 to 2017 exhibited intimal arteritis in biopsies performed during the first 12 months. In 26 DSA negative cases, the intimal arteritis was accompanied by tubulointerstitial inflammation as part of T cell-mediated vascular rejection (TCMRV, N = 26); intimal arteritis along with microvascular inflammation occurred in 29 DSA negative (ABMRV/DSA-) and 19 DSA positive cases (ABMRV, DSA+, N = 17). In 60 (83%) patients with intimal arteritis, the surveillance biopsies after antirejection therapy were performed. Hundred and two patients with non-vascular ABMR with DSA (ABMR/DSA+, N = 55) and without DSA (ABMR/DSA-, N = 47) served as controls. Time to transplant glomerulopathy (TG) and graft failure were the study endpoints. Results: Transplant glomerulopathy -free survival at 36 months was 100% in TCMRV, 85% in ABMR/DSA-, 65% in ABMRV/DSA-, 54% in ABMR/DSA+ and 31% in ABMRV/DSA+ (log rank p < 0.001). Death-censored graft survival at 36 months was 98% in ABMR/DSA-, 96% in TCMRV, 86% in ABMRV/DSA-, 79% in ABMR/DSA+, and 64% in ABMRV/DSA+ group (log rank p = 0.001). In surveillance biopsies, the resolution of rejection was found in 19 (90%) TCMRV, 14 (58%) ABMRV/DSA-, and only 4 (27%) ABMRV/DSA+ patients (p = 0.006). In the multivariable model, intimal arteritis as part of ABMR represented a significant risk for TG development (HR 2.1, 95% CI 1.2-3.8; p = 0.012) regardless of DSA status but not for graft failure at 36 months. Conclusions: Intimal arteritis as part of ABMR represented a risk for early development of TG regardless of the presence or absence of DSA. Intimal arteritis in DSA positive ABMR represented the high-risk phenotype.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Inflammatory aortic diseases are broadly classified into three categories according to the degree of inflammation: atherosclerosis, atherosclerosis with excessive inflammation, and aortitis/periaortitis. This paper presents a case of a 39-year old man with aneurysmal dilatation of thoracic aorta and aortic valve insufficiency. The aortic wall showed thickening and wrinkled "tree bark" appearance as well as apparent scarring of the intima. Histological examination revealed intimal hyperplasia, a granulomatous/giant cell pattern in the inner tunica media, a few epithelioid macrophages, abundant chronic lymphoplasmacytic and histiocytic inflammation and discrete fibrinoid necrosis. The histological findings were indicative of Horton's disease, but no typical clinical features were present. The case illustrates the difficulties involved in diagnosing inflammatory aortic diseases where it may be challenging to arrive at a specific diagnosis despite the knowledge of medical history, and available macroscopic and histological findings.

• MeSH
• aneurysma hrudní aorty patologie   MeSH
• aorta patologie   MeSH
• aortální insuficience patologie   MeSH
• aterosklerotický plát patologie   MeSH
• dospělí MeSH
• dysfunkce levé srdeční komory etiologie   MeSH
• fibróza patologie   MeSH
• hyperplazie MeSH
• lidé MeSH
• makrofágy patologie   MeSH
• myokard patologie   MeSH
• nemoci koronárních tepen patologie   MeSH
• obrovskobuněčná arteritida patologie   MeSH
• tunica media patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n=6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n=4) and non-rejection histologic findings (n=8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n=12) and TCMRV (n=8) samples. The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.

• MeSH
• alografty MeSH
• arteritida genetika   MeSH
• dospělí MeSH
• genová ontologie MeSH
• lidé MeSH
• průřezové studie MeSH
• rejekce štěpu diagnóza   genetika   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• studie případů a kontrol MeSH
• transkriptom * MeSH
• transplantace ledvin metody   MeSH
• tunica intima metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

While the detrimental impact of the humoral acute vascular rejection (AVR) phenotype is recognized, the prognostic significance of isolated v-lesion (IV) remains unclear. In this retrospective single-centre study, AVR was found in 98 of 1015 patients (9.7%) who had undergone kidney transplantation in 2010-2014, with donor-specific antibodies (DSA) evaluated in all of them. The outcome of four AVR phenotypes was evaluated during median follow-up of 59 months; in 25 patients with IV, 18 with T-cell-mediated vascular rejection (TCMVR), 19 with antibody-mediated vascular rejection (AMVR) and 36 with suspected antibody-mediated rejection (sAMVR). AVR was diagnosed mainly by for-cause biopsy (81%) early after transplantation (median 19 POD) and appeared as mild-grade intimal arteritis. IV occurred in low-sensitized patients after the first transplantation (96%) in the absence of DSA. IV responded satisfactorily to treatment (88%), showed no persistence of rejection in surveillance biopsy, and had stable graft function, minimal proteinuria and excellent DCGS (96%). Contrary to that, Kaplan-Meier estimate of 3-year DCGS of AMVR was 66% (log-rank = 0.0004). Early IV represents a benign phenotype of AVR with a favourable outcome. This study prompts further research to evaluate the nature of IV before considering any change in the classification and management.

• MeSH
• biopsie MeSH
• časové faktory MeSH
• dospělí MeSH
• fenotyp MeSH
• HLA antigeny imunologie   MeSH
• imunosupresiva MeSH
• Kaplanův-Meierův odhad MeSH
• ledviny imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• přežívání štěpu MeSH
• protilátky imunologie   MeSH
• rejekce štěpu imunologie   MeSH
• renální insuficience chirurgie   MeSH
• retrospektivní studie MeSH
• riziko MeSH
• T-lymfocyty imunologie   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH