Abstract
Currently, the diagnosis of kidney allograft rejection relies on individual histological assessments made by expert pathologists according to the Banff classification. In this study, we applied new Computer-Assisted System Technology (newCAST™) by Visiopharm® with the aim of identifying and quantifying the immune cells in inflammatory infiltrates. We searched for distinctive cellular profiles that could be assigned to each rejection category of the Banff schema: antibody-mediated rejection (active and chronic active), borderline, T cell-mediated rejection (TCMR), and mixed rejection. This study was performed with 49 biopsy samples, 42 from patients with rejection and 7 from patients with clinical signs of dysfunction but an absence of histological findings of rejection. Plasma cells, B and T lymphocytes, natural killer cells, and macrophages, with a special focus on the M1 and M2 subsets, were studied. A major difference among the Banff rejection groups was in the total amount of cells/mm2 tissue. Principal component analysis identified some distinctive associations. The borderline category grouped with CD4+ lymphocytes and M1 macrophages, and active antibody-mediated rejection (aAMR) clustered with natural killer cells. Despite these findings, the search for characteristic profiles linked to the rejection types proved to be a very difficult task since the cellular composition varied significantly among individuals within the same diagnostic category. The results of this study will be analyzed from the perspective of reconciling the classic way of diagnosing rejection and the immune situation “in situ” at the time of diagnosis.
Highlights
Clinical and subclinical rejections are the major causes of kidney allograft loss, and some types of rejection are difficult to diagnose and are detected late after the onset of the rejection process
Among 78 biopsies corresponding to 57 kidney transplants, 61 fulfilled the diagnostic criteria for different rejection categories and were distributed as follows: 15 active antibody-mediated rejection (aAMR) biopsies, 18 chronic active antibodymediated rejection (cAMR) biopsies, 17 BL biopsies, 4 T cell-mediated rejection (TCMR) biopsies, and 7 mixed rejection (MR) biopsies
The remaining 17 biopsies, performed due to renal dysfunction, did not show histological signs of rejection and were used as the non-rejection group (NR). All these biopsies were classified with the Banff schema, but only 49 of them were analyzed with newCASTTM due to a shortage of tissue samples
Summary
Clinical and subclinical rejections are the major causes of kidney allograft loss, and some types of rejection are difficult to diagnose and are detected late after the onset of the rejection process. Some of the categories are well-characterized, but others are challenging Among these categories, the process classified as borderline is not well-defined. At the first Banff meeting, this category was defined as mild focal interstitial inflammation and tubulitis with histological findings suggestive of a very mild acute rejection. The question is whether the borderline category should be eliminated or at least redefined. With this purpose in mind, during the last Banff meeting in Barcelona, a series of histological and molecular studies were proposed to better organize this classification system [3]
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