| Renal allograft transplantation is a clinically effective means to treat end-stage renal disease. Pathological change induced by allograft rejection causing abnormal renal function remains the current, primary challenge in the field. Recently, due to the widespread use of a new generation of immunosuppressants, the clinical presentation caused by renal allograft rejection has become increasingly atypical. Relying solely on clinical symptoms and signs, at times, does not suffice to make an accurate diagnosis to account for dysfunctions of the transplanted kidney. Thus, an examination of renal biopsy samples has become a critical means in the diagnosis and differential diagnosis of renal dysfunction and failure. Despite the use of reasonable combined immunosuppressants, there remains 40% of renal transplantation resulting in post-operative acute rejection. Although researchers have clearly recognized that immunological rejection is a key factor to the survival of the transplanted kidney, because of the complexity of the mechanism and triggers of the rejection, the process remain unclear.Due to the limited patient cases, the recognition of pathology of biopsies from renal transplantation progresses slowly. Knowledge regarding the specific mechanism of action of renal transplant rejection is even less available. Therefore, this study, firstly, summarizes 66 clinical cases of dysfunction of transplanted kidney in the past year examined by renal puncture. Upon this basis, 44 acute rejection samples out of 66 have been chosen to be analyzed through immunohistochemistry, in order to systematically observe the type anddistribution of infiltrated immunological cells in different rejection situations. The mechanism of action of renal allograft rejection will be investigated. This research study is divided into two sections.Section I: Morphological change in 66 cases of renal transplant dysfunction The 66 biopsy samples from renal grafts were collected from patients at the First Hospital of Jinlin University, Organ Transplantation Center, whom following allograft renal transplantation, developed abnormal clinical presentations. Of these, 44 are male, 22 are female; the mean age is 43.9 years. Renal puncture samples were fixed in 10% formalin, embedded in paraffin, and cut in 2μm sections. Standard staining techniques were used on samples, namely H&E, PAS staining, Masson's trichrome, and periodic-acid-methanamine-silver (PAMS). Part of the samples has been stained for IgG, IgA, IgM. C3, C4, and fibrinous immunological fluorescein staining. Results indicate that among the 66 cases in total, 54 cases of renal biopsies were diagnosed pathologically as rejections (i.e. 81.82% of total). These rejections differ between acute or chronic, without observed immediate or delayed antibody-mediated rejection, and without observed change typical blood vessel such as fibrinoid necrosis, mesarteritis, or panarteritis.Among the 66 cases of renal biopsies, 2 had normal transplanted kidneys. There were 44 cases of acute rejections, 10 cases of chronic rejections, 5 cases of nephron tubular damage, 2 cases of acute and 1 case of chronic cyclosporinepoisoning, and 2 cases of tubular change without observed evident rejection. Acute rejection accounts for 66.67% of observed rejections. These include: 10 cases of marginal changes (suspected acute rejection), 20 cases of acute cellular rejection Class I (Banf IA), 6 cases of class II-III (Banf IB), 1 case of acute vascular rejection (Banf IIA), and 1 mixed case of acute cellular and vascular rejection. It is of paramount importance to the diagnosis of allograft renal transplantation rejections to be able to recognize various degrees and scopes of lymph and characteristics of monoclonal invasion. The pathology of renal puncture biopsies can provide reliable treatment and prognostic evidence. Section II Cellular Observations in Acute rejectionAmong 44 patient cases of acute rejection out of 66 patient cases in total, there are 16 cases with marginal change (suspected acute rejection reaction), 20 were class I acute cellular or tubular-interstitial rejection, 6 were class II-III acute cellular rejection, and 1 case of acute vascular rejection, and 1 case of both cellular and vascular rejection. Four markers, CD8 (cytotoxic T-lymphocytes with with rejection capability), CD20 (pre-B cell end stage and pre-plasmocyte B lymphocytes), CD79A (pre-B cell from beginning until plasmocyte stage) and CD 68 (macrophages), using S-P immunohistochemistry, were used to stain T and B cells as well as macrophage invasion from post-transplantation kidneys which underwent subsequent rejection.Results indicate that in acute cellular rejection, including marginal patientcases, the main type of lymphocytes in the interstitium is CD8+ cell (cytotoxic T cell) and CD 20+ (pre-B cell). As the severity of rejection increases, the percentage of CD8+ cells increases. The percentage of CD8+ T-cells of acute cellular rejection of class II-III reaches 44.167%±11.583, which is significantly higher than that of CD8+ cells of class I, which reaches 18.725%±12.220, and that of marginal rejection patient cases is 14.031%±12.705. The percentage of CD8+ T-cells of acute cellular rejection of class II-III is significantly higher than that of CD8+ cells of class I and marginal rejection patient cases (P<0.01). Correspondingly, as the degree of severity of rejection increases, the percentage of CD20+ cells decreases. The percentage of CD20+ B cells in class II-III is16.534%±26.952, in class I is 38.250%±24.327, and in marginal cases is 45.406%±21.035 (P<0.05). At the same time, in the development of tubulitis developed, lymphocytes inside the peritubular walls are mainly CD8+ cells. The percentage of CD 68+ cells did not vary significantly with different degrees of rejection reactions. This result support and explain that T-cell immunological reaction is the basis of acute cellular rejection, and is also one of the causes of the mediation of immune injury.In the single case of acute vascular rejection, the pathological changes are manifested primarily as the invasion of cells into the walls and the endothelium of blood vessels. The intima shows invasion of inflammatory cells, where CD68+ macrophage was the main type of invading cell, and no CD8+, CD 20+and CD79A+ cells were observed. In acute vascular rejection, the main cell type that invaded vessel endothelium is the macrophage. In the other case of acute mixed rejection (cellular and vascular), the vessel endothelium invasion demonstrated the immune markers CD8, CD20, and CD79A as negative, and CD68 as positive in macrophages. The discovery of this phenomenon will hopefully provide a reference to the mechanism of immunological rejection reaction in allograft renal transplantation.In summary, in the renal biopsy of dysfunctional transplanted kidneys, the acute cellular rejection is the main responsible pathological change. Recognizing the pathology of graft rejection has important clinical significant. In acute cellular rejection, the lymphocytes which invaded the interstitium are mainly CD8+ and CD 20+ cells. As well, as the degree of severity of immunological reaction increases, the percentage of CD8+ cells increases, indicating that the T-cell mediated immune reaction is the basis of acute cellular rejection. In the acute vascular case of rejection, the invasion into blood vessel intima involves mainly CD 68+ macrophages, contrary to the common conception that lymphocytes are involved.
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