- Due to circulating antibodies against donor HLA, non-HLA or ABO antigens, i.e. donor specific antibodies (DSA) ( Clin Biochem 2016;49:320 )
- DSAs can be preformed (in which case antibody mediated rejection occurs during the very early posttransplant period - hyperacute / accelerated rejection) or may develop de novo after transplantation (usually due to inadequate immunosuppression or nonadherence)
What is positive antibody mediated rejection pamr-2?
pAMR1 (I+) - Positive immunohistochemical or immunofluorescence staining according to criteria outlined further into the tutorial, with normal biopsy histology. pAMR2 - Characterized by both histopathological changes and immunopathological findings (i.e. pAMR (H+) + pAMR (I+) = pAMR2). pAMR3 - Severe antibody mediated rejection.
What is the difference between an antibody and antibiotic?
is that antibodyis (immunology) a protein produced by b-lymphocytes that binds to a specific antigen while antibioticis (pharmacology) any substance that can destroy or inhibit the growth of bacteria and similar microorganisms. As an adjective antibioticis (pharmacology) of or relating to antibiotics. antibody English (wikipedia antibody) Noun
What is the treatment for kidney rejection?
Renal Transplant Rejection. When your kidneys fail to function totally and it is irreversible, dialysis and kidney transplantation are the two treatment options available for your condition. If you are a suitable candidate for a kidney transplant and a compatible donor is found for you, the operation is performed.
What does a positive GAD antibody panel mean?
What does positive GAD antibodies mean? The presence of GAD autoantibodies indicates an immune system attack, which points to type 1 diabetes. Type 1 diabetes isn’t the only reason someone might have GAD autoantibodies. These antibodies are also linked to other conditions, which include: Cerebellar ataxia. ...
How does antibody mediated rejection occur?
AMR results from activation of the classical pathway of the complement system by antibodies against the donor HLA present on the endothelium. These antibodies may be preformed prior to transplantation or can arise de novo after transplantation.
What does antibody mediated rejection mean?
Antibody-mediated rejection (AMR) defines all allograft rejection caused by antibodies directed against donor-specific HLA molecules, blood group antigen (ABO)-isoagglutinins, or endothelial cell antigens.
How common is antibody mediated rejection?
Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence.
Why do transplant rejections occur?
This is because the person's immune system detects that the antigens on the cells of the organ are different or not "matched." Mismatched organs, or organs that are not matched closely enough, can trigger a blood transfusion reaction or transplant rejection.
Is antibody mediated rejection treatable?
Clinical manifestations of AMR include proteinuria and a rise in serum creatinine. Current strategies for the treatment of AMR include antibody depletion with plasmapheresis (PLEX), immunoadsorption (IA), immunomodulation with intravenous immunoglobulin (IVIG), and T cell– or B cell–depleting agents.
Is organ rejection an autoimmune disorder?
Col(V) is highly conserved; therefore, these data indicate that transplant rejection involves both alloimmune and autoimmune responses.
Which organ has highest risk of rejection?
In heart transplants, the rate of organ rejection and patient mortality are the highest, even though the transplants are monitored by regular biopsies. Specifically, some 40% of heart recipients experience some type of severe rejection within one year of their transplant.
Can stress cause transplant rejection?
However, we have now seen 11 patients in whom an acute rejection occurred just after emotional stress. There appears to be a clear relationship between psychological stress and rejection.
What transplant has lowest risk for rejection?
Isograft: This type of transplant is done between a genetically identical donor and a recipient, such as an identical twin. There is virtually no risk of rejection in this case, as the body does not recognize an identical twin's organ as foreign.
Can you stop organ rejection?
Medications and Infections: Immunosuppressive Drugs After you have an organ transplant, you will need to take medication (immunosuppressants) for the rest of your life to keep your body from rejecting your new organ.
Which cell type is most responsible for transplant rejection?
The immune response to a transplanted organ consists of both cellular (lymphocyte mediated) and humoral (antibody mediated) mechanisms. Although other cell types are also involved, the T cells are central in the rejection of grafts.
What are the 3 types of organ rejection?
There are three major types of allograft rejection: Hyperacute, acute, and chronic rejection.
What does antibody-mediated mean?
Antibody-mediated immunity involves the activation of B cells and secretion of antibodies when in contact with a pathogen. When exposed to the chemicals released by activated helper T cells, a sensitized B cell divides, producing daughter cells that differentiate into memory B cells and plasma cells.
What is the difference between acute cellular rejection and antibody-mediated rejection?
In contrast, antibody-mediated (or humoral) rejection (AMR) occurs owing to binding of preformed or de novo recipient antibodies directed against antigens that are expressed on the donor organ cells. Acute cell-mediated rejection (ACR) and AMR can occur within days, months, or even years after transplant.
What is antibody-mediated disease?
Antibody-mediated neuroinflammatory disorders are conditions where the body's immune system attacks its own cells in the central nervous system (the brain, spinal cord, and/or optic nerves).
What are antibody-mediated reactions?
Type II hypersensitivity reaction refers to an antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens, resulting in cellular destruction, functional loss, or damage to tissues. Damage can occur through multiple mechanisms.
What is the most common histologic finding associated with AMR?
68 The most common histologic finding described in association with AMR is capillary inflammation , which encompasses neutrophilic capillaritis and neutrophilic margination. 10,69,70 Neutrophilic capillaritis is defined as alveolar septal infiltrates composed of neutrophils and the presence of neutrophilic karyorrhectic debris and fibrinous exudates. 68 Fibrin thrombi in capillaries may or may not be observed. Neutrophilic margination is defined as a collection of neutrophils within the interstitial capillaries. 68 Karyorrhectic debris and fibrinous exudates are not seen. In addition to neutrophilic capillaritis and margination, acute lung injury/diffuse alveolar damage and endothelialitis also show correlation with circulating DSAs. 69 Other reported histologic findings include high-grade acute cellular rejection (grade A3 or A4), persistent and recurrent acute cellular rejection (any A grade), high-grade lymphocytic bronchiolitis (grade B2R), persistent low-grade lymphocytic bronchiolitis (grade B1R), and obliterative bronchiolitis (grade C1). 68 Unfortunately, none of the histologic findings are sufficiently sensitive or specific for AMR. 67
What is AMR in lung transplant?
AMR is related to antibodies present in lung all ografts. According to a consensus document issued by the ISHLT, measurable allograft dysfunction, the presence of circulating donor-specific antibodies, and positive C4d peritubular capillary staining should be considered diagnostic of AMR ( Levine et al., 2016) Table 8 lists the criteria for AMR in lung transplant recipients according to the ISHLT definition ( Levine et al., 2016 ).
What is hyperacute AMR?
Hyperacute AMR is due to preformed DSAs and occurs within seconds to minutes after vascular anastomoses: it leads to hemorrhagic necrosis and graft thrombosis.
What is clinical presentation of AMR?
Clinical Presentation. AMR can be clinical with measurable allograft dysfunction, such as hypoxemia and decreased FEV 1, or subclinical, with normal allograft function. 65,66 Patients with clinical AMR may have symptoms such as dyspnea, cough, fever, and malaise, or they may be asymptomatic.
What causes AMR?
AMR is caused by donor-specific antihuman leukocyte antigen antibodies (DSAs). These antibodies, which may develop before or after transplantation, bind to target antigens and activate the complement system. 61,62 Early observations of AMR were based on hyperacute rejection, in which preexistent antibodies lead to complement activation and rapid graft loss. With improved cross-matching before transplantation, the incidence of hyperacute rejection has decreased. On the other hand, improvements in DSA detection have increased the recognition of AMR after the immediate posttransplant period. 61,63,64
Where is C4D found?
C4d is often detected in peritubular capillaries and arterioles, regarded as evidence of a preexisting antibody event (immunoglobulins are not detected), and neutrophils or mononuclear inflammatory cells are usually present within glomerular tufts and dilated peritubular capillaries ( Fig. 1.156A-D ).
What are the criteria for AMR?
The diagnosis of pulmonary AMR remains a challenge and requires the correlation of clinical , radiologic , pathologic , serologic, and microbiologic findings. 67 Key diagnostic criteria include lung biopsy findings consistent with AMR, positive immunohistochemical staining for complement 4d (C4d), and detection of circulating DSAs. 65 A diagnosis of definite AMR can be made, if all three criteria are met. Two of the three criteria are required for a probable and one of the three criteria is required for a possible AMR diagnosis. Allograft dysfunction may bring the attention to AMR but is not required for the diagnosis (clinical vs. subclinical AMR). When there is measurable pulmonary allograft dysfunction, other potential causes of the dysfunction such as infection need to be excluded.
What is the most common histologic finding associated with AMR?
68 The most common histologic finding described in association with AMR is capillary inflammation , which encompasses neutrophilic capillaritis and neutrophilic margination. 10,69,70 Neutrophilic capillaritis is defined as alveolar septal infiltrates composed of neutrophils and the presence of neutrophilic karyorrhectic debris and fibrinous exudates. 68 Fibrin thrombi in capillaries may or may not be observed. Neutrophilic margination is defined as a collection of neutrophils within the interstitial capillaries. 68 Karyorrhectic debris and fibrinous exudates are not seen. In addition to neutrophilic capillaritis and margination, acute lung injury/diffuse alveolar damage and endothelialitis also show correlation with circulating DSAs. 69 Other reported histologic findings include high-grade acute cellular rejection (grade A3 or A4), persistent and recurrent acute cellular rejection (any A grade), high-grade lymphocytic bronchiolitis (grade B2R), persistent low-grade lymphocytic bronchiolitis (grade B1R), and obliterative bronchiolitis (grade C1). 68 Unfortunately, none of the histologic findings are sufficiently sensitive or specific for AMR. 67
How many patients have AMR after heart transplant?
AMR has been reported in up to 20% of patients early after HT and is also a significant component of late rejection with one study in adults and children reporting 25% of cases occurring greater than 1 year after HT [35,36]. Small single center studies have demonstrated pathologic AMR in 35%–59% of pediatric heart transplant patients [37,38]. The diagnosis of AMR has transitioned from one with both pathologic and clinical criteria to a pathologic diagnosis with guidelines for the pathologic criteria outlined by ISHLT [39]. Identified risk factors for AMR include female recipient, multiparity, blood product transfusions, positive perioperative T-cell flow cytometry crossmatch, pretransplant allosensitization, MCS, and previous surgery for congenital heart disease, especially involving homograft tissue [35,40,41]. Pediatric studies have demonstrated an association between AMR, CAV, and graft failure; however, there has been no large scale analysis of the impact of patient survival following the diagnosis of AMR nor comparison to those with ACR [37,40,42]. Current therapies to treat AMR are targeted toward the removal and blockade of circulating antibodies, B-lymphocyte and plasma cell depletion, suppression of T-lymphocyte-dependent antibody responses, and inhibition of the complement cascade. These will be discussed in further detail later in this chapter.
What is AMR in medical terms?
Acute antibody-mediated rejection (AMR) or acute humoral rejection occurs in patients who are presensitized or who develop a threshold level of de novo donor specific antibody (DSA) at any point after transplantation. There are no specific clinical features that distinguish acute T-cell-mediated rejection (TCMR) from acute AMR. The histologic findings in acute AMR are often characteristic but quite variable and may resemble acute tubular injury or thrombotic microangiopathy (TMA) and may be obscured by features of TCMR. Thus, establishing the diagnosis of acute AMR entails careful correlation between clinical, histologic, and other laboratory findings. This chapter is excerpted and updated from a previous review. 1
What are the criteria for pulmonary AMR?
The diagnosis of pulmonary AMR remains a challenge and requires the correlation of clinical, radiologic, pathologic, serologic, and microbiologic findings. 67 Key diagnostic criteria include lung biopsy findings consistent with AMR, positive immunohistochemical staining for complement 4d (C4d), and detection of circulating DSAs. 65 A diagnosis of definite AMR can be made, if all three criteria are met. Two of the three criteria are required for a probable and one of the three criteria is required for a possible AMR diagnosis. Allograft dysfunction may bring the attention to AMR but is not required for the diagnosis (clinical vs. subclinical AMR). When there is measurable pulmonary allograft dysfunction, other potential causes of the dysfunction such as infection need to be excluded.
What are the criteria for AMR?
The diagnosis of pulmonary AMR remains a challenge and requires the correlation of clinical , radiologic , pathologic , serologic, and microbiologic findings. 67 Key diagnostic criteria include lung biopsy findings consistent with AMR, positive immunohistochemical staining for complement 4d (C4d), and detection of circulating DSAs. 65 A diagnosis of definite AMR can be made, if all three criteria are met. Two of the three criteria are required for a probable and one of the three criteria is required for a possible AMR diagnosis. Allograft dysfunction may bring the attention to AMR but is not required for the diagnosis (clinical vs. subclinical AMR). When there is measurable pulmonary allograft dysfunction, other potential causes of the dysfunction such as infection need to be excluded.
What is the treatment for AMR?
The treatment of AMR involves the same interventions that are used to treat AMR in heart transplantation, which include depletion of circulating antibodies, suppression of B-cells and prevention of antibody-mediated allograft injury.
What causes AMR?
AMR is caused by donor-specific antihuman leukocyte antigen antibodies (DSAs). These antibodies, which may develop before or after transplantation, bind to target antigens and activate the complement system. 61,62 Early observations of AMR were based on hyperacute rejection, in which preexistent antibodies lead to complement activation and rapid graft loss. With improved cross-matching before transplantation, the incidence of hyperacute rejection has decreased. On the other hand, improvements in DSA detection have increased the recognition of AMR after the immediate posttransplant period. 61,63,64
What is the Banff 1997 classification?
The 1997 Banff classification was used to classify rejection prior to the meeting in 2001, which further defined pathological classification of AMR [ 12#N#L. C. Racusen, R. B. Colvin, K. Solez et al., “Antibody-mediated rejection criteria—an addition to the Banff '97 classification of renal allograft rejection,” American Journal of Transplantation, vol. 3, no. 6, pp. 708–714, 2003. View at: Publisher Site | Google Scholar#N#See in References#N#]. Gorer determined the role of antibody after much debate in the early days of transplantation, and unfortunately after his death in 1961 the concept of AMR was lost. In 1991-1992, Feucht and Halloran described C4d as a marker for AMR however this was not uniformly utilized until the report from Solez et al. in 1998–2000 [ 13#N#K. Solez, R. B. Colvin, L. C. Racusen et al., “Banff 07 classification of renal allograft pathology: updates and future directions,” American Journal of Transplantation, vol. 8, no. 4, pp. 753–760, 2008. View at: Publisher Site | Google Scholar#N#See in References#N#]. After international transplant meetings in 1997, AMR was an entity recognized by most of the participants and C4d staining raised hope that morphological classification of AMR can be further defined. Incidence of AMR has been reported as 0–8% in renal transplant recipients in larger centers largely due to increased recognition, detection of DSA, retransplanted patients, as well as increase in positive crossmatch and ABO incompatible transplantation for highly sensitized patients. Colvin had reviewed studies from Massachusetts General Hospital which for the first time indicated a clear correlation of peritubular capillary C4d staining pathological features with DSA in AMR. A few studies have indicated C4d staining is around 93–96% specific, but 31–95% sensitive [ 12#N#L. C. Racusen, R. B. Colvin, K. Solez et al., “Antibody-mediated rejection criteria—an addition to the Banff '97 classification of renal allograft rejection,” American Journal of Transplantation, vol. 3, no. 6, pp. 708–714, 2003. View at: Publisher Site | Google Scholar#N#See in References#N#]. This raises a concern that additional evidence is needed to diagnose AMR such as quantification of DSA or other morphologic feature consistent with AMR on pathology. However it should be noted that Regele and colleagues presented data from 1 year after AMR that kidney transplant patients with positive C4d had higher incidence of graft loss and elevation of serum creatinine [ 14#N#H. Regele, M. Exner, B. Watschinger et al., “Endothelial C4d deposition is associated with inferior kidney allograft outcome independently of cellular rejection,” Nephrology Dialysis Transplantation, vol. 16, no. 10, pp. 2058–2066, 2001. View at: Google Scholar#N#See in References#N#]. After the Banff meeting in 2001 it was determined that AMR has 3 cardinal features upon biopsy findings. (1) Acute tubular injury; neutrophils and/or mononuclear cells in peritubular capillaries and/or glomeruli, and/or capillary thrombosis; or arteritis/fibrinoid necrosis in the intima along with intramural/transmural arterial inflammation. (2) C4d evidence for antibody action and/or immunoglobulin in peritubular capillaries, immunoglobulin and complement in arterial fibrinoid necrosis. (3) Anti-HLA antibody (DSA) circulation in serum or other antidonor endothelial antigens.
What is AMR in kidney transplant?
Antibody-mediated rejection (AMR) is a major cause of late kidney transplant failure. It is important to have an understanding of human-leukocyte antigen (HLA) typing including well-designed studies to determine anti-MHC-class-I-related chain A (MICA) and antibody rejection pathogenesis. This can allow for more specific diagnosis and treatment which may improve long-term graft function. HLA-specific antibody detection prior to transplantation allows one to help determine the risk for AMR while detection of DSA along with a biopsy confirms it. It is now appreciated that biopsy for AMR does not have to include diffuse C4d, but does require a closer look at peritubular capillary microvasculature. Although plasmapheresis (PP) is effective in removing alloantibodies (DSAs) from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment. Also used are agents targeted for plasma cells, B cells, and the complement cascade which are bortezomib rituximab and eculizumab, respectively.
What is the role of the spleen in the body?
The spleen is the largest lymphoid organ in the body and has been found to play a role in alloantibody generation . Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as positive crossmatches, however it has been found to surprisingly treat AMR refractory to treatment [ 22#N#B. Kaplan, T. Jie, R. Diana et al., “Histopathology and immunophenotype of the spleen during acute antibody-mediated rejection: case report,” American Journal of Transplantation, vol. 10, no. 5, pp. 1316–1320, 2010. View at: Publisher Site | Google Scholar#N#See in References#N#]. There are a few case studies, one in particular where abundant clusters of CD138+ plasma cells were found upon review of pathology of the spleen [ 22#N#B. Kaplan, T. Jie, R. Diana et al., “Histopathology and immunophenotype of the spleen during acute antibody-mediated rejection: case report,” American Journal of Transplantation, vol. 10, no. 5, pp. 1316–1320, 2010. View at: Publisher Site | Google Scholar#N#See in References#N#]. Usually in traumatic splenectomy controls, CD138+ cells are found in 1% of the spleen. This patient had refractory AMR without improvement in her serum creatinine. She had been treated with PP/IVIG and then underwent emergent splenectomy. Immediately afterward, there was improvement in her renal function and rapid drop in DR51 antibodies [ 22#N#B. Kaplan, T. Jie, R. Diana et al., “Histopathology and immunophenotype of the spleen during acute antibody-mediated rejection: case report,” American Journal of Transplantation, vol. 10, no. 5, pp. 1316–1320, 2010. View at: Publisher Site | Google Scholar#N#See in References#N#]. The mechanism of action is not entirely clear as to why splenectomy treats AMR, but several case reports have indicated that it could be a potential treatment for refractory AMR to PP/IVIG. It is not certain whether the CD138+ cells found in the spleen had produced anti-DR51 antibodies in this particular case, but provides a novel insight for further studies in the role of the spleen with AMR. Of course, splenectomy has risks associated with it which include increased risk of infections and the risks associated with surgery. Therefore these risks must be discussed with the patient before proceeding, as this is not a conventional treatment for AMR. There is lifelong risk with encapsulated microorganisms; therefore patients must receive Haemophilus influenza vaccine, pneumococcal, and meningococcal vaccines.
What is IVIG used for?
IVIG is used in combination with PP to neutralize antibodies and potentially block complement activity as well as agents used for suppression of antibody ( cacineurin inhibitors, mycophenolate, or rituximab). Immunoadsorption (IA) is a substance derived from the Cowan strain of Staphylococcus aureus.
Which cell type is involved in the class II MHC?
Class I major histocompatibility complex (MHC) molecule processing and loading of peptides occurs in all nucleated cells, where class II MHC molecule involves primarily B cells, macrophages, and dendritic cells by method of endocytosis and phagocytosis.
Is plasmapheresis effective for DSAs?
Although plasmapheresis (PP) is effective in removing alloantibodies (DSAs) from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment.
Can you get sensitized prior to a transplant?
Sensitization prior to transplant can occur by pregnancy or blood transfusions. Previous transplantation can also sensitize patients against HLA molecules. Blood transfusions can induce humoral immunity by formation of HLA alloantibodies and are more likely to occur in individuals who have been previously pregnant.
Antibody-Mediated Rejection (AMR) Overview
Acute antibody-mediated rejection (AMR) or acute humoral rejections occurs in patients who are pre-sensitized or who develop a threshold level of de novo donor specific antibody (DSA) at any point after transplantation. There are no specific clinical features that distinguish acute T-cell-mediated rejection (TCMR) from acute AMR.
Types of Antibody-Mediated Rejection (AMR)
Antibodies directed against donor antigen can cause different types of rejection that can vary in acuity and severity. Following are different types of antibody-mediated rejection:
Signs and Symptoms of Antibody-Mediated Rejection (AMR)
Antibody-mediated rejection (AMR) patients can be asymptomatic or can have the following symptoms:
Antibody-Mediated Rejection (AMR) Diagnosis
The diagnosis of AMR remains a challenge and requires the correlation of clinical, radiologic, pathologic, serologic, and microbiologic findings. Key diagnostic criteria include biopsy findings consistent with AMR, positive immuno-histochemical staining for complement 4d (C4d), and detection of circulating DSAs.
What is chronic AMR?
Chronic AMR is a B-cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ. Based on this pathophysiologic condition, rituximab, IVIG, and bortezomib have been used as treatment for chronic AMR recently. However, till now, there is no standardized treatment for late/chronic AMR. The strategies that can effectively reverse early AMR do not work as well in late episodes; thus, an ounce of prevention is really worth a pound of cure [ 32#N#J. A. Bradley, W. M. Baldwin, A. Bingaman et al., “Antibody-mediated rejection—an ounce of prevention is worth a pound of cure,” American Journal of Transplantation, vol. 11, no. 6, pp. 1131–1139, 2011. View at: Publisher Site | Google Scholar#N#See in References#N#]. As late AMR usually is caused by de novo DSA, posttransplant HLA alloantibody monitoring is of great importance for the prevention of antibody-mediated allograft injury [ 33#N#C. Morath, G. Opelz, M. Zeier, and C. Susal, “Prevention of antibody-mediated kidney transplant rejection,” Transplant International, vol. 25, pp. 633–645, 2012. View at: Google Scholar#N#See in References#N#]. Prevention of nonadherence and insufficient immunosuppression are additional important issues in the prevention of antibody-mediated allograft injury, as these factors are risk factor for late AMR. A recent study based on ABO-incompatible renal transplantation revealed that B-cell depletion protocols, such as splenectomy or rituximab administration, could reduce chronic AMR after kidney transplantation. Finally, the triple immunosuppressants protocol including mycophenolic acid, tacrolimus, and steroid can control antidonor antibody production in renal allograft recipients with chronic rejection [ 34#N#T. P. Theruvath, S. L. Saidman, S. Mauiyyedi et al., “Control of antidonor antibody production with tacrolimus and mycophenolate mofetil in renal allograft recipients with chronic rejection,” Transplantation, vol. 72, no. 1, pp. 77–83, 2001. View at: Publisher Site | Google Scholar#N#See in References#N#] and seem to be superior to others in treating AMR [ 35#N#Q. Sun, Z.-H. Liu, Z. Cheng et al., “Treatment of early mixed cellular and humoral renal allograft rejection with tacrolimus and mycophenolate mofetil,” Kidney International, vol. 71, no. 1, pp. 24–30, 2007. View at: Publisher Site | Google Scholar#N#See in References#N#, 36#N#Q. Sun, Z.-H. Liu, G. Yin et al., “Tacrolimus combined with mycophenolate mofetil can effectively reverse C4d-positive steroid-resistant acute rejection in Chinese renal allograft recipients,” Nephrology Dialysis Transplantation, vol. 21, no. 2, pp. 510–517, 2006. View at: Publisher Site | Google Scholar#N#See in References#N#]; however, whether it can prevent the development of late AMR is not clear, see Table 2.
What causes AMR?
AMR is caused by anti-donor-specific antibodies, mostly anti-HLA antibodies [ 8#N#R. B. Colvin, “Antibody-mediated renal allograft rejection: diagnosis and pathogenesis,” Journal of the American Society of Nephrology, vol. 18, no. 4, pp. 1046–1056, 2007. View at: Publisher Site | Google Scholar#N#See in References#N#, 9#N#L. C. Racusen, R. B. Colvin, K. Solez et al., “Antibody-mediated rejection criteria—an addition to the Banff 97 classification of renal allograft rejection,” American Journal of Transplantation, vol. 3, no. 6, pp. 708–714, 2003. View at: Publisher Site | Google Scholar#N#See in References#N#]. Some non-HLA antibodies also have been reported to induce AMR in rare cases. The phenotype of AMR ranges from hyperacute rejection, acute AMR, and chronic AMR. The diagnosis of AMR depends on typical histological lesions, C4d staining, and serum DSA detection. C4d, a protein from the classical complement activation cascade that remains attached to the site of complement activation, is regarded as a diagnosis marker for AMR. The introduction of C4d as marker of AMR aroused an ever-increasing interest in recognizing mechanisms of allograft rejection. However, C4d has several limitations in the diagnosis of AMR. For instance, it can be found in the majority of grafts with stable function in ABO-incompatible transplantations. On the other hand, a group of C4d-negative AMR has been recognized based on endothelial gene expression [ 10#N#B. Sis, G. S. Jhangri, S. Bunnag, K. Allanach, B. Kaplan, and P. F. Halloran, “Endothelial gene expression in kidney transplants with alloantibody indicates Antibody-mediated damage despite lack of C4d staining,” American Journal of Transplantation, vol. 9, no. 10, pp. 2312–2323, 2009. View at: Publisher Site | Google Scholar#N#See in References#N#, 11#N#B. Sis and P. F. Halloran, “Endothelial transcripts uncover a previously unknown phenotype: C4d-negative antibody-mediated rejection,” Current Opinion in Organ Transplantation, vol. 15, no. 1, pp. 42–48, 2010. View at: Publisher Site | Google Scholar#N#See in References#N#]. About 40% of patients with endothelial-associated transcripts expression and chronic AMR features demonstrated no C4d staining. Similarly, C4d staining is only positive in about half of patients with transplant glomerulopathy [ 12#N#F. G. Cosio, J. M. Gloor, S. Sethi, and M. D. Stegall, “Transplant glomerulopathy,” American Journal of Transplantation, vol. 8, no. 3, pp. 492–496, 2008. View at: Publisher Site | Google Scholar#N#See in References#N#, 13#N#Q. Sun, X. Huang, S. Jiang, C. Zeng, and Z. Liu, “Picking transplant glomerulopathy out of the CAN: evidence from a clinico-pathological evaluation,” BMC Nephrology, vol. 13, article 128, 2012. View at: Google Scholar#N#See in References#N#], which is a special form of chronic AMR. C4d-positive and -negative AMR share similar degrees of glomerulitis and peritubular capillaritis, similar frequencies of concurrent cell-mediated rejection, and both may occur early or late after transplantation, thus needing to be treated equally [ 14#N#M. Haas, “Pathology of C4d-negative antibody-mediated rejection in renal allografts,” Current Opinion in Organ Transplantation, vol. 18, pp. 319–326, 2013. View at: Google Scholar#N#See in References#N#].
What is the difference between late AMR and early AMR?
Early AMR are usually correlated with sensitization, pre-existing alloantibodies, and rapid graft dysfunction and are usually easy to be controlled; while late AMR mostly correlated with withdrawal or reduction of immunosuppressants, noncompliance with immunosuppressive therapy.
What causes graft loss after transplantation?
Antibody-mediated rejection (AMR) is an important cause of graft loss after organ transplantation. It is caused by anti-donor-specific antibodies especially anti-HLA antibodies. C4d had been regarded as a diagnosis marker for AMR. Although most early AMR episodes can be successfully controlled or reversed, late and chronic AMR remains the leading cause of late graft loss. The strategies which work in early AMR have limited effect on late/chronic episodes. Here, we reviewed the lines of evidence that late/chronic AMR is the leading cause of late graft loss, characteristics of late AMR, and current strategies in managing late/chronic AMR. More effort should be put on the management of late/chronic AMR to make a better long term graft survival.
Is AMR involved in heart transplant?
AMR in Other Organ Transplantation . AMR is also involved in other organ transplantation, especially for heart transplantation. DSA binding to the heart allograft causes myocardial injury predominantly through immune complex activation of the classical pathway of the complement cascade [ 65.
Can AMR be reversed?
Although most early AMR episodes can be successfully controlled or reversed, late and chronic AMR remains the leading cause of late graft loss. The strategies which work in early AMR have limited effect on late/chronic episodes.
Is graft failure rare?
Similarly, they found that graft failure was rare after T-cell-mediated rejection and acute kidney injury while was common after AMR or glo merulonephritis. The majority of graft loss had evidence of AMR by the time of failure.
