Donor-specific antibodies, glomerulitis, and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts.

BACKGROUND: The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation. METHODS: This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses. RESULTS: In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (P < 0.001), glomerulitis (P < 0.001), peritubular capillaritis (P < 0.001), and human leukocyte antigen (HLA) B eplet MM (P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy. CONCLUSIONS: PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.

[Clinicopathological analysis and differential diagnosis of primary peritoneal adenocarcinoma].

OBJECTIVE: To investigate the clinicopathological characteristics and differential diagnosis of primary peritoneal adenocarcinoma. METHODS: The clinico-pathological data of 8 patients with primary peritoneal adenocarcinoma, all female, aged 55.7 (45 - 69), were analyzed retrospectively. Immunohistochemistry was used to detect the expression of pan-cytokine, cytokine (CK) 7, CK20, CA125, CEA, epithelial membrane antigen (EMA), vimentin, calretinin, and P63 in the specimens of tumor obtained during tumor reduction surgery. Microscopy was conducted for pathological examination. RESULTS: The common clinical symptoms of these 8 patients included abdominal distention and ascites. Pre-operationally, 6 cases were diagnosed as with ovarian cancer, I case as with malignant mesothelioma, and I as with peritoneal carcinoma. The misdiagnosis rate was 87.5%. Post-operational pathological examination showed 7 cases of serous papillary adenocarcinoma and one case of mucinous adenocarcinoma. Immunohistochemistry showed the positive rates of the different biological markers as follows: pan-CK (8/8), CK7 (8/8), CK20 (1/8), CA125 (7/8), CEA (7/8), EMA (8/8), vimentin (1/8), calretinin (1/8), and P53 (8/8). CONCLUSION: A rare malignant tumor arising from the secondary Müllerian system, primary peritoneal adenocarcinoma shares similar histopathological characters with ovary carcinoma, so is easy to be misdiagnosed. Immunohistochemical staining is helpful to the differential diagnosis.

Specific suppression of beta-secretase gene expression by short interfering RNA in SK-N-SH cells.

OBJECTIVE: To test the effect of short interfering RNAs (siRNAs) of beta-site APP cleaving enzyme (BACE) on inhibiting the expression of BACE in mammalian cells. METHODS: The gene of EGFP, U6 promoter and beta-secretase targeting siRNA were cloned by PCR. The PCR products were inserted into the retrovirus plasmid pLXSN. The interfering vector was identified as pLXSN/ EGFP-U6-siBACE. The SK-N-SH cell line was produced, which can highly expressed BACE. The inhibitive effect of BACE siRNA on BACE expression was examined by fluoroscopy and immunohistochemistry tests. RESULTS: The interfering vector, pLXSN/EGFP-U6-siBACE, was constructed successfully. The BACE siRNA inhibited the expression of BACE in the SK-N-SH cell and reduced the production of Abeta. CONCLUSION: BACE siRNA inhibits the expression of BACE gene of mammalian, which has implications for RNA interference of Alzheimer's disease.