Novel susceptibility alleles in HLA region for myositis and myositis specific autoantibodies in Korean patients.

OBJECTIVES: HLA genes are a major genetic risk factor for myositis and myositis specific antibodies (MSAs), exhibiting unique HLA backgrounds for myositis in different ethnic groups. This is the first large scale Korean study to genotype the HLA-DRB1 and -DPB1 alleles and to examine their association with myositis and MSAs. METHODS: HLA-DRB1 and HLA-DPB1 alleles and MSAs were examined in 179 patients with dermatomyositis (DM, n = 129) or polymyositis (PM, n = 50) and healthy controls (n = 800 for HLA-DRB1, n = 548 for HLA-DPB1). Associations between individual HLA alleles and myositis/MSA were examined. Bonferroni correction was applied for multiple testing comparing patients and controls. RESULTS: A total of 33 HLA-DRB1 and 24 HLA-DPB1 alleles were genotyped in patients and controls. MSAs were found in 67.0% of patients. Anti-MDA5 (26.8%) and anti-aminoacyl-tRNA synthetase antibodies (15.6%) were most common, followed by anti-Mi2 (9.5%) and anti-TIF1γ antibodies (8.9%). HLA-DRB1*12:02 and HLA-DRB1*14:03 were associated with DM and PM, respectively. HLA-DRB1*12:02 was associated with anti-MDA5, HLA-DRB1*08:03 with anti-ARS, HLA-DRB1*14:03 with anti-SRP, and HLA-DRB1*07:01 with anti-Mi2 antibodies. Although HLA-DRB1*13:01 was associated with anti-TIF1γ antibodies, the frequency of HLA-DRB1*13:01 was rare. HLA-DPB1*02:01 was negatively associated with myositis and PM while HLA-DPB1*17:01 was associated with anti-Mi2 positive DM. CONCLUSIONS: Unique immunogenetic background was observed for Korean patients with myositis. Novel myositis susceptibility alleles, HLA-DRB1*12:02 and HLA-DRB1*14:03, were identified, together with MSA-associated HLA alleles unique to Korean patients with myositis.

Pretransplantation fetal-maternal microchimerism in pediatric liver transplantation from mother.

AIM: To investigate the rates of pretransplantation fetal-maternal microchimerism (MC) and its effect on rejection in children receiving maternal liver grafts. METHODS: DNA or blood samples before liver transplantation (LT) were available in 45 pediatric patients and their mothers. The presence of pretransplantation MC to non-inherited maternal antigens (NIMAs) (NIMA-MC) in the peripheral blood was tested using nested PCR-single-strand conformation polymorphism analysis for the human leukocyte antigen (HLA)-DRB1 alleles. NIMA-MC was successfully evaluated in 26 of the 45 children. Among these 45 pediatric LT recipients, 23 children (51.1%) received transplants from maternal donors and the other 22 from non-maternal donors. RESULTS: Among these 26 children, pretransplantation NIMA-MC was detected in 23.1% (n = 6), 6.1 (range, 0.8-14) years after birth. Among the children with a maternal donor, the rate of biopsy-proven cellular rejection (BPCR) was 0% in patients with NIMA-MC positivity (0/3) and those with HLA-DR identity with the mother (0/4), but it was 50% in those with NIMA-MC negativity (5/10). Patients with NIMA-MC positivity or HLA-DR identity with the mother showed significantly lower BPCR rate compared with NIMA-MC-negative patients (0% vs 50%, P = 0.04). NIMA-MC-positive patients tended to show lower BPCR rate compared with NIMA-MC-negative patients (P = 0.23). CONCLUSION: The presence of pretransplantation NIMA-MC or HLA-DR identity with the mother could be associated with BPCR-free survival in pediatric recipients of LT from maternal donors.

Frequency of fetal-maternal microchimerism: an analysis of the HLA-DRB1 gene in cord blood and maternal sample pairs.

PURPOSE: We aimed to investigate the frequency of fetal-maternal microchimerism among cord blood (CB) from a Korean population. MATERIALS AND METHODS: We previously developed a nested polymerase chain reaction-single-strand conformation polymorphism method for microchimerism detection that is highly sensitive (0.01-0.001%) and specific. We used this method to investigate the frequency of fetal-maternal HLA-DRB1 microchimerism among 153 maternal and 152 CB samples. RESULTS: Among the tested pairs, 41.1% exhibited at least one direction of microchimerism, 32.0% of the mothers possessed fetal microchimerism, and 23.4% of the newborns possessed maternal microchimerism. The overall microchimerism frequency was 28.2%. CONCLUSIONS: We hypothesize that the different microchimerism frequencies among population and methods are due to differences in detection specificities and subject characteristics. This study provides basic data on fetal-maternal microchimerism that may be useful for future studies on autoimmune disorder and virtual phenotyping in transplantation.

Association of human leukocyte antigen with postherpetic neuralgia in Koreans.

Postherpetic neuralgia (PHN), the most frequent complication of varicella-zoster virus reactivation, is characterized by pain that persists for more than 3 months, often for years after healing of zoster rash. A few studies revealing the association of human leukocyte antigen (HLA) with PHN have been reported, but only in the Japanese. The aim of this study was to investigate the primary HLA locus associated with PHN susceptibility in Koreans. We compared HLA-A, -B, -C, and DRB1 genotypes of 66 PHN patients with those of 54 herpes zoster (HZ) patients without developing PHN and 235 healthy controls. Frequencies of HLA-B*13, B*44, B*15 (B75), DRB1*10:01, and DRB1*12:02 were increased, and those of HLA-C*01, C*12, and DRB1*01:01 were decreased in PHN patients compared to those in controls (each, p < 0.05). Among these alleles, only the frequency of HLA-B*44 was significantly increased in PHN patients compared to that in HZ patients and the change was due to HLA-B*44:03 (PHN vs controls, p = 0.043; PHN vs HZ, p = 0.012). The results suggest that HLA-B*44:03 or other closely linked gene of the major histocompatibility complex is associated with susceptibility to the development of PHN after HZ, but not with the onset of HZ.

HLA-C*01 is a Risk Factor for Crohn's Disease.

BACKGROUND: A dysregulated mucosal immune response to the intestinal environment in a genetically susceptible host is hypothesized to be critical to the pathogenesis of Crohn's disease (CD). Therefore, we examined CD-susceptibility genes involved in the immune response through a genome-wide association study and consecutive genotyping of human leukocyte antigens (HLAs) and killer cell immunoglobulin-like receptors. METHODS: An initial genome-wide association study was performed with 275 CD patients and 2369 controls from a Korean population. To validate the loci identified in the genome-wide association study, replication genotyping was performed in a different cohort of 242 CD patients and 1066 controls. Finally, high-resolution genotyping of HLA and killer cell immunoglobulin-like receptor was performed. RESULTS: Four susceptibility loci, a promoter region in tumor necrosis factor (ligand) superfamily member (TNFSF15) and 3 independent regions in HLAs, showed significant associations with CD. Among them, rs114985235 in the intergenic region between HLA-B and HLA-C showed the strongest association, with an increased risk of CD (P = 8.71 × 10; odds ratio, 2.25). HLA typing in this region showed HLA-C*01 to be responsible for the association of CD among 43 HLA-B and HLA-C genotypes identified in the Korean population. However, the interaction of HLA-C with killer cell immunoglobulin-like receptor had little effect on the development of CD. CONCLUSIONS: We newly identified HLA-C*01 as a prominent CD-susceptibility HLA allotype in the Korean population. In addition, these results confirm that genetic variations in immune response genes, such as HLAs and TNFSF15, are important host factors for the pathogenesis of CD.

Effect of major histocompatibility complex haplotype matching by C4 and MICA genotyping on acute graft versus host disease in unrelated hematopoietic stem cell transplantation.

We explored whether matching of human leukocyte antigen (HLA) haplotypes between the recipient and donor of hematopoietic stem cell transplantation (HSCT) predicted by C4 and MICA typing is associated with the incidence of acute graft versus host disease (aGVHD). DNA preparations collected from a total of 81 recipient and donor pairs were used for PCR-based C4 subtyping and/or MICA sequence-based typing. Incidences of aGVHD were compared according to C4 and MICA matching. The six most common MICA alleles were MICA*008:01, *010:01, *002:01, *004, *009:01/049, and *012:01. Among the 59 unrelated pairs, HLA alleles were matched in 34 (57.6%). C4 subtypes were identical between the recipient and donor in 28 (82.4%) HLA-matched unrelated pairs, while MICA genotypes were matched in all HLA-matched unrelated pairs. In the 22 HLA-matched related pairs, all recipients showed identical C4 subtypes with their respective donors. In multivariate analysis, C4 mismatch was a significant risk factor associated with the development of aGVHD in unrelated HSCT (hazard ratio=3.24, P=0.006). PCR-based C4 subtyping is a simple method for assessing the genetic identity of the HLA region between a recipient and unrelated donor. This test would be also useful for prediction of aGVHD in HSCT.

A Family with Axenfeld-Rieger Syndrome: Report of the Clinical and Genetic Findings.

PURPOSE: To describe clinical findings in a Korean family with Axenfeld-Rieger syndrome. METHODS: A retrospective review of clinical data about patients with diagnosed Axenfeld-Rieger syndrome. Five affected members of the family underwent a complete ophthalmologic examination. We screened the forkhead box C1 gene and the pituitary homeobox 2 gene in patients. Peripheral blood leukocytes and buccal mucosal epithelial cells were obtained from seven members of a family with Axenfeld-Rieger syndrome. DNA was extracted and amplified by polymerase chain reaction, followed by direct sequencing. RESULTS: The affected members showed iris hypoplasia, iridocorneal adhesions, posterior embryotoxon, and advanced glaucoma in three generation. None had systemic anomalies. Two mutations including c.1362_1364insCGG and c.1142_1144insGGC were identified in forkhead box C1 in four affected family members. CONCLUSIONS: This study may help to understand clinical findings and prognosis for patients with Axenfeld-Rieger syndrome.

Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis in Koreans.

Tuberculosis remains an important public health problem in Koreans. However, very few studies have reported on the genetic factors associated with TB susceptibility in Koreans. The aim of this study was to elucidate the genetic factors associated with susceptibility to pulmonary tuberculosis (PTB). We investigated the transporter associated with antigen processing -1 (TAP1) and TAP2 gene polymorphisms in 160 Korean PTB patients (categorized according to extent of lesion and TB medication history) and 210 controls. TAP2*C/E frequency was significantly increased in the PTB (pc = 0.004, OR = 2.28). TAP2*Bky2/C/E were enriched in the retreated, far-advanced and total PTB compared with the controls (pc = 0.015, OR = 3.27; pc = 0.019, OR = 2.56; pc = 2.8 × 10(-4) , OR = 2.42, respectively). In the comparison of TAP2 gene with the DRB1*08:03, which is associated with TAP2*Bky2 and PTB in Koreans, we demonstrated the hierarchy of these association factors. TAP2*C/E is independent factors as strong as DRB1*08:03, and TAP2*C/E interacts with DRB1*08:03, resulting in a striking combined association. Our results suggest that TAP2 gene has an association with PTB susceptibility, the extent of the lesion or recurrence. These associations are independent from and additive with DRB1*08:03.

Spectral domain optical coherence tomography cross-sectional image of optic nerve head during intraocular pressure elevation.

AIM: To analyze changes of the optic nerve head (ONH) and peripapillary region during intraocular pressure (IOP) elevation in patients using spectral domain optical coherence tomography (SD-OCT). METHODS: Both an optic disc 200×200 cube scan and a high-definition 5-line raster scan were obtained from open angle glaucoma patients presented with monocular elevation of IOP (≥30 mm Hg) using SD-OCT. Additional baseline characteristics included age, gender, diagnosis, best-corrected visual acuity, refractive error, findings of slit lamp biomicroscopy, findings of dilated stereoscopic examination of the ONH and fundus, IOP, pachymetry findings, and the results of visual field. RESULTS: The 24 patients were selected and divided into two groups: group 1 patients had no history of IOP elevation or glaucoma (n=14), and group 2 patients did have history of IOP elevation or glaucoma (n=10). In each patient, the study eye with elevated IOP was classified into group H (high), and the fellow eye was classified into group L (low). The mean deviation (MD) differed significantly between groups H and L when all eyes were considered (P=0.047) and in group 2 (P=0.042), not in group 1 (P=0.893). Retinal nerve fiber layer (RNFL) average thickness (P=0.050), rim area (P=0.015), vertical cup/disc ratio (P=0.011), cup volume (P=0.028), inferior quadrant RNFL thickness (P=0.017), and clock-hour (1, 5, and 6) RNFL thicknesses (P=0.050, 0.012, and 0.018, respectively), cup depth (P=0.008), central prelaminar layer thickness (P=0.023), mid-inferior prelaminar layer thickness (P=0.023), and nasal retinal slope (P=0.034) were significantly different between the eyes with groups H and L. CONCLUSION: RNFL average thickness, rim area, vertical cup/disc ratio, cup volume, inferior quadrant RNFL thickness, and clock-hour (1, 5, and 6) RNFL thicknesses significantly changed during acute IOP elevation.

Effectiveness of the ICare rebound tonometer in patients with overestimated intraocular pressure due to tight orbit syndrome.

PURPOSE: To evaluate the effectiveness of the ICare rebound tonometer in patients with overestimated intraocular pressure (IOP) due to tight orbit syndrome and to identify factors affecting the development of tight orbit syndrome in glaucoma patients. METHODS: We investigated 84 eyes in 84 glaucoma patients, of which 14 eyes were classified in the tight orbit syndrome group and 70 eyes in the control group. IOP was measured using the ICare tonometer and the Goldmann applanation tonometer (GAT). The demographic data, medical histories, ocular histories, and detailed ocular drug histories of the two groups were compared to identify factors contributing to the development of tight orbit syndrome. RESULTS: In the tight orbit syndrome group, the ICare tonometer significantly underestimated the IOP by approximately 8.6 mmHg compared with the GAT. In the control group, the IOP readings of the GAT and the ICare tonometer did not differ significantly. Bland-Altman analysis showed that the mean difference between measurements taken using the GAT and those taken using the ICare tonometer was 2.5 ± 6.3 mmHg. The difference between the GAT and ICare tonometer measurements was greater in the tight orbit syndrome group (8.6 ± 5.3 mmHg) than in the control group (1.3 ± 2.7 mmHg). Multivariate regression analysis revealed that only the use of prostaglandin analogs (PGAs) was associated with the development of tight orbit syndrome. CONCLUSIONS: The ICare tonometer is a suitable alternative device for use in patients with tight orbit syndrome in whom the IOP may be overestimated with the GAT. The prolonged use of PGAs is significantly associated with the development of tight orbit syndrome.

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

The minimum number of cord blood units needed for Koreans is 51,000.

BACKGROUND: The inventory size for cord blood (CB) depends on the ethnic diversity of human leukocyte antigen (HLA) and the size estimation is important for public health in each ethnicity. STUDY DESIGN AND METHODS: We estimate the CB inventory size in Koreans with stored CB units (CBUs) and patients who underwent allogeneic hematopoietic stem cell transplantation. Two-digit HLA specificities were determined using intermediate DNA typing. From 17,508 stored Korean CBUs, 1460 haplotypes with a frequency greater than 0.001% were used for reconstitution of the HLA. A total of 1002 transplanted patients' HLA was used for matching probability calculation. RESULTS: The best probability for 6/6 matching is 47% in 500,000 hypothetical size. Ninety-five percent probability is achieved with 51,000 CBUs in 5/6, and 2150 in 4/6 matching condition. Because 4/6 matched CB is rarely selected in the Korean situation, 51,000 units is the lowest limit of CBUs required and the number will be adjusted depending on the cell number required for patients and the resolution of HLA typing. CONCLUSION: Approximately 51,000 units could provide the minimum requirement for hematopoietic transplantation in Korea.

Irradiated and activated autologous PBMCs induce expansion of highly cytotoxic human NK cells in vitro.

Adoptive cell transfer of ex vivo-activated natural killer (NK) cells is a promising therapy for cancer treatment. Because of inhibitory signaling through killer immunoglobulin-like receptor (KIR)-KIR ligands, KIR-mismatched allogeneic NK cell transfer is considered to be a more effective strategy than is autologous transfer. However, purified NK cells do not expand well enough in vitro with good manufacturing practice-compliant components for clinical use. Some investigators have developed selective expansion of NK cells from peripheral blood mononuclear cells, but these cells have the risk of graft-versus-host disease in allogeneic settings because of T cells contamination. In this study, we developed a novel method for NK cell activation and expansion. Using only good manufacturing practice-compliant components and autologous feeder cells, once purified NK cells were effectively expanded (2500-fold at day 17). The expanded cells were highly purified NK cells, and the use of these cells is suitable for allogeneic transfer without the risk of graft-versus-host disease induction. Importantly, the expanded NK cells also showed enhanced cytotoxicity compared with NK cells conventionally expanded by recombinant human interleukin 2. Finally, induction of NKG2D ligand expression on feeder cells implies that the NKG2D-NKG2DL interaction may play a role in NK cell expansion. In conclusion, this method can be used to obtain NK cells for more successful allogeneic NK cell adoptive transfer for use in antitumor immune therapy.

Genetic and non-genetic factors affecting the visual outcome of ocular Behcet's disease.

OBJECTIVE: To examine the prognostic factors for visual outcome in Korean BD patients with uveitis. METHODS: Seventy-seven Korean BD patients with uveitis were enrolled. HLA-B and HLA-A genotypes were determined by PCR-based method. Visual acuity was measured by Snellen chart. Vision loss was graded into visual impairment (VI) defined as VA<20/40 for more than 6 months, loss of useful vision (LUV) as VA < 20/200, and near total blindness (NTB) as VA of light perception or worse. RESULTS: VI was associated with a longer duration of uveitis, posterior uveitis, and cataract, LUV with male gender, a longer duration of uveitis, posterior uveitis, and cataract, and NTB with a longer duration of uveitis, cataract, and glaucoma. HLA-B*51 and HLA-A*26:01 did not show any association with VI, LUV, or NTB. However, HLA-B*51 carriers had earlier onset of uveitis and HLA-A*26:01 was strongly associated with posterior uveitis. In patients with posterior uveitis, VI was associated with a longer duration of uveitis and cataract, LUV with a longer duration, and NTB with HLA-B*51. CONCLUSION: Longer duration of uveitis, posterior uveitis, male gender, cataract, and glaucoma were found to be associated with poor visual outcome in BD-related uveitis. HLA-B*51 was associated with NTB in patients with posterior uveitis. HLA-A*26:01 showed no association with VI, LUV, or NTB, however, was strongly associated with posterior uveitis.

Associations of HLA-DRB1 and -DQB1 alleles with severe recurrent respiratory papillomatosis in Korean patients.

Recurrent respiratory papillomatosis (RRP) is characterized by frequent recurrences of papilloma of the larynx with significant morbidity. It is caused by human papillomavirus (HPV) types 6 and 11. Some associations of HLA genes with RRP have been reported, mainly in Caucasians. We performed HLA class II (DRB1 and DQB1) genotyping using Dynal RELI™ HLA-DRB1 SSO kit and PCR-single strand conformation polymorphism on 22 Korean patients with severe RRP and 207 healthy controls. The gene frequencies of HLA-DRB1*11:01 (18.2% vs 3.6%, p=0.0006, pc=0.02, odds ratio [OR]=5.9) and DQB1*03:01 (36.4% vs 14.5%, p=0.0009, pc=0.01, OR=3.4) and the haplotype frequency of DRB1*11:01-DQB1*03:01 (15.9% vs 3.6%, p=0.003, OR=5.0) was higher in RRP patients than controls. DRB1*11:01 and DRB1*11:01-DQB1*03:01 haplotype were strongly associated with disease susceptibility to severe RRP in Koreans.

Comparison of 3 automated immunoassays for detection of anti-hepatitis A virus immunoglobulin M in a tertiary care hospital.

Three automated immunoassay kits for anti-Hepatitis A Virus (HAV) IgM-Architect, (Abbott Laboratories, USA), Elecsys (Roche Diagnostics, Germany), and ADVIA Centaur (Siemens Healthcare Diagnostics Inc., USA)-were compared. We included 178 consecutive samples, for which an anti-HAV IgM test was requested at Seoul National University Hospital from September 2009 to January 2010. Reviewing of medical records, reverse transcription (RT)-PCR for HAV RNA, or total anti-HAV assay were performed on 16 (9.0%) samples with discrepant results. The percent agreements (kappas) of the Architect and ADVIA Centaur, Architect and Elecsys, and ADVIA Centaur and Elecsys kits were 96.6% (0.91), 96.6% (0.92), and 97.8% (0.94), respectively. Eight out of 16 discrepant samples showed gray-zone values in Architect but were nonreactive in the others. Slightly earlier seroconversion was suspected in Elecsys. The 3 assays showed comparable performances with excellent agreements in a tertiary care hospital setting.

Comparison of three multiple allergen simultaneous tests: RIDA allergy screen, MAST optigen, and polycheck allergy.

We compared the performances of 3 Multiple Allergen Simultaneous Test (MAST) assays: RIDA Allergy Screen (R-Biopharm, Darmstadt, Germany), MAST Optigen allergy system (Hitachi Chemical Diagnostics, Mountain View, CA), and Polycheck Allergy (Biocheck GmbH, Munster, Germany). Forty sera that tested positive with the RIDA Allergy Screen (20 for food and 20 for inhalant panel) were subjected to MAST Optigen and Polycheck Allergy. For 26 available sera with discrepant results, 62 ImmunoCAP allergen-specific IgE tests (Pharmacia Diagnostics, Uppsala, Sweden) were performed. Percent agreements (kappa value) were 87.6% (0.59) and 91.3% (0.60) between RIDA and MAST; 89.9% (0.55) and 88.3% (0.46) between RIDA and Polycheck; and 86.8% (0.51) and 90.6% (0.61) between MAST and Polycheck. Compared with ImmunoCAP, agreements (kappa value) of inhalant and food panels were 51.7% (0.04) and 33.3% (-0.38) for RIDA; 60.7% (0.27) and 81.8% (0.59) for MAST; and 65.5% (0.26) and 45.5% (0.07) for Polycheck. The agreements between RIDA, MAST, and Polycheck and ImmunoCAP-positivity were 45.7%, 88.2%, and 28.6%, respectively, and the agreements for ImmunoCAP-negativity were 37.0%, 51.9%, and 88.9%. MAST Optigen showed better agreement with ImmunoCAP than other assays in the food panel. Better sensitivity of MAST Optigen and better specificity of Polycheck Allergy were suspected.

Beneficial effects of pretransplantation microchimerism on rejection-free survival in HLA-haploidentical family donor renal transplantation.

BACKGROUND: Fetal-maternal microchimerism (MC) can develop during pregnancy and may persist for decades. Pretransplantation fetal-maternal MC may be present between mother and child and between siblings; however, its effect on renal transplantation is not known. We investigated the effects of pretransplantation MC on allograft outcomes in human leukocyte antigen (HLA)-haploidentical family donor transplantation. METHODS: A total of 106 cases transplanted from 1996 to 2004 were retrospectively studied, with median follow-up of 96 months. The study and control groups included 63 and 43 cases of HLA-haploidentical and HLA-identical donor transplantations, respectively. MC against mismatched donor HLA-DRB1 allele was detected in the recipient's peripheral blood using nested polymerase chain reaction-single-strand conformation polymorphism method. The allograft outcomes of HLA-haploidentical MC (+) and (-) subgroups were compared with those of HLA-identical group. RESULTS: Pretransplantation MC in the HLA-haploidentical recipients was detected in 22.2% (14 of 63). Compared with HLA-identical group, MC (-) subgroup showed significantly inferior allograft outcomes: higher acute rejection rate (11.6% vs. 42.9%; P=0.001), higher 5-year serum creatinine level (1.1 vs. 1.4 mg/dL; P=0.009), and lower 10-year rejection-free survival rate (83.7% vs. 54.5%; log-rank P=0.001). In contrast, MC (+) subgroup showed no significant differences from HLA-identical group in acute rejection rate (14.3%), 5-year serum creatinine level (1.1 mg/dL), and 10-year rejection-free survival rate (85.7%). Multivariate analysis revealed that pretransplantation MC is associated with a significantly lower risk of acute rejection (odds ratio=0.10; P=0.021). CONCLUSION: Pretransplantation MC present in the recipient may have beneficial effects on rejection-free allograft survival in renal transplantation.

Characterization of sera with discordant results from reverse sequence screening for syphilis.

Reverse sequence screening for syphilis (RSSS) (screening with treponemal tests, followed by confirmation with nontreponemal tests) has been increasingly adopted. CDC recommends confirmation of discordant results (reactive EIA/CIA and nonreactive nontreponemal test) with Treponema pallidum particle agglutination assay (TP-PA). We characterized sera with discordant results from RSSS with Architect Syphilis TP CIA. Among 15,713 screening tests using Architect Syphilis TP at Seoul National University Gangnam Center between October 2010 and May 2011, 260 (1.7%) showed reactive results. Rapid plasma reagin (RPR) and TP-PA were performed on 153 available sera among them. On sera with discordant results between Architect Syphilis TP and TP-PA, INNO-LIA Syphilis Score and FTA-ABS were performed. Among 153 sera, RPR was nonreactive in 126 (82.4%). Among them, TP-PA was positive in 103 (81.7%), indeterminate (±) in 7 (5.6%), and negative in 16 (12.7%). Out of 16 CIA(+)/RPR(-)/TP-PA(-) sera, INNO-LIA Syphilis Score and/or FTA-ABS were negative on 14 sera. Out of 7 CIA(+)/RPR(-)/TP-PA(±) sera, INNO-LIA Syphilis Score and FTA-ABS were positive/reactive in 6 sera. RSSS with confirmation by TP-PA on sera with discordant results between Architect Syphilis TP and RPR effectively delineated those discordant results and could be successfully adopted for routine checkup for syphilis.

Differential cell death and Bcl-2 expression in the mouse retina after glutathione decrease by systemic D,L-buthionine sulphoximine administration.

Glutathione (GSH) plays a critical role in cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH decrease using [D, L]-buthionine sulphoximine (BSO) induces retinal cell death, but the underlying mechanisms of this are still unclear. Here, we demonstrated that retinal GSH level is closely related to retinal cell death as well as expression of an anti-apoptotic molecule, Bcl-2, in the retina. We induced differential expression of retinal GSH by single and multiple administrations of BSO, and examined retinal GSH levels and retinal cell death in vivo. Single BSO administration showed a transient decrease in the retinal GSH level, whereas multiple BSO administration showed a persistent decrease in the retinal GSH level. Retinal cell death also showed similar patterns: transient increases of retinal cell death were observed after single BSO administration, whereas persistent increases of retinal cell death were observed after multiple BSO administration. Changes in the retinal GSH level affected Bcl-2 expression in the retina. Immunoblot and immunohistochemical analyses showed that single and multiple administration of BSO induced differential expressions of Bcl-2 in the retina. Taken together, the results of our study suggest that the retinal GSH is important for the survival of retinal cells, and retinal GSH appears to be deeply related to Bcl-2 expression in the retina. Thus, alteration of Bcl-2 expression may provide a therapeutic tool for retinal degenerative diseases caused by retinal oxidative stress such as glaucoma or retinopathy.