International Journal of Organ Transplantation Medicine
Volume:10 Issue: 2, Spring 2019

Monitoring of chemokines, CXCL9 and CXCL10, in serum may present a non-invasive detection method for rejection. To investigate the relationship between urinary levels of CXCL9 and CXCL10 and graft function following renal transplantation. 75 living-related donor renal transplant recipients were studied. Urinary levels of chemokines were collected pre-operatively, on post-operative 1st day, 7th day, 1st month, 3rd month, and at the time of rejection. Chemokines levels were assayed using and enzyme-linked immunosorbent assay. Clinical variables were monitored. 10 (15%) patients had biopsy-proven rejection during the follow-up period. The urinary CXCL9 level in those with rejection was significantly higher than that in those with non-rejection group at the 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.002). The urinary CXCL10 level was also significantly higher in those with rejection compared with non-rejection group at 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.001). Serum creatinine level was strongly correlated with the urinary CXCL9 and CXCL10 levels at the time of rejection (r=0.615, p=0.002; and r=0.519, p=0.022, respectively). Among those with T cell-mediated rejections the mean urinary CXCL10 level increased to as high as 258.12 ng/mL. Urinary CXCL9 and CXCL10 levels might have a predictive value for T cell-mediated rejection in early post-transplantation period. Measurement of urinary CXCL9 and CXCL10 levels could provide an additional tool for the diagnosis of rejection.

Mesenchymal stem cells are one of the most interesting cell sources used in regenerative medicine. In the present study, we isolated and characterized the mesenchymal stem cells from various compartments of human adipose tissue and tunica adventitia layer of the arteries. Tissue explant culture was done from various compartments of the human adipose tissue and tunica adventitia layer of the arteries, including adipose tissue far from the vessels, perivascular tissues that are completely attached to the vessels, and tunica adventitia layer of the arteries. After the cell culture, characterization of the cells was determined at 3rd–5th passages. Flow cytometry was performed for antigen expression analysis of CD34, CD45, CD44, CD90, CD29, CD73, and CD105. For the evaluation of cell differentiation potential, adipogenic and osteogenic differentiation was conducted under appropriate protocols. The cells were positive for CD44, CD90, CD29, and CD73 and negative for CD34, CD45, and CD105. Adipogenic and osteogenic differentiation potentials were different among the cells from various compartments. The cells derived from perivascular tissue demonstrated better adipogenic and osteogenic differentiation. It is essential to characterize the cells from different tissues and compartments for different purposes in regenerative medicine.

Kidney transplantation is the most effective and optimal treatment for end-stage renal disease. To investigate the association between serially measured ultrasound indices during the early post-operative period to determine severe acute tubular necrosis (ATN) in kidney allografts. In a prospective study, we assessed sonographic renal indices including interlobar arteries peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI), pulsatility index (PI), power doppler grading (PDG), acceleration time (AT), and renal volume on the 3rd and 9th days after kidney transplantation in 46 adult recipients who had no other significant complications except ATN. Biopsies were performed in patients with prolonged delayed graft function (DGF) to exclude other pathologies, especially acute rejection. 12 (20%) recipients experienced biopsy-proven severe ATN. The differences in the ultrasound indices and their measured discrepancies on the 1st and 2nd examinations between the groups were not statistically significant except for the 1st examined RI (p=0.029) and PI (p=0.04). No patient had PDG of >2. The first RI, with a cut-off value of 0.66, had a sensitivity of 91.7% and a specificity of 50% for predicting severe ATN (area under the ROC curve = 0.71). To compensate for the low specificity of this index, we suggest using the first PDG scale of equal to 2 with a specificity of 85.3%. Overall sensitivity, specificity, and positive and negative predictive values in established severe ATN throughout early post-operative days for a 3rd day RI >0.66 and PDG = 2, were 38%, 92.5%, 64.1%, and 80.9%, respectively. The RI and the PDG measured on the 3rd day after renal transplantation are useful indices for the diagnosis of established severe ATN in kidney allografts. Furthermore, donor characteristics, post-harvesting organ preservation status, main renal vascular anastomosis, and early post-operative recipient’s clinical situations may also influence the incidence of severe ATN. Although the 1st ultrasound examination on the 3rd day in early post-transplantation provides important diagnostic and prognostic information, repeated assessment about one week later provides no more valuable information.

Dysregulated expression of co-stimulatory molecules is one of the immune escape mechanisms employed in hematologic malignancies like acute myeloid leukemia (AML). To evaluate the expression of the CD28 and CTLA-4 molecules in 62 adults with de novo AML and its correlation with the development of acute graft vs host disease (GVHD) after hematopoietic stem-cell transplantation. The relative expression of CD28 and CTLA-4 was measured by quantitative SYBR Green real-time PCR method in a group of patients and controls as well as different risk groups (high, intermediate and favorite risk), M3 vs non-M3 and GVHD vs non-GVHD patients. The mRNA expression of CD28 (7.9-fold) and CTLA-4 (5.7-fold) was significantly increased in AML patients compared with healthy controls (p=0.006 and 0.02, respectively). Although the mean expression of both CD28 and CTLA-4 was increased in high-risk group compared with low-risk and intermediate- risk groups, the difference was not statistically significant. Also, the mean expression of the CTLA-4, but not CD28, was significantly higher in M3 patients compared with non-M3 ones (p<0.001). The expression of CD28 was upregulated in GVHD patients, while the expression of CTLA-4 was slightly lower in GVHD patients compared with non-GVHD patients, though the difference was not statistically significant. There was no significant correlation between the expression of CD28 and CTLA-4 and laboratory parameters like white blood cells and platelets counts, and hemoglobin and lactate dehydrogenase level in AML patients. CD28 and CTLA-4 molecules are aberrantly expressed in peripheral blood leukocytes of AML patients and might contribute to the development of aGVHD after hematopoietic stem cell transplantation.

Liver transplant recipients are treated with various drugs, the metabolism of which is dependent on the cytochrome P450 polymorphic genotype. To identify the polymorphic variety of CYP2C19 genotype in liver allograft before and after transplantation. The study was conducted on 88 liver recipients. The CYP2C19 genotypes in donors and recipients were the same in 32 and different in 56 recipients. Extracted genomic DNA from the leukocytes and liver graft tissues were analyzed by TaqMan SNP genotyping assay. The distributions of homozygote, heterozygote, poor and ultra-rapid metabolizers’ genotypes were investigated in both groups. The distributions of CYP2C19 genotypes before transplantation in the blood and liver graft were within the normal range. After transplantation, in patients with different CYP2C19 genotype in donors and recipients, the genotypes of homozygote and ultra-rapid metabolizers were significantly decreased (p=0.024); the heterozygotes and poor metabolizer genotypes were significantly increased (p=0.017). The variety in CYP2C19 genotyping must be considered in patients with different genotypes in donor and recipients to predict the dosage regimens, optimize the treatment and decrease toxicity.