Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection (original) (raw)
Related papers
Clinical Nephrology, 2011
The use of C4d staining as a tissue marker for humoral immunity has served an important role in allowing pathologists to more accurately diagnose acute antibody-mediated rejection (AMR) in renal and other allograft biopsies, and also to recognize the contribution of humoral immunity to lesions of chronic renal allograft rejection, including transplant glomerulopathy. However, while C4d remains a specifi c marker of a humoral response, recent evidence indicates that a considerable fraction of renal allograft biopsies showing antibody-mediated injury are C4d-negative, even by immunofl uorescence. This review summarizes the current evidence supporting the existence of C4d-negative AMR, as well as evidence that this entity may, if untreated, lead to the development of scarring within the graft, transplant glomerulopathy and even graft loss.
Diagnosis and treatment of antibody-mediated kidney allograft rejection
Transplant International, 2003
Evidence of a significant pathogenetic role of donor-reactive antibodies (DRA) in kidney allograft rejection is accumulating. At least, partially owing to the recent discovery of the complement split product C4d as a valuable rejection marker, antibody-mediated rejection (AMR) has regained increasing attention. We review here the value of various diagnostic criteria, including immunohistochemistry (C4d staining), histomorphology and posttransplant serology, for the diagnosis of AMR. Furthermore, the mechanisms underlying alloantibody/complement-mediated allograft injury are discussed in detail. Finally, a thorough discussion of recently proposed "anti-humoral" therapeutic strategies is provided. Keywords Antibody-mediated rejection. Apheresis. C4d. Immunoadsorption. Kidney. Transplantation Abbreviations AHR Acute humoral rejection. A M R Antibody-mediated rejection. DARC Duffy antigen/ receptor for chemokines. DRA Donor-reactive antibodies. FCXM Posttransplant flow cytometry. ZA Immunoadsorption. Z g Immunoglobulin. iTCC Inactive terminal complement complex. ZVZG Intravenous immunoglobulin. rnAb Monoclonal antibodies. MAC Membrane attack complex. PTC Peritubular capillaries. PP Plasmapheresis. v W F von Willebrand factor .
Pathology of C4d-negative antibody-mediated rejection in renal allografts
Current opinion in organ transplantation, 2013
To summarize current evidence supporting the existence of C4d-negative antibody-mediated rejection (AMR) in renal allografts, its potential to cause chronic graft injury, and whether histopathologic features of C4d-negative AMR differ from those of C4d-positive AMR. Recently published molecular, clinicopathologic, and ultrastructural studies provide strong evidence that microvascular injury in the presence of donor-specific alloantibodies (DSA) has the potential to cause interstitial fibrosis/tubular atrophy, transplant glomerulopathy, and graft loss, whether or not peritubular capillary (PTC) C4d is present. Although C4d-positive AMR may represent a more severe form of AMR, recent studies have found that in patients with DSA, microvascular injury (glomerulitis, peritubular capillaritis) is more strongly associated with graft loss than C4d deposition. Our data suggest that C4d-positive and C4d-negative AMR show similar degrees of glomerulitis and peritubular capillaritis, similar fr...
We examined rejection outcome and graft survival in 58 adult patients with acute cellular rejection Banff type I (ARI) or II (ARII), within 1 year after trans-plantation, with or without CD20-positive infiltrates. Antibody-mediated rejection was not examined. Of the 74 allograft biopsies, performed from 1999 to 2001, 40 biopsies showed ARI and 34 biopsies showed ARII; 30% of all the biopsies showed CD20-positive clusters with more than 100 cells, 9% with more than 200 cells and 5% with more than 275 cells. Patients with B cell-rich (>100 or >200/HPF CD20-positive cells) and B cell-poor biopsies (<50 CD20-positive cells/HPF) were compared. Serum creatinine and eGFR of B cell-rich (CD20 > 100/HPF) and B cell-poor were not significantly different at rejection, or at 1, 3, 6 and 12 months, and during additional 3 years follow-up after rejection, although higher creatinine at 1 year was noted in the >200/HPF group. Graft survival was also not different between B cell-rich and B cell-poor groups (p = 0.8 for >100/HPF, p = 0.9 for >200/HPF CD20-positive cells). Our data do not support association of B cell-rich infiltrates in allograft biopsies and worse outcome in acute rejection type I or II, but do not exclude the possible contribution of B cells to allograft rejection.
Antibody-Mediated Renal Allograft Rejection: Diagnosis and Pathogenesis
Journal of the American Society of Nephrology, 2007
Alloantibodies to HLA class I or II and other antigens expressed by endothelium cause a variety of effects on renal transplants, ranging from acute to chronic rejection, and even apparent graft acceptance (accommodation). Recognition of these conditions and appropriate therapy requires demonstration of C4d in biopsies, commonly confirmed by tests for circulating alloantibody. Substantial practical experience by pathologists in the interpretation and pitfalls of C4d stains are reviewed along with considerations of the clinical significance and pathologic mechanisms of the different effects of antibody on the endothelium of the renal allograft. Clinical trials will be needed to ascertain the optimal treatment for the newly appreciated conditions chronic humoral rejection and accommodation.
Journal of clinical and diagnostic research : JCDR, 2016
Biopsy remains gold standard for diagnosis of Graft Dysfunction (GD). It guides clinical management, provides valuable insights into pathogenesis of early and late allograft injury and is indispensable for distinguishing rejection from non- rejection causes of GD. The primary aim of the study was to evaluate the diverse histomorphological lesions in renal allograft biopsy (RAB). Further, we determined the frequency of peritubular capillary (PTC) C4d positivity and its correlation with microvascular inflammation in Antibody Mediated Rejection (AMR). This was a prospective study on RAB over a period of 2 months. Histopathological evaluation was undertaken as per revised Banff'13 schema. Immunohistochemistry was performed to detect PTC C4d deposition. Sixty five diagnostic biopsies were evaluated. Mean patient age was 34 years and males were predominant. The time interval between graft biopsy and transplantation ranged from 5 days to 8 years, with 52.3% biopsies belonging to period...
An updated Banff schema for diagnosis of antibody-mediated rejection in renal allografts
Current opinion in organ transplantation, 2014
To introduce the updated Banff schema for antibody-mediated renal allograft rejection and related revisions to definitions within this schema agreed upon during and immediately subsequent to the 2013 Banff Conference on Allograft Pathology. The original Banff schema for diagnosis of acute and chronic, active antibody-mediated rejection (ABMR) in renal allografts, formulated at the 2001 and 2007 Banff Conferences, has been of great assistance to pathologists and clinicians faced with an increasing awareness of the role of donor-specific alloantibodies (DSAs) in producing graft injury. This schema requires histologic (primarily microvascular inflammation and transplant glomerulopathy), immunohistologic (C4d in peritubular capillaries), and serologic (circulating DSA) evidence for a definitive diagnosis of ABMR. Still, like other Banff classifications, the 2001/2007 schema for renal ABMR is a working classification subject to revision based on new data. Increasing evidence for C4d-nega...
Antibody-Mediated Rejection in Renal Allografts
Clinical Journal of the American Society of Nephrology, 2006
The past 15 years have seen major advances in the understanding of the effects of anti-donor antibodies on renal allografts at various stages after transplantation. These advances have been due in large part to pathologic examination of both early and late renal allograft biopsies, including both routine histologic evaluation and immunohistology to detect complement split products. As pathologists have become increasingly adept at diagnosing antibody-mediated rejection (AMR) on allograft biopsies, substantial progress has been made in the treatment of AMR and in successful renal transplantation in recipients with pre-existing antibodies against donor blood group (ABO) and/or major histocompatibility (HLA) antigens. This article reviews the pathologic features of hyperacute, acute, and chronic AMR, including some newer findings impacting diagnosis and outcomes, and differences in the implications of similar pathologic findings in ABO-versus HLA-incompatible renal allografts.
2021
Associate professor, Dep’t of Pathology, MS Ramaiah Medical College And Hospitals, MSRIT Post, MSR Nagar, Bangalore560054. Associate professor, Department of Nephrology, MS Ramaiah Medical College And Hospitals, MSRIT Post, MSR Nagar, Bangalore560054. Tutor, Dep’t of Pathology, MS Ramaiah Medical College And Hospitals., MSRIT Post, MSR Nagar, Bangalore560054. Professor and HoD, Department of Nephrology. MS Ramaiah medical college and hospitals, MSRIT Post, MSR Nagar, Bangalore560054 Senior professor, Dep’t of Pathology, MS Ramaiah medical college and hospitals, MSRIT Post, MSR Nagar, Bangalore560054. ARTICLE INFO ABSTRACT