Hyporesponsiveness against donor's ABO antigens of renal grafts after ABO-incompatible kidney transplantation.

BACKGROUND: ABO antigens expressed on the red blood cells (RBCs) are not identical to those expressed on the renal endothelial cells. The isohemagglutinin assay employing the RBCs is the gold standard for evaluating anti-ABO antibody (Ab) levels. However, it remains unclear whether the anti-ABO Abs detected by the isohemagglutinin assay after ABO-incompatible (ABOi) kidney transplantations (KTx) that are not associated with antibody-mediated rejection can bind to renal graft endothelial cells. METHODS: Ninety plasma samples were collected from patients with stable graft function after ABO-compatible (ABOc) or ABOi KTx. Anti-ABO Ab titers were examined by both the isohemagglutinin assay and the CD31-ABO microarray, which was developed as a mimic of the ABO antigens expressed on the renal endothelial cells. RESULTS: The antibody titers detected by the isohemagglutinin assay and the CD31-ABO microarray after the ABOc KTx relatively correlated with each other. However, the CD31-ABO microarray results showed low antibody levels against donor blood group antigens after ABOi KTx and did not correlate with the isohemagglutinin assay. In contrast, the antibody levels against non-donor blood group antigens after ABOi KTx were comparable to those after the ABOc KTx. Fourteen patients received graft biopsies, and no antibody-mediated rejection was observed in ABOi KTx recipients, except for two patients who had anti-donor-HLA Abs. CONCLUSION: The present study suggested that the anti-ABO Abs detected by the isohemagglutinin assay after ABOi KTx with stable graft function were hyporeactive to the ABO antigen of graft renal endothelial cells.

A Novel Method of CD31-Combined ABO Carbohydrate Antigen Microarray Predicts Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

Isohemagglutinin assays employing red blood cells (RBCs) are the most common assays used to measure antibody titer in ABO-incompatible kidney transplantation (ABOi KTx). However, ABO antigens expressed on RBCs are not identical to those of kidney and antibody titers do not always correlate with clinical outcome. We previously reported that CD31 was the main protein linked to ABO antigens on kidney endothelial cells (KECs), which was different from those on RBCs. We developed a new method to measure antibody titer using a microarray of recombinant CD31 (rCD31) linked to ABO antigens (CD31-ABO microarray). Mass spectrometry analysis suggested that rCD31 and native CD31 purified from human kidney had similar ABO glycan. To confirm clinical use of CD31-ABO microarray, a total of 252 plasma samples including volunteers, hemodialysis patients, and transplant recipients were examined. In transplant recipients, any initial IgG or IgM antibody intensity >30,000 against the donor blood type in the CD31-ABO microarray showed higher sensitivity, specificity, positive predictive value, and negative predictive value of AABMR, compared to isohemagglutinin assays. Use of a CD31-ABO microarray to determine antibody titer specifically against ABO antigens expressed on KECs will contribute to precisely predicting AABMR or preventing over immunosuppression following ABOi KTx.

Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis.

BACKGROUND: We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. METHODS: We selected 394 individuals (169 males and 225 females) who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. RESULTS: The multivariate-adjusted model showed that age (odds ratio (OR), 1.034; 95% confidence interval (95%CI), 1.010 - 1.059), HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225), and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051) were significant variables that could independently predict the risk of new carotid artery atherosclerosis. CONCLUSION: The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis.

Sleep duration is significantly associated with carotid artery atherosclerosis incidence in a Japanese population.

BACKGROUND: Previous studies have indicated that sleep duration is associated with total mortality in a U-shaped fashion. The purpose of the current study was to examine the relationship between self-reported sleep duration and carotid artery atherosclerosis in a Japanese population. METHODS: In 2009-2010, a total of 2498 participants (1195 men, 1303 women; age range, 23-92 years) were recruited from members of a Japanese community receiving annual health check-up at a local health center who agreed to participate in the study. Exclusion criteria were as follows: age <40 or ≥85 years; and more than one missing value from either laboratory data or questionnaire responses. A total of 2214 participants were entered into the study. Carotid artery arteriosclerosis was evaluated ultrasonographically and quantified as intima-medial thickness (IMT). The presence of carotid artery atherosclerosis was defined as IMT≥1.2 mm. Sleep durations were compared with IMT measurements after controlling for confounding factors such as age, sex, lipid profile, fasting plasma glucose, hemoglobin A1c, blood pressure, alcohol intake, and smoking habit. RESULTS: Sleep duration ≥7 h correlated significantly with the incidence of IMT≥1.2 m when compared with a sleep duration of 6 h (multivariate-adjusted odds ratio, 1.263; 95% confidence interval, 1.031-1.546, P=0.024). Shorter sleep duration ≤5 h did not correlate significantly with the risk compared with a sleep duration of 6 h. CONCLUSION: Long sleep duration (≥7 h) correlated significantly with the incidence of carotid artery atherosclerosis compared with a sleep duration of 6 h, but shorter sleep duration did not.

[Results of antifungal susceptibility testing of Candida species and trends of antifungal use in Niigata university medical and dental hospital].

The accuracy of antifungal susceptibility testing is important for the clinical management of patients with serious infections due to fungus. Our primary objective was to analyze the results of antifungal susceptibility testing of Candida species performed at Niigata University Medical and Dental Hospital and usage of antifungal agents. Antifungal susceptibility testing was performed by the CLSI M27-A2 method. Yeast-like fungi were isolated from 6% of 6,730 samples. All isolates were Candida species, i.e., C. albicans (50%), C. parapsilosis (28%), C. guilliermondii (9%), C. krusei (5%), C. glabrata (4%), and C. tropicalis (4%). The results of the minimum inhibitory concentration that inhibits 90% of the strain tested (MIC90) were 1 microg/mL for fluconazole, 0.5 microg/mL for miconazole, 0.06 microg/mL for itoraconazole, < or = 0.03 microg/mL for micafungin, respectively. The results of non-albicans species were 32 microg/mL for fluconazole, 8 microg/mL for miconazole, 0.5 microg/mL for itoraconazole, 1 microg/mL for micafungin, respectively. All Candida species were susceptible to the available antifungal agents, except C. krusei that was resistant to fluconazole. Thus, antifungal susceptibility varies greatly according to fungal species. The accuracy of identification of the fungus and antifungal susceptibility would contribute to the proper management of patients with serious fungal infections.

[Report on a training course for clinical research coordinators].

Recently, nurses and pharmacists have become to play important roles in clinical trials as clinical research coordinators (CRC). However, clinical laboratory personnel have a very few chances to contribute to such tasks. CRCs have responsibility to protect the human rights, to assure the safety of volunteers during studies, and to keep quality of data. One of the authors had a chance to participate in a training course for CRC that was held in Tokyo, 2004. In this paper, we report about the training course and roles of CRC. We also discuss how laboratory personnel should contribute to clinical trials.