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Bela Ivanyi - One of the best experts on this subject based on the ideXlab platform.
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Peritubular Capillary basement membrane multilayering in early and advanced transplant glomerulopathy quantitative parameters and diagnostic aspects
Virchows Archiv, 2016Co-Authors: Dejan Dobi, E Kemeny, Edit Szederkenyi, Pal Szenohradszky, Zsolt Bodo, Laszlo Bidiga, Zoltan Hodi, Aniko Szilvasi, Bela IvanyiAbstract:The ultrastructural quantitative aspects of Peritubular Capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTCcirc). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3). Their respective clinical, serological, and morphological characteristics were then compared. The clinical data revealed that mild TG corresponded to early chronic antibody-mediated rejection (cABMR), while moderate-to-severe TG corresponded to the advanced stage of the disease. The permissive threshold displayed the lowest specificity (73 %) and the highest sensitivity (83 %) for moderate-to-severe TG, and its corresponding PTCcirc value was 3 layers. In contrast, the strict threshold—adopted by the Banff 2013 classification—displayed a specificity and sensitivity of 93 and 52 %, respectively, and the corresponding PTCcirc was 4 layers. In mild TG, 26 % of the cases met the permissive cutoff and 6 % the strict cutoff. Mild TG was associated with a lower PTCcirc (2.6 layers vs 4.5 layers in moderate-to-severe TG; p < 0.0001). Amongst the various criteria, the permissive criterion was associated most frequently with mild TG, and had prognostic relevance. Because of this, we propose its usage as a marker of early cABMR-induced PTCBML if non-alloimmune causes of PTCBML can be ruled out.
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Peritubular Capillary basement membrane changes in chronic renal allograft rejection comparison of light microscopic and ultrastructural observations
Virchows Archiv, 2011Co-Authors: Bela Ivanyi, E Kemeny, Zita Morvay, Pal Szenohradszky, Peter Rago, Norbert Lazar, Krisztina Boda, Edit SzederkenyiAbstract:Marked Peritubular Capillary basement membrane (PTCBM) multilayering, the ultrastructural feature of chronic antibody-mediated rejection (ABMR) of kidney allografts, was found to correspond histologically to PTCs with thickened BMs; such PTCs have been suggested as a novel histological marker of chronic rejection. We investigated whether scoring of PTCBM thickening can substitute the ultrastructural search for PTCBM multilayering. The thickening was graded in PAS- and Jones-stained sections in 110 biopsies from recipients with a late dysfunction, all examined ultrastructurally for transplant capillaropathy (≥3 PTCs with ≥5 BM layers). Grade 0 indicated no thickening. Grade 1 and grade 2 were assigned when the PTCBMs were as thick as or thicker than those of the non-atrophic tubules, and duplication/chain-like lamination of the PTCBM was noted in ≤3 or ≥4 high-power fields, respectively. The series was enrolled in subgroups of those with and those without histopathological lesions of chronic rejection. Fifty-six biopsies displayed lesions of chronic ABMR. Transplant capillaropathy was demonstrated in 40 biopsies. Grade 2 thickening furnished a substantial interobserver concordance rate (κ = 0.803) and correlated with the transplant capillaropathy. Jones staining performed somewhat better in scoring than PAS staining. Grade 2 thickening was verified in 35 biopsies involving chronic ABMR, and in one control biopsy (sensitivity 61.4%, specificity 0.98). Grade 1 thickening was not suggestive of chronic ABMR at all. In conclusion, grade 2 thickening can be regarded as the histopathological lesion of chronic ABMR; however, electron microscopy remains the gold standard in the assessment of PTCBM changes.
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Peritubular Capillary damage in acute humoral rejection an ultrastructural study on human renal allografts
American Journal of Transplantation, 2005Co-Authors: Peter Liptak, E Kemeny, Zita Morvay, Edit Szederkenyi, Pal Szenohradszky, F Marofka, J Toldi, M Exner, Bela IvanyiAbstract:The ultrastructural features of Peritubular Capillary (PC) damage was studied in 12 kidney allografts with acute humoral rejection (AHR). AHR manifested in diffuse linear PC staining for C4d, and histology consistent with Banff grade III in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis served as controls. First biopsies (post-transplantation day 16.2 ± 2.2): The intra-Capillary exudate comprised monocytes (59%), polymorphonuclears (14%), lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns of focal PC endothelial injury were observed: lysis, an increased rate of apoptosis and fragmentation. No correlation was found between the respective damage types and the inflammatory cell types or the Banff grades. Controls revealed endothelial swelling, detachment from basement membrane and fragmentation. Follow-up biopsies: Monocytes transformed into macrophages intra-luminally. The reparative changes comprised endothelial cytoplasmic protrusions, binucleated endothelial cells and Capillary sprouts. Early transplant capillaropathy and transplant glomerulopathy were noted in 2 recipients. Literature data indicate that lysis is mediated by anti-HLA alloantibodies; apoptosis, demonstrated first in the present study, may be induced by non-HLA-type anti-endothelial antibodies. Fragmentation is caused by ischemia. Ongoing endothelial injury leads to transplant capillaropathy and transplant glomerulopathy, the characteristic lesions of chronic rejection.
Edit Szederkenyi - One of the best experts on this subject based on the ideXlab platform.
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Peritubular Capillary basement membrane multilayering in early and advanced transplant glomerulopathy quantitative parameters and diagnostic aspects
Virchows Archiv, 2016Co-Authors: Dejan Dobi, E Kemeny, Edit Szederkenyi, Pal Szenohradszky, Zsolt Bodo, Laszlo Bidiga, Zoltan Hodi, Aniko Szilvasi, Bela IvanyiAbstract:The ultrastructural quantitative aspects of Peritubular Capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTCcirc). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3). Their respective clinical, serological, and morphological characteristics were then compared. The clinical data revealed that mild TG corresponded to early chronic antibody-mediated rejection (cABMR), while moderate-to-severe TG corresponded to the advanced stage of the disease. The permissive threshold displayed the lowest specificity (73 %) and the highest sensitivity (83 %) for moderate-to-severe TG, and its corresponding PTCcirc value was 3 layers. In contrast, the strict threshold—adopted by the Banff 2013 classification—displayed a specificity and sensitivity of 93 and 52 %, respectively, and the corresponding PTCcirc was 4 layers. In mild TG, 26 % of the cases met the permissive cutoff and 6 % the strict cutoff. Mild TG was associated with a lower PTCcirc (2.6 layers vs 4.5 layers in moderate-to-severe TG; p < 0.0001). Amongst the various criteria, the permissive criterion was associated most frequently with mild TG, and had prognostic relevance. Because of this, we propose its usage as a marker of early cABMR-induced PTCBML if non-alloimmune causes of PTCBML can be ruled out.
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Peritubular Capillary basement membrane changes in chronic renal allograft rejection comparison of light microscopic and ultrastructural observations
Virchows Archiv, 2011Co-Authors: Bela Ivanyi, E Kemeny, Zita Morvay, Pal Szenohradszky, Peter Rago, Norbert Lazar, Krisztina Boda, Edit SzederkenyiAbstract:Marked Peritubular Capillary basement membrane (PTCBM) multilayering, the ultrastructural feature of chronic antibody-mediated rejection (ABMR) of kidney allografts, was found to correspond histologically to PTCs with thickened BMs; such PTCs have been suggested as a novel histological marker of chronic rejection. We investigated whether scoring of PTCBM thickening can substitute the ultrastructural search for PTCBM multilayering. The thickening was graded in PAS- and Jones-stained sections in 110 biopsies from recipients with a late dysfunction, all examined ultrastructurally for transplant capillaropathy (≥3 PTCs with ≥5 BM layers). Grade 0 indicated no thickening. Grade 1 and grade 2 were assigned when the PTCBMs were as thick as or thicker than those of the non-atrophic tubules, and duplication/chain-like lamination of the PTCBM was noted in ≤3 or ≥4 high-power fields, respectively. The series was enrolled in subgroups of those with and those without histopathological lesions of chronic rejection. Fifty-six biopsies displayed lesions of chronic ABMR. Transplant capillaropathy was demonstrated in 40 biopsies. Grade 2 thickening furnished a substantial interobserver concordance rate (κ = 0.803) and correlated with the transplant capillaropathy. Jones staining performed somewhat better in scoring than PAS staining. Grade 2 thickening was verified in 35 biopsies involving chronic ABMR, and in one control biopsy (sensitivity 61.4%, specificity 0.98). Grade 1 thickening was not suggestive of chronic ABMR at all. In conclusion, grade 2 thickening can be regarded as the histopathological lesion of chronic ABMR; however, electron microscopy remains the gold standard in the assessment of PTCBM changes.
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Peritubular Capillary damage in acute humoral rejection an ultrastructural study on human renal allografts
American Journal of Transplantation, 2005Co-Authors: Peter Liptak, E Kemeny, Zita Morvay, Edit Szederkenyi, Pal Szenohradszky, F Marofka, J Toldi, M Exner, Bela IvanyiAbstract:The ultrastructural features of Peritubular Capillary (PC) damage was studied in 12 kidney allografts with acute humoral rejection (AHR). AHR manifested in diffuse linear PC staining for C4d, and histology consistent with Banff grade III in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis served as controls. First biopsies (post-transplantation day 16.2 ± 2.2): The intra-Capillary exudate comprised monocytes (59%), polymorphonuclears (14%), lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns of focal PC endothelial injury were observed: lysis, an increased rate of apoptosis and fragmentation. No correlation was found between the respective damage types and the inflammatory cell types or the Banff grades. Controls revealed endothelial swelling, detachment from basement membrane and fragmentation. Follow-up biopsies: Monocytes transformed into macrophages intra-luminally. The reparative changes comprised endothelial cytoplasmic protrusions, binucleated endothelial cells and Capillary sprouts. Early transplant capillaropathy and transplant glomerulopathy were noted in 2 recipients. Literature data indicate that lysis is mediated by anti-HLA alloantibodies; apoptosis, demonstrated first in the present study, may be induced by non-HLA-type anti-endothelial antibodies. Fragmentation is caused by ischemia. Ongoing endothelial injury leads to transplant capillaropathy and transplant glomerulopathy, the characteristic lesions of chronic rejection.
P F Halloran - One of the best experts on this subject based on the ideXlab platform.
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Peritubular Capillary changes and c4d deposits are associated with transplant glomerulopathy but not iga nephropathy
American Journal of Transplantation, 2004Co-Authors: Attapong Vongwiwatana, Sita Gourishankar, Patricia Campbell, Kim Solez, P F HalloranAbstract:We examined our renal transplant population for glomerular diseases demonstrated on biopsy between January 1993 and April 2002, focusing on transplant glomerulopathy (TGP). Of 1156 patients followed in our clinics during this period, glomerular disease was diagnosed in 132 cases (11.4%). Glomerulonephritis was diagnosed in 86 transplants (7.4%), with IgA nephropathy (IgAN) being the commonest diagnosis [32 cases (2.8%)]. Thirty-one cases (2.7%) of biopsy-proven TGP were analyzed for associated factors compared with 27 cases (2.3%) of recurrent IgAN. Transplant glomerulopathy was less frequent with mycophenolate mofetil (MMF) and/or tacrolimus, whereas recurrent IgAN showed no such tendency (P= 0.02). Peritubular Capillary (PTC) C4d deposition was observed in six of 24 cases (25%) with TGP but none with recurrent IgAN (P= 0.02). Peritubular Capillary basement membrane (BM) multilayering was significantly greater in TGP (4.92 ± 2.94) than in recurrent IgAN (1.86 ± 1.04) (P < 0.001). The graft survival of TGP was worse than recurrent IgAN (P= 0.05). The association of TGP with BM multilayering and C4d deposits in PTC suggests a generalized disorder of the graft microcirculation and its BM, owing to antibody-mediated rejection in at least some cases. Transplant glomerulopathy has a serious prognosis but is less frequent in patients on newer immunosuppression, unlike recurrent IgAN.
Yaser Hosny Ali Elewa - One of the best experts on this subject based on the ideXlab platform.
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induced expression of toll like receptor 9 in Peritubular Capillary endothelium correlates with the progression of tubulointerstitial lesions in autoimmune disease prone mice
Lupus, 2019Co-Authors: Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali ElewaAbstract:BACKGROUND: Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood-urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of Peritubular Capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice. METHODS: Lupus-prone BXSB/MpJ-Yaa (Yaa) and BXSB/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis. RESULTS: Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24 wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24 wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta ( Il1b), Il6, interferon gamma ( Ifng), and tumor necrosis factor alpha ( Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24 wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24 wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules ( P < 0.05 and 0.01). CONCLUSION: Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.
Alex B Magil - One of the best experts on this subject based on the ideXlab platform.
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focal Peritubular Capillary c4d deposition in acute rejection
Nephrology Dialysis Transplantation, 2006Co-Authors: Alex B Magil, Kathryn J TinckamAbstract:BACKGROUND: Diffuse Peritubular Capillary (PTC) C4d deposition has been shown to be associated with relatively poor graft outcome. The significance of focal PTC C4d staining in the early post-transplant period is uncertain. METHODS: Sixty-five biopsies from 53 patients with acute rejection were graded (Banff '97 criteria), stained for C4d, monocytes and T cells, and divided into three groups according to PTC C4d: (i) focal C4d (F) (14 biopsies, 14 patients), (ii) diffuse C4d (D) (23 biopsies, 15 patients) and (iii) no C4d (N) (28 biopsies, 24 patients). The three groups were compared with respect to a variety of biopsy and clinical parameters including outcome. RESULTS: The incidence of transplant glomerulitis and glomerular monocyte infiltration were significantly greater in F (64% and 2.0+/-2.0) and D (57% and 3.4+/-2.0) than in N (11% and 0.2+/-0.2). A significantly higher proportion of F (93%) demonstrated acute cellular rejection (Banff '97 grade > or = 1A) than did D (35%). The F and D groups included significantly more females (50 and 67%, respectively) than did N (21%). The percentage of patients with a second or third transplant was higher in F (29%) and D (40%) than in N (8%) (P = 0.0589). The proportion of patients with glomerular filtration rate F > N group) (P = 0.0416). CONCLUSION: The results suggest that the biopsy findings and clinical course in patients with focal PTC C4d staining are similar to those associated with diffuse C4d.
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infiltrating cell types in transplant glomerulitis relationship to Peritubular Capillary c4d deposition
American Journal of Kidney Diseases, 2005Co-Authors: Alex B MagilAbstract:BACKGROUND: Transplant glomerulitis may be part of the acute rejection process in some transplant recipients. Glomerular monocytes have been shown to be the predominant cell type in transplant glomerulitis associated with Peritubular Capillary C4d deposition. Whether this applies to Peritubular Capillary C4d-negative (C4d-) biopsy specimens with transplant glomerulitis is unknown. METHODS: Forty-two biopsy specimens with acute rejection and transplant glomerulitis were immunostained for monocytes, T cells, and C4d. In each biopsy specimen, glomerular monocytes and T cells were counted, and mean numbers of monocytes per glomerulus and T cells per glomerulus were determined. RESULTS: Peritubular Capillary C4d staining was present in 20 biopsy specimens (C4d-positive [C4d+] group) and negative in 22 specimens (C4d- group). There was no significant difference between mean Banff 97 glomerular scores for the 2 groups (C4d+ , 1.60 +/- 0.80; C4d- , 1.77 +/- 0.90). Although the C4d+ group showed a significantly higher mean number of monocytes per glomerulus (3.01 +/- 2.35) than the C4d- group (0.95 +/- 1.00; P < 0.0001), the C4d- group showed a significantly higher mean number of T cells per glomerulus (4.05 +/- 3.05) than the C4d+ group (1.36 +/- 1.24; P = 0.0007). There were proportionately more C4d+ biopsy specimens with a monocyte-T-cell ratio greater than 1.0 (75%) than C4d- specimens (14%; P < 0.0001). Mean glomerular monocyte-T-cell ratio was 3.66 +/- 4.24 for the C4d+ group and 0.39 +/- 0.54 for the C4d- group; the difference was significant (P = 0.0009). CONCLUSION: In acute rejection with no Peritubular Capillary C4d deposition, the predominant infiltrating endoCapillary cell in transplant glomerulitis is the T cell, unlike acute rejection with Peritubular Capillary C4d deposition, in which the predominant infiltrating glomerular cell is the monocyte.
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monocytes and Peritubular Capillary c4d deposition in acute renal allograft rejection1
Kidney International, 2003Co-Authors: Alex B Magil, Kathryn J TinckamAbstract:Monocytes and Peritubular Capillary C4d deposition in acute renal allograft rejection. Background Peritubular Capillary (PTC) deposition of complement split factor C4d in renal allografts has been shown to be closely associated with circulating antidonor antibodies and a marker for relatively poor graft survival. Monocyte/macrophage (MO) infiltration of renal allografts has been shown to adversely affect graft survival. The purpose of this study was to assess whether the two phenomena are related. Methods Twenty-three biopsies (from 15 patients) demonstrated diffuse strong staining of PTC for C4d (C4d+ group) and acute tubular injury with or without significant cellular rejection, while 28 biopsies (with acute rejection) but negative for PTC C4d served as controls (C4d- group). Results The C4d+ group demonstrated significantly greater glomerular and interstitial MO infiltration than did the C4d- group [3.4 ± 2.0 vs. 0.2 ± 0.3mO/glomerulus, P P = 0.0030]. Neutrophilic (PMN) infiltration of glomeruli and PTC was also significantly greater in the C4d+ group than in the C4d- one (0.8 ± 0.6 vs. 0.3 ± 0.3 PMN/glomerulus, P = 0.0003; 0.9 ± 0.8 vs. 0.4 ± 0.3 PTC PMN/hpf, P = 0.0035). Conclusion The results indicate a close association between PTC C4d deposition and MO infiltration, particularly glomerular, and confirm previous observations regarding the correlation of PTC C4d staining and PMN infiltration.