scholarly journals Capillary Dilation and Rarefaction Are Correlated with Intracapillary Inflammation in Antibody-Mediated Rejection

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xue Li ◽  
Qiquan Sun ◽  
Mingchao Zhang ◽  
Kenan Xie ◽  
Jinsong Chen ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Loss ◽  
Endothelial Damage ◽  
Cell Counting ◽  
Strongly Correlated ◽  
Peritubular Capillary ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
Capillary Dilation

Antibody-mediated rejection (ABMR) remains one of the major causes of graft loss after renal transplantation. It is dominated by endothelial damage in microcirculation. Clarifying the mechanism of microcirculating damage is obviously a key step to understand the pathogenesis of ABMR. Here we characterized capillary variation in ABMR and its possible mechanisms. Compared with T cell-mediated rejection and stable grafts, there was a significant dilation and rarefaction in peritubular capillaries (PTCs) of the ABMR group; Image-Pro Plus revealed a significantly larger intra-PTC area. Interestingly, the dilation of PTCs was strongly correlated with the intra-PTC cell counting. Moreover, peritubular capillary inflammation is correlated within situT-bet expression, and there was a good correlation between the intra-PTC expression of T-bet and the PTC diameter. HIF-1αup-regulation could be observed in ABMR but it was not necessary for capillary dilation. In general, ABMR is characterized with early capillary dilation and rarefaction; our data confirmed that the dilation is strongly correlated with intracapillary inflammation, which in turn is correlated within situT-bet expression. T-bet plays an important role in the development of microcirculating injury, and thus it is a potential target for the treatment of ABMR.

scholarly journals SO031ANGIOTENSIN II TYPE 1 RECEPTOR (AT1R) EXPRESSION IN RENAL TRANSPLANT BIOPSIES AND ANTI-AT1R ANTIBODIES IN SERUM AS AN INDICATOR OF THE RISK OF TRANSPLANT LOSS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Agnieszka Sas-Strózik ◽  
Piotr Donizy ◽  
Katarzyna Kościelska-Kasprzak ◽  
Dorota Kamińska ◽  
Kamila Gawlik ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Loss ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Positive Staining ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
One Year ◽  
Transplant Biopsy

Abstract Background and Aims The manifestation of anti-angiotensin II type 1 receptor (AT1R) antibodies is considered a risk factor for transplant injury, however, the occurrence of AT1-Receptor expression in renal transplant biopsy may be an additional feature which can help to predict transplant loss. The aim of our study was to evaluate the expression of AT1R together with their antibodies and assess the risk of transplant loss in patients who had a renal transplant indication biopsy. Method AT1-Receptor immunoreactivity was analyzed in renal transplant biopsies. Additionally, we analyzed the presence of anti-AT1R antibodies in these patients using ELISA method. The result of more than 10 was assessed as positive. Immunohistochemical evaluation of AT1-Receptor expression was performed on 4 μm-thick paraffin sections mounted on silanized slides. AT1-Receptor expression was analyzed in five compartments: 1.tubular epithelium, 2.glomeruli, 3.peritubular capillaries, 4.interstitium and 5.renal blood vessels (small and intermediate arteries) based on a 3-step scale. Results We checked 156 samples of biopsies for the immunoreactivity of the AT1-Receptor. In all these patients we were able to access the presence of anti-AT1R antibodies. A group of 67 patients had positive AT1-Receptor expression (R+) and 16 patients had positive anti-AT1R antibodies (R+Ab+) results. A group of 89 patients had no expression of AT1-Receptor (R-), among which 51 had also no anti-AT1R (R-Ab-). One-year post-biopsy graft loss in the R+Ab+ patients was 37% (6/16) compared to 10% (7/69) in the R-Ab- patients (p = 0.006). Two-year and three-year graft loss was 43% vs. 17% (p=0.02) and 50% vs. 21% (p=0.02) respectively. Moreover, six patients had positive staining of AT1-Receptors in microcirculation (glomeruli and peritubular capillaries), which was associated with antibody mediated rejection. Conclusion The presence of anti-AT1R antibodies in serum together with the expression of AT1-Receptor in transplant biopsy was associated with a significantly higher graft loss. The relevance of AT1-Receptor expression analyzed together with anti-AT1R antibodies should be considered for better transplant immunological risk assessment.

Renal transplantation

2020 ◽  
pp. 4879-4908
Author(s):  
Nicholas Torpey ◽  
John D. Firth
Keyword(s):  
Renal Transplantation ◽  
Supply And Demand ◽  
Transplant Rejection ◽  
Immunosuppressive Agents ◽  
Graft Loss ◽  
Parasitic Infections ◽  
First Year ◽  
Antibody Mediated Rejection ◽  
Standard Triple Therapy

Renal transplantation is the preferred option for the treatment of endstage chronic renal failure in patients for whom there are no major medical contraindications. In well-selected recipients, both life expectancy and quality of life are superior to treatment with long-term dialysis. However, as the dialysis population continues to grow, the gap between supply and demand for renal transplantation is widening. Immunosuppression—excepting for transplants between HLA-identical twins, immunosuppression is required to prevent rejection, but there is no clear consensus on the best immunosuppressive regimen. Most centres use an induction antibody directed against CD25 or a T-lymphocyte-depleting antibody (thymoglobulin or alemtuzumab), followed by what is now called standard triple therapy—comprising a calcineurin inhibitor (almost always tacrolimus), combined with either mycophenolate mofetil or azathioprine, and steroids. Steroids are not infrequently tailed off rapidly in the early post-transplant period. Transplant rejection can be classified into four main categories: (1) hyperacute, (2) accelerated, (3) acute cellular, and (4) humoral. Complications of renal transplantation—this chapter discusses specific and nonspecific side effects of immunosuppressive agents, infective complications (including viral, bacterial, fungal, and parasitic infections), malignant complications, and other complications (including hypertension, accelerated atherosclerosis, and electrolyte, musculoskeletal, haematological, gastrointestinal, and cosmetic disorders) in detail. Prognosis—first-year transplant losses from rejection have been dramatically reduced from about 40% in the 1970s to 5%. However, the rate of chronic graft loss remains at about 4% per year. The commonest cause of insidious late graft failure is probably chronic antibody-mediated rejection, frequently associated with poor adherence to immunosuppression. Calcineurin toxicity may also contribute. A major focus of research is to identify non-nephrotoxic immunosuppressive agents able to suppress antibody-mediated rejection.

scholarly journals Peri-operative third party red blood cell transfusion in renal transplantation and the risk of antibody-mediated rejection and graft loss

2013 ◽  
Vol 29 (1-4) ◽  
pp. 22-27 ◽  
Author(s):  
Samantha Fidler ◽  
Ramyasuda Swaminathan ◽  
Wai Lim ◽  
Paolo Ferrari ◽  
Campbell Witt ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Graft Loss ◽  
Third Party ◽  
Red Blood Cell Transfusion ◽  
Antibody Mediated Rejection

scholarly journals The Diagnostic Value of Transcription Factors T-bet/GATA3 Ratio in Predicting Antibody-Mediated Rejection

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Xue Li ◽  
Qiquan Sun ◽  
Mingchao Zhang ◽  
Jinsong Chen ◽  
Zhihong Liu
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
Acute Rejection ◽  
Diagnostic Value ◽  
Steroid Treatment ◽  
Strongly Correlated ◽  
Peritubular Capillary ◽  
Antibody Mediated Rejection

Background. Previous data showed that the predominance of intraglomerular T-bet or GATA3 is correlated with different mechanisms of rejection, suggesting that the ratio of T-bet/GATA3 might be used to distinguish antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR).Methods. We compared the intraglomerular T-bet/GATA3 ratio in ABMR and TCMR. The intragraft expression of T-bet and GATA3 was studied via immunohistochemistry. The correlation of the diagnosis of AMR with the ratio of T-bet/GATA3 was examined.Results. Both intraglomerular T-bet- and GATA3-expressing cells were increased during acute rejection. T-bet/GATA3>1 was strongly correlated with ABMR (93.3% versus 18.2%). The incidence of positive HLA-I/II antibodies and glomerulitis is significantly higher in T-bet/GATA3>1 group (P<0.001,0.013, resp.). The scores of peritubular capillary inflammation and glomerulitis were also higher in T-bet/GATA3>1 group (P=0.052,P<0.001, resp.). Nevertheless, T-bet/GATA3>1 is also correlated with C4d-negative ABMR and resistance to steroid treatment. Compared with C4d deposition, T-bet/GATA3>1 had a slight lower (90% versus 100%) specificity but a much higher (87.5% versus 68.8%) sensitivity.Conclusion. Our data suggested that intraglomerular predominance of T-bet over GATA3 might be used as diagnosis maker of ABMR in addition to C4d, especially in C4d-negative cases.

72-P Pre-transplant HLA-DSA that persist post-transplant predict increased risk of antibody-mediated rejection and graft loss in renal transplantation

2011 ◽  
Vol 72 ◽  
pp. S66
Author(s):  
Patrizia Amico ◽  
Nubia Banuelos ◽  
Gideon Hönger ◽  
Helmut Hopfer ◽  
Stefan Schaub ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Loss ◽  
Post Transplant ◽  
Antibody Mediated Rejection ◽  
Increased Risk

scholarly journals The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage -

2019 ◽  
Vol 20 (18) ◽  
pp. 4544 ◽  
Author(s):  
Tsukasa Nakamura ◽  
Takayuki Shirouzu ◽  
Katsuya Nakata ◽  
Norio Yoshimura ◽  
Hidetaka Ushigome
Keyword(s):  
Major Histocompatibility Complex ◽  
Organ Transplantation ◽  
Current Knowledge ◽  
Human Leukocyte ◽  
Strongly Correlated ◽  
Human Beings ◽  
Major Histocompatibility ◽  
Antibody Mediated Rejection ◽  
Leukocyte Antigens ◽  
Histocompatibility Complex

Organ transplantation has progressed with the comprehension of the major histocompatibility complex (MHC). It is true that the outcome of organ transplantation largely relies on how well rejection is managed. It is no exaggeration to say that to be well acquainted with MHC is a shortcut to control rejection. In human beings, MHC is generally recognized as human leukocyte antigens (HLA). Under the current circumstances, the number of alleles is still increasing, but the function is not completely understood. Their roles in organ transplantation are of vital importance, because mismatches of HLA alleles possibly evoke both cellular and antibody-mediated rejection. Even though the control of cellular rejection has improved by recent advances of immunosuppressants, there is no doubt that antibody-mediated rejection (AMR), which is strongly correlated with donor-specific anti-HLA antibodies (DSA), brings a poor outcome. Thus, to diagnose and treat AMR correctly is a clear proposition. In this review, we would like to focus on the detection of intra-graft DSA as a recent trend. Overall, here we will review the current knowledge regarding MHC, especially with intra-graft DSA, and future perspectives: HLA epitope matching; eplet risk stratification; predicted indirectly recognizable HLA epitopes etc. in the context of organ transplantation.

scholarly journals Preceding T-Cell-Mediated Rejection Is Associated with the Development of Chronic Active Antibody-Mediated Rejection by de Novo Donor-Specific Antibody

Nephron ◽  
2020 ◽  
pp. 1-5
Author(s):  
Takahiro Tsuji ◽  
Sari Iwasaki ◽  
Keishi Makita ◽  
Teppei Imamoto ◽  
Naomichi Ishidate ◽  
...  
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
De Novo ◽  
Control Group ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
The Mean ◽  
Microvascular Inflammation ◽  
Renal Allograft Loss ◽  
Allograft Loss

<b><i>Aim:</i></b> Chronic active antibody-mediated rejection (CAABMR) is an important cause of late-stage renal allograft loss. Early inflammatory events such as acute rejection and infection after transplantation are considered to be the risk factors of de novo donor-specific antibody (dnDSA) production. In this study, we investigated the relationship between pre­disposing T-cell-mediated rejection and dnDSA-positive CAABMR. <b><i>Methods:</i></b> We recruited 365 patients who underwent ABO-compatible renal transplantation at our hospital. Among them, 16 patients diagnosed as having dnDSA-positive CAABMR were designated as a CAABMR group, and 38 randomly selected patients were designated as a control group. All biopsies from 1 month after transplantation were included in the study. The presence or absence of borderline changes (BLCs), acute T-cell-mediated rejection (ATMR), microvascular inflammation (MVI), and C4d positive on peritubular capillaries (C4d-P) was examined. <b><i>Results:</i></b> In the CAABMR group, BLC/ATMR was found in 12 cases (75%), and the mean duration until appearance of BLC/ATMR was 282.7 ± 328.7 days. C4d-P was found in 11 cases (68.8%), and the mean duration until its appearance was 1,432 ± 1,307 days. MVI was found in all cases, and the mean duration until its appearance was 1,333 ± 1,126 days. The mean duration until diagnosis of CAABMR was 2,268 ± 1,191 days. In the control group, BLC/ATMR was found in 13 cases (34.2%), and the mean duration until the appearance of BLC/ATMR was 173.1 ± 170.4 days. C4d-P was found in 2 cases (5.3%), and the durations until its appearance were 748 and 1,881 days. No cases of MVI were found in the control group. The frequency of BLC/ATMR was significantly higher in the CAABMR group (<i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> Preceding BLC/ATMR is associated with the development of CAABMR with dnDSA.

Outcomes of Combination Therapy for Chronic Antibody-Mediated Rejection in Renal Transplantation

2012 ◽  
Vol 94 (10S) ◽  
pp. 1049
Author(s):  
M.-G. Kim ◽  
H. Y. Kwon ◽  
T. Y. Koo ◽  
Y. J. Kim ◽  
J. H. Park ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Combination Therapy ◽  
Antibody Mediated Rejection

Postoperative production of anti-donor antibody and early graft loss due to vascular rejection in renal transplantation

1998 ◽  
Vol 30 (7) ◽  
pp. 2963 ◽  
Author(s):  
M Abe ◽  
A Sannomiya ◽  
T Koike ◽  
S Sato ◽  
J Sageshima ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Loss ◽  
Vascular Rejection ◽  
Early Graft
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