Bay Biosciences provides high quality, clinical grade bio-specimens, cryogenically preserved sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid samples from patients diagnosed with antibody-mediated rejection (AMR).
The sera (serum), plasma and PBMC biofluid specimens are processed from patient’s peripheral whole-blood using customized collection and processing protocols. The antibody-mediated rejection (AMR) bio-specimens are collected from unique patients diagnosed with antibody-mediated rejection (AMR) and are provided to a valued pharmaceutical customer for research, diagnostics, discovery and drug development.
Detailed clinical data, cold agglutinin disease patients history, symptoms, complete blood count (CBC), elevated biomarker levels, genetic and metabolic information, histopathological findings, annotations associated with antibody-mediated rejection (AMR) patient’s specimens is provided to a valued customer for research, development and drug discovery. The antibody-mediated rejection (AMR) sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid are processed from patients peripheral whole-blood using customized collection and processing protocols.
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. 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.
Antibody-mediated rejection (AMR) is caused by donor-specific antihuman leukocyte antigen antibodies (DSA’s). Antibody-mediated rejection (AMR) is divided into hyper acute (occurring intraoperatively or within 24 hours of surgery), acute (often mimicking acute cellular rejection), and chronic (potentially manifesting as an occult cause of CLAD) forms. These DSA’s antibodies, which may develop before or after transplantation, bind to target antigens and activate the complement system. Antibody-mediated rejection (AMR), also termed humoral rejection, is one of the most important causes of allograft dysfunction and loss accounting for up to 76% of death-censored graft failures beyond the first year of organ transplantation. According to current evidence, B cell and plasma cell activation results in the generation of donor-specific antibodies (DSAs), which bind to human leukocyte antigen (HLA) or non-HLA molecules expressed on endothelial cells within the renal allograft.
AMR is caused by anti-donor-specific antibodies, mostly anti-HLA antibodies. Some non-HLA antibodies also have been reported to induce AMR in rare cases. The phenotype of AMR ranges from hyper acute 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.
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:
Hyper Acute Antibody-Mediated Rejection
Hyper acute antibody-mediated rejection (AMR) occurs due to preformed donor specific antibodies (DSA) present in high titers and presents as graft failure that can occur within minutes (but sometimes may be delayed for a few days) after transplantation. The occurrence of hyper acute antibody-mediated rejection is extremely rare because of the universal adoption of pre-transplantation cross-matching. The histopathology is characterized by features of severe endothelial and arterial injury manifested as arteritis (often transmural), interstitial edema, and severe cortical necrosis, with almost all cases requiring allograft nephrectomy. Most of the initial cases were reported in patients with a history of previous transplantation or in multiparous women, suggesting the role of sensitization and preformed antibodies. Studies have shown that high number of patients who had pre-transplant positive crossmatch had immediate graft failure compared with much less graft failures in patients without a positive crossmatch.
Acute antibody-mediated rejection (AMR)
Acute antibody-mediated rejection (AMR) is characterized by graft dysfunction manifesting over days and is a result of DSAs, that may either be preformed or develop de novo after transplantation. Acute AMR occurs in about 5% to 7% of all kidney transplants and is responsible for 20% to 48% of acute rejection episodes among positive crossmatch patients. Allograft dysfunction with resultant creatinine elevation may not be present in all cases of AMR. Histopathology in the acute antibody-mediated rejection (AMR) patients is related to endothelial injury mediated by antibodies but is less severe than that seen in hyper acute rejections. Biopsy often shows endothelial cell swelling, neutrophilic infiltration of glomeruli and peritubular capillaries, fibrin thrombi, interstitial edema, and hemorrhage. However, in some of these rejections, acute tubular necrosis may be the only feature observed. The identification of these AMRs has become easier with the development of C4d-staining in biopsies and improved methods of antibody detection.
Chronic Antibody-Mediated Rejection
Antibodies can mediate chronic allograft injury which is characteristically seen as transplant glomerulopathy (TG) on kidney biopsies . TG (also known as or chronic allograft glomerulopathy) is characterized by glomerular mesangial expansion and capillary basement membrane (BM) duplication, seen as basement membrane double contouring or splitting. Similarly, the peritubular capillary (PTC) basement membrane also shows changes, but these are seen mostly on electron microscopy sections as basement membrane multilayering. Clinically, the manifestations range from patients being asymptomatic in the early stages to having nephrotic range proteinuria, hypertension, and allograft dysfunction in the advanced stages. Progression can sometimes be fairly rapid, especially with ongoing acute AMR, resulting in graft failure within months . The prevalence of TG in protocol biopsies has varied between 5% at 1 yr to 20% at 5 years.
Signs and Symptoms of Antibody-Mediated Rejection (AMR)
Antibody-mediated rejection (AMR) patients can be asymptomatic or can have the following symptoms:
- Allograft dysfunction
- Hypoxemia
- Cough
- Fever
- Malaise
- Shortness of breath(Dyspnea)
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. 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 allograft dysfunction, other potential causes of the dysfunction such as infection need to be excluded.
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Bay Biosciences provides human tissue samples (human specimens) from diseased and normal healthy donors; including peripheral whole-blood, amniotic fluid, bronchoalveolar lavage fluid (BAL), sputum, pleural effusion, cerebrospinal fluid (CSF), serum (sera), plasma, peripheral blood mononuclear cells (PBMC’s), saliva, Buffy coat, urine, stool samples, aqueous humor, vitreous humor, kidney stones, renal calculi, nephrolithiasis, urolithiasis and other bodily fluids from most diseases including cancer. We can also procure most human bio-specimens and can do special collections and requests of human samples that are difficult to find. All our human tissue samples are procured through IRB approved clinical protocols and procedures.
In addition to the standard processing protocols Bay Biosciences can also provide human plasma, serum, PBMC bio-fluid samples using custom processing protocols, you can buy donor specific sample collections in higher volumes and specified sample aliquoting from us. Bay Biosciences also provides human samples from normal healthy donors, volunteers, for controls and clinical research, contact us Now.
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