Antibody-Mediated Rejection (AMR) Samples

Bay Biosciences provides high-quality, matched fresh frozen sera (serum),  plasma, and peripheral blood mononuclear cells (PBMC) bio-fluids from patients diagnosed with antibody-mediated rejection (AMR).

Moreover, the sera (serum), plasma and PBMC bio-fluids are processed from antibody-mediated rejection (AMR) patient’s peripheral whole-blood using customized collection and processing protocols.

In addition, the matched bio-fluids are collected from unique patients with antibody-mediated rejection (AMR) and are provided to a valued pharmaceutical customer for research, development and drug discovery.

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.

Furthermore, there are no specific clinical features that distinguish acute T-cell-mediated rejection (TCMR) from acute AMR. In addition, the histologic findings in acute AMR are often characteristic but quite variable and may resemble acute tubular injury or thrombotic microangiopathy (TMA) and, moreover,** may be obscured by features of TCMR.

Now, Let’s Discuss the Role of DSA’s

Antibody-mediated rejection (AMR) is caused by donor-specific antihuman leukocyte antigen antibodies (DSA’s). Specifically, 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.

Notably, these DSA’s antibodies, which may develop before or after transplantation, bind to target antigens and activate the complement system. Consequently, 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.

Ultimately, according to current evidence, B cell and plasma cell activation results in the generation of donor-specific antibodies (DSAs).

HLA’s

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. Additionally, researchers have also reported that some non-HLA antibodies induce AMR in rare cases. Consequently, the phenotype of AMR ranges from hyper acute rejection, acute AMR, to chronic AMR.

The diagnosis of AMR, therefore, depends on typical histological lesions, C4d staining, and serum DSA detection. Notably, researchers regard C4d, a protein from the classical complement activation cascade that remains attached to the site of complement activation, as a diagnostic marker for AMR.

Furthermore, the introduction of C4d as a marker of AMR aroused an ever-increasing interest in recognizing mechanisms of allograft rejection. However, it is important to note that C4d has several limitations in the diagnosis of AMR. For instance, researchers can find it 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). Moreover, interstitial edema, and severe cortical necrosis, with almost all cases requiring allograft nephrectomy.

Doctors reported most of the initial cases in patients with a history of previous transplantation. And, 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)

In fact, 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. Moreover, 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 doctors characteristically see as transplant glomerulopathy (TG) on kidney biopsies. Doctors characterize TG (also known as chronic allograft glomerulopathy) by glomerular mesangial expansion and capillary basement membrane (BM) duplication.

This researchers see as basement membrane double contouring or splitting. Similarly, the peritubular capillary (PTC) basement membrane also shows changes. However, experts mostly observe these 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:

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. Such as, 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. Healthcare professionals require two of the three criteria for a probable AMR diagnosis and one of the three criteria 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 measurable allograft dysfunction occurs, you need to exclude other potential causes of the dysfunction such as infection.

Biospecimens

Bay Biosciences is, indeed a global leader in providing researchers with high quality, clinical grade, fully characterized human tissue samples, bio-specimens, and human bio-fluid collections.

Specifically, aamples available include cancer (tumor) tissue, cancer serum, cancer plasma, cancer, peripheral blood mononuclear cells (PBMC) and human tissue samples from most other therapeutic areas and diseases.

Moreover, Bay Biosciences maintains and manages its own biorepository, the human tissue bank (biobank) consisting of thousands of diseased samples (specimens) and from normal healthy donors available in all formats and types.

In fact, our biobank procures and stores fully consented, de-identified and institutional review boards (IRB) approved human tissue samples and matched controls.

Additionally, all our human tissue collections, human specimens and human bio-fluids are provided with detailed, samples associated patient’s clinical data.

In particular, critical patient’s clinical data includes information relating to their past and current disease, treatment history, lifestyle choices, biomarkers, and genetic information.

Moreover, researchers find patient’s data extremely valuable and use it to help identify new effective treatments (drug discovery & development) in oncology, and other therapeutic areas and diseases.

Specifically, Bay Biosciences banks wide variety of human tissue samples and biological samples, including cryogenically preserved at – 80°C.

For example fresh frozen tissue samples, tumor tissue samples, formalin-fixed paraffin-embedded (FFPE), tissue slides, with matching human bio-fluids, whole blood and blood-derived products such as serum, plasma and PBMC.

Furthermore, Bay Biosciences is a global leader in collecting and providing human tissue samples according to the specified requirements and customized, tailor-made collection protocols.

Therefore, please contact us anytime to discuss your special research projects and customized human tissue sample requirements.

Types of Biospecimens

Bay Biosciences provides human tissue samples (human specimens) from diseased and normal healthy donors which includes:

  • Firstly, Peripheral whole-blood
  • Secondly, Amniotic fluid
  • Third, Bronchoalveolar lavage fluid (BAL)
  • Moreover, Sputum
  • Furthermore, Pleural effusion
  • Next, Cerebrospinal fluid (CSF)
  • Also, Serum (sera)
  • Likewise, Plasma
  • In addition, Peripheral blood mononuclear cells (PBMC)
  • For example, Saliva
  • Also, Buffy coat
  • Moreover, Urine
  • Furthermore, stool samples
  • Next, Aqueous humor
  • Likewise, Vitreous humor
  • Lastly, Kidney stones (renal calculi)
  • Finally, Other bodily fluids from most diseases including cancer.

Moreover, we can also procure most human bio-specimens, furthermore; we offer special collections and requests for 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, and PBMC bio-fluid samples using custom processing protocols. Additionally you buy donor-specific collections in higher volumes and specified sample aliquots from us.

Furthermore, Bay Biosciences also provides human samples from normal healthy donors; volunteers, for controls and clinical research, contact us Now.

 

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