Juan Jin

Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection

Abstract Background: Endothelial cell antigens are important targets in acute rejection (AR). Our goal was to measure the serum concentrations of pre-transplant anti-endothelial cell antibody (AECA) in panel reactive antibody (PRA) negative recipients and its impact on AR within 6 months following renal transplantation. Methods: We retrospectively examined pre-transplant sera from 392 patients using cellular enzyme linked immunosorbent assay (ELISA) with substrate from a permanent endothelial cell line EAhy926. Equal volumes of serum from 40 healthy volunteers were mixed and used as the negative control. Results: The positive rate of AECA was 15.8%. There were no significant differences with respect to age, gender, original disease, dialysis history, immune suppressive regimen, cytomegalovirus (CMV) antigen positive rate, complement dependent cytotoxicity (CDC) level and soluble CD30 (sCD30) levels between the AECA positive group and AECA negative group. AR rate in the AECA positive group was higher than that in the AECA negative group (35.5% vs. 22.4%, p=0.023). The AECA positive patients had significantly higher rates of acute grade II T-cell mediated rejection (TMR) and acute antibody mediated rejection (AMR) compared with AECA negative patients. The concentrations of sCD30, and AECA were independent risk factors for AR within 6 months; the odds ratios were 7.005 and 2.469, respectively. Conclusions: Positive AECA was an independent risk factor for AR and appeared to correlate with relatively severe rejection subtypes. Clin Chem Lab Med 2009;47:1265–9.

The regulatory/cytotoxic infiltrating T cells in early renal surveillance biopsies predicts acute rejection and survival

BACKGROUND To analyze the immune phenotype of T-lymphocyte infiltrations in surveillance renal biopsies with stable renal function early post-transplantation (median time 40 days, range from 18 to 85 days). METHODS One hundred and twenty-five surveillance biopsies with interstitial T-lymphocyte infiltration between non-atrophic tubules in the cortex (14 with subclinical rejection, 32 with borderline change and 79 with only interstitial T-lymphocyte infiltration but no obvious pathological abnormalities according to Banff criteria) were enrolled. All cases were classified into two groups: regulatory phenotype (RP) group, which was dominated by FOXP3-positive T lymphocytes in surveillance biopsies, and cytotoxic phenotype (CP) group, which was dominated by Granzyme B-positive T lymphocytes. RESULTS The RP group includes 83.2% (104/125) cases, none of which developed acute rejection during nearly 5 years of follow-up. The CP group includes 16.8% (21/125) cases, all of which developed biopsy-proven acute rejection or clinical diagnostic acute rejection within 1 year after biopsy. Glomerular filtration rate and cumulative graft survival time were superior in the RP group than in the CP group (P<0.001). CONCLUSION Analyzing the immunophenotype of graft-infiltrating T cells in renal surveillance biopsies during early post-transplantation could predict acute rejection and survival.

Protective effect of indomethacin in renal ischemia-reperfusion injury in mice *

ObjectiveTo evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs (NSAIDs) in renal ischemia-reperfusion injury (IRI) and the cyclooxygenase (COX)-1/2 blockade association by indomethacin (IMT) in the mice model.MethodsAfter the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses: 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine (SCr) using enzyme-linked immunosorbent assay (ELISA) kits. Kidney samples were analyzed by hematoxylin and eosin (H&E) and immunohistochemistry stainings. Results: The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage. The tumor necrosis factor α (TNF-α) activity in renal homogenates and interleukin 6 (IL-6) activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups.ConclusionsThere was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.概要研究目的在小鼠模型中利用吲哚美辛阻断COX-1/2 通路, 探讨非甾体类抗炎药对肾缺血再灌注损伤的保护作用。创新要点非甾体类抗炎药被认为具有肾毒性, 本研究首次在小鼠模型中探讨非甾体类抗炎药对肾缺血再灌注损伤的保护作用。研究方法小鼠左侧肾蒂夹闭后, 通过腹腔注射不同剂量的吲哚美辛, 在肾缺血再灌注损伤24 小时后, 获取血液和肾脏标本。 利用酶联免疫 (ELISA) 试剂盒测定血清肌酐和细胞因子浓度来评估肾功能, 肾组织样本进行苏木精-伊红染色和免疫组化分析。重要结论腹腔注射吲哚美辛5 mg/kg 组的小鼠血清肌酐值与对照组相比显著降低, 肾小管损伤也显著减轻 (见图1 和2); 腹腔注射5 和7 mg/kg 吲哚美辛组的小鼠血清肾肿瘤坏死因子-α 和白介素-6 的浓度显著降低 (见图3a 和3b); 腹腔注射3 和5 mg/kg 吲哚美辛组的小鼠血清血栓素B2 与 6-酮前列腺素 F1α 的比值明显降低 (见图3c); 腹腔注射 5 mg/kg 吲哚美辛组小鼠肾组织 COX-1 和 COX-2 染色较弱 (见图4)。 因此, 吲哚美辛对小鼠肾缺血再灌注损伤的作用与其剂量相关, 在某个特定的剂量范围内具有肾保护作用。 吲哚美辛对小鼠肾缺血再灌注损伤的保护作用与阻断 COX-1/2 有关。

Proteins induced by telomere dysfunction are associated with human IgA nephropathy

Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers (cathelin-related antimicrobial peptide (CRAMP), stathmin, elongation factor-1α (EF-1α), and chitinase) were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy (IgAN) progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus (SLE), diabetic nephropathy (DN), and focal segmental glomerulosclerosis (FSGS), there is no protein upregulation with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% (plasma) and 74.3%/84.2% (urine) sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.

Peritubular Capillaritis in Early Renal Allograft Dysfunction Is an Indicator of Acute Rejection

BACKGROUND Kidneys showing acute rejection (AR) processes often are accompanied by various levels of peritubular capillaritis (Ptc), especially cases of acute humoral rejection (AHR). However, it is not known whether the presence of Ptc alone is sufficient evidence of allograft rejection. This study was performed to determine the diagnostic value of Ptc as a marker for AR among cases of early renal allograft dysfunction. METHODS Fifty-three AR showed C4d deposition in the peritubular capillaries (PTCs; C4d+AR group), 50 AR were without C4d deposition (C4d-AR group), 30 had Ptc alone (Ptc group), 28 had acute tubular necrosis (ATN group), and 78 were surveillance biopsies (control group). RESULTS Analyzing the immunophenotype of infiltrating T lymphocytes and serum antibodies, discovered that 85.9% of control biopsies presented with a regulatory phenotype. Among the Ptc cohort, 93.3% of biopsies showed the cytotoxic phenotype with no significant different between C4d+AR and C4d-AR (96.2% vs 92.0%). We also observed the prevalence of panel-reactive antibody (PRA) and major-histocompatibility-complex class I chain-related gene A (MICA) antibodies to be increased among Ptc (30.0% and 43.3%, respectively), albeit not significantly different from C4d+AR (49.1% and 39.6%, respectively). The prevalences were low in other groups. CONCLUSIONS These results implied that Ptc in biopsy specimens from patients with early renal allograft dysfunction was an indicator of AR, especially AHR.

Effects of chimerism on the mice heart transplanted survival with the bone marrow infusion.

AIMS To evaluate the effects of chimerism on the mice heart transplanted survival with the bone marrow infusion. METHODS Bone marrow cells (BMCs) were obtained from BALB/c mice. These BMCs were injected into the irradiated (2Gy-Co60) C57BL/6 mice through femoral vein. Then Group A mice were treated with Cyclosporine (1mg/kg) for 21days and Group B were not treated with Cyclosporine. Group C were treated as the control group without BMCs infusion. Group D were treated with Cyclosporine (1mg/kg) for 21days pre-hearttransplantation without BMCs infusion. After 21days, the C57BL/6 mice received heart allografts from BALB/c. To determine the degree of chimerism in BMCs infusion recipients, peripheral blood were isolated on day 7, 14, 21. Allografts were harvested 10days after heart transplantation for the histological analysis. RESULTS (1) Chimerism detected in the peripheral blood of Group A mice on day 7 after BMCs infusion was 6.1±2.5%, on day 14 was 15.4±2.9% and on day 21 was 10.7±2.6%. For the Group B mice on day 7 after BMCs infusion, the chimerism was 2.8±1.1%, on day 14 was 11.2±4.8% and on day 21 was 7.4±3.7%. For the Groups C and D mice, no chimerism was observed. Group A mice had the tendency toward improved level of chimerism than Group B mice. (2) The survival time of Group A (n=6) was 13.0±1.4days which was significantly longer than Group B (n=6) with the survival time was 8.5±1.3days (p<0.001), also longer than the mice in Groups C and D, the survival time of which were 10.0±1.3days (p=0.008) and 9.4±1.1days (p=0.004). There is no significant difference among Groups B, C, and D. (3) The HE staining showed the much more seriously heart rejection in Groups B, C and D than Group A. CONCLUSIONS The chimerism was found in the BMCs infusion groups. Without the CsA treatment combined with chimerism could not protect the transplanted heart. There was no obvious evidence showed that the chimerism alone could improve the survival time of cardiac allografts in mice.

Effects of chlorpyrifos exposure on kidney Notch2-Jagged1 pathway of early prenatal embryo.

AIMS To evaluate the effects of this insecticide on the embryonic development of kidney and to assess the important role of Notch2-Jagged1 pathway in this duration. METHODS AND RESULTS Chlorpyrifos (CPF) 5 mg/kg/d were administrated on gestation 7.5-11.5 day by subcutaneous injection. On gestation 16.5 day, the normal embryo kidney developed through S shape duration to the original kidney, which had the nephrons and could start to secret the urine. But for the CPF-treated mice, the embryo kidney developed much more slowly, they did not show the S shape and the nephrons. The Notch2-Jagged1 pathway should be expressed stronger in the normal embryo kidney on gestation 16.5 day, but for the CPF-treated mice we found the obvious weak pathway staining. CONCLUSIONS CPF broke the Notch2-Jagged1 pathway during the embryo kidney development, and the Notch2-Jagged1 pathway plays an important role in the S shape to original kidney formation duration.

Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes

Aggressive NK-cell leukemia (ANKL) is a rare form of NK cell neoplasm sporadically affecting people from Asia and Central and South America. The median overall survival (OS) is less than 2 months, irrespective of treatments. Epstein-Barr virus (EBV) is mostly detected in the leukemia cells and is proposed to contribute to the pathogenesis of ANKL. ANKL represents a distinct disease entity within the continuous spectrum of EBV-associated T/NK-cell lymphoproliferative diseases (EBV-T/NKLPDs). Patients with ANKL usually manifest a fulminant and extremely aggressive clinical course. However, some clinicopathologic features may be shared with different types of EBV-T/NK-LPDs, which leads to the occurrence of a few cases with features intermediate between two similar disorders. The diagnosis of ANKL largely relies on the identification of morphologically and immunophenotypically aberrant leukemia cells. Chromosomal gains and losses, activating STAT3 and STAT5 mutations, and HACE1 hypermethylation have only been sporadically detected. Moreover, optimal therapy of ANKL has not yet been established. To date, less than 350 cases of ANKL have been described in English literature worldwide. Because of the rarity of ANKL, the clinical features, potential pathogenesis, therapeutic strategies, and prognostic factors still lack in understanding. A multicenter study is critically needed for better understanding of this disease. Here we conducted a 13-year retrospective study with 113 confirmed ANKL patients enrolled in 10 clinical centers located in different geographic regions across China. All cases were centrally reviewed by three hematopathologists and three hematologists. Study design, enrolled clinical centers, and data collection were described in the Supplementary Methods. This study was approved by the institutional review board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Informed consent was obtained from each individual in accordance with the principles expressed in the Declaration of Helsinki. From October 2003 to July 2016, a total of 161 suspected cases were collected, and 113 cases with eligibility consensuses after central review were finally enrolled. All the patients were of the Han nationality living in the mainland China and had no history of chronic active EBV disease (CAEBV), severe mosquito bite allergy, hydroa vacciniforme, or other T/NK-LPDs. Patient eligibility and general characteristics, including immunophenotyping and EBV detection of leukemia cells, were summarized in Supplementary Results and Supplementary Tables S1 and S2. The distribution of onset age was illustrated in Supplementary Fig. S1A showing an incidence peak in patients between 21 and 30 years old (29.20%, 33/113), with a male to female ratio of nearly 2:1 in this decade. The median OS was only 55 days (Supplementary Tables S2) and 1-year survival rate was only 4.42% (5/113; Supplementary Fig. S1B), which indicated a dismal outcome of ANKL.

A Giant Facial Nerve Schwannoma Extending from the Middle Cranial Fossa to the Mastoid Region: Case Report

Facial nerve schwannomas are uncommon benign tumours and seldom extend into the middle cranial fossa. This is a case report of a giant facial nerve schwannoma extending from the middle cranial fossa to the mastoid region, which was successfully removed using combined interdisciplinary subtemporal and transmastoid approaches. Complete resection of the tumour was the optimal therapy for this patient because the facial nerve had been severely destroyed by the tumour. The clinical presentation, histological features, radiological findings and management of this case, as well as the relevant literature, are presented.