Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 179
Filtrar
1.
Ann Lab Med ; 42(1): 54-62, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374349

RESUMO

Background: Associations between IgA nephropathy (IgAN) and HLA-DRB1 and -DQB1 alleles have been reported in several ethnic groups. We investigated the association of HLA-DRB1 and -DQB1 alleles with the predisposition for IgAN and disease progression to end-stage kidney disease (ESKD) in Korean patients. Methods: We analyzed HLA-DRB1 and -DQB1 genotypes in 399 IgAN patients between January 2000 and January 2019 using a LIFECODES sequence-specific oligonucleotide (SSO) typing kit (Immucor, Stamford, CT, USA) or a LABType SSO Typing Test (One Lambda, Canoga Park, CA, USA). Alleles with a significant difference in two-digit resolution were further analyzed using in-house sequence-based typing and sequence-specific primer PCR. As controls, 613 healthy hematopoietic stem cell donors were included. Kidney survival was analyzed in 281 IgAN patients with available clinical and laboratory data using Cox regression analysis. Where needed, P-values were adjusted using Bonferroni correction. Results: The allele frequencies of HLA-DRB1*04:05 (corrected P [Pc]<0.001), -DQB1 *04:01 (Pc=0.048), and -DQB1*03:02 (Pc=0.021) were significantly higher in IgAN patients than in controls, whereas those of HLA-DRB1*07:01, -DRB1*15:01, -DQB1*02:02, and -DQB1*06:02 (Pc<0.001 for all) were significantly lower in IgAN patients than in controls. The allele frequency of HLA-DQB1*05:03 (Pc=0.016) was significantly lower in the ESKD group than in the non-ESKD group; however, there was no significant difference for ESKD progression between these groups. Conclusions: We report novel associations of HLA-DRB1*15:01, DQB1*02:02, -DQB1*03:02, and -DQB1*04:01 with IgAN. Further studies of HLA alleles associated with IgAN progression in a larger cohort and in various ethnic groups are needed.


Assuntos
Glomerulonefrite por IGA , Alelos , Predisposição Genética para Doença , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/genética , Cadeias HLA-DRB1/genética , Teste de Histocompatibilidade , Humanos , República da Coreia
2.
J Clin Lab Anal ; 35(9): e23921, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34369009

RESUMO

BACKGROUND: SARS-CoV-2 pandemic is currently ongoing, meanwhile vaccinations are rapidly underway in some countries. The quantitative immunoassays detecting antibodies against spike antigen of SARS-CoV-2 have been developed based on the findings that they have a better correlation with the neutralizing antibody. METHODS: The performances of the Abbott Architect SARS-CoV-2 IgG II Quant, DiaSorin LIAISON SARS-CoV-2 TrimericS IgG, and Roche Elecsys anti-SARS-CoV-2 S were evaluated on 173 sera from 126 SARS-CoV-2 patients and 151 pre-pandemic sera. Their correlations with GenScript cPass SARS-CoV-2 Neutralization Antibody Detection Kit were also analyzed on 173 sera from 126 SARS-CoV-2 patients. RESULTS: Architect SARS-CoV-2 IgG II Quant and Elecsys anti-SARS-CoV-2 S showed the highest overall sensitivity (96.0%), followed by LIAISON SARS-CoV-2 TrimericS IgG (93.6%). The specificities of Elecsys anti-SARS-CoV-2 S and LIAISON SARS-CoV-2 TrimericS IgG were 100.0%, followed by Architect SARS-CoV-2 IgG II Quant (99.3%). Regarding the correlation with cPass neutralization antibody assay, LIAISON SARS-CoV-2 TrimericS IgG showed the best correlation (Spearman rho = 0.88), followed by Architect SARS-CoV-2 IgG II Quant and Elecsys anti-SARS-CoV-2 S (all rho = 0.87). CONCLUSIONS: The three automated quantitative immunoassays showed good diagnostic performance and strong correlations with neutralization antibodies. These assays will be useful in diagnostic assistance, evaluating the response to vaccination, and the assessment of herd immunity in the future.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/virologia , Imunoensaio/métodos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Neutralizantes/sangue , Teste Sorológico para COVID-19/instrumentação , Humanos , Imunoglobulina G/sangue , Testes de Neutralização , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Testes Sorológicos
3.
Exp Cell Res ; 405(2): 112705, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34166678

RESUMO

The interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) pathway modulates immune response and inflammation, associated with allograft dysfunction and rejection. We hypothesized that IL-33/ST2 is a marker of renal allograft rejection and IL-33/ST2 expression may differ according to rejection type. IL-33/ST2 expression was measured in sera and kidney tissues from recipients with acute antibody-mediated rejection (AAMR), acute cell-mediated rejection (ACMR), chronic antibody-mediated rejection (CAMR), and healthy controls. The soluble ST2 and IL-33/ST2 expression levels were higher in participants with all three rejection types than in controls. Although the expression levels in recipients with AAMR and ACMR were significantly higher than those with CAMR, there was no significant difference between the expression levels in AAMR and ACMR. Although IL-33, IL-8, and fibronectin expression were significantly increased after the addition of the recipients' serum in primary cultured human renal proximal tubular epithelial cells, the levels decreased after treatment with an anti-ST2 antibody. Furthermore, the anti-ST2 antibody specifically suppressed the upregulation of the mixed lymphocyte reaction. Boyden chamber assays demonstrated that anti-ST2 antibody abrogated chemotaxis induced by recombinant IL-33. Thus, IL-33 and ST2 are potent mediators of rejection. Treatment with an anti-ST2 antibody ameliorates rejection and could be a potential therapeutic strategy for renal allograft rejection.


Assuntos
Aloenxertos/imunologia , Rejeição de Enxerto/imunologia , Interleucina-33/metabolismo , Transplante de Rim , Adulto , Anticorpos/farmacologia , Biomarcadores/análise , Feminino , Humanos , Rim/imunologia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/métodos
4.
Clin Lab ; 67(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491440

RESUMO

BACKGROUND: For HLA genotyping, PCR sequence-specific oligonucleotide (SSO) methods using the Luminex platform are widely used. We evaluated the performance of LabType-SSO (One Lambda, USA) in Koreans. METHODS: LabType-SSO were performed on 50 residual DNA samples analyzed by sequence-based typing (SBT) for all HLA-A, -B, -C, -DRB1, and -DQB1 alleles with gene frequency > 0.1% in Koreans. RESULTS: The LabType-SSO results were in complete agreement with SBT at the 2-digit level. For 4-digit level, 9 HLA-A alleles, 1 HLA-B allele, 3 HLA-C alleles, neither HLA-DRB1 nor -DQB1 allele showed ambiguous results for assignment of most probable types considering HLA gene frequency in Koreans. In addition, two cases of DQB1*04:01 allele were incorrectly assigned to DQB1*04:02. CONCLUSIONS: LabType-SSO tests showed accurate assignment of 2-digit level and LabType-SSO HLA-DRB1 test showed correct 4-digit most probable HLA type. The tests can be useful as intermediate resolution typing for solid organ transplantation.


Assuntos
Antígenos HLA-A , Oligonucleotídeos , Alelos , Frequência do Gene , Antígenos HLA-A/genética , Cadeias HLA-DRB1/genética , Haplótipos , Teste de Histocompatibilidade , Humanos
5.
J Clin Lab Anal ; 35(3): e23671, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33283340

RESUMO

BACKGROUND: Although a diagnosis of infectious diseases is essential for timely treatment, the performance of diagnostic tests has been hardly evaluated due to variable results that are influenced by multiple factors in different conditions. In the present study, the performance of the Alinity i system, which is a newly developed immunoassay to diagnose infectious diseases, was evaluated. METHODS: We evaluated the precision, linearity, correlation, and carryover of 16 analytes (HAV Ab IgG, HBsAg, HBeAg, anti-HBc, anti-HBe, anti-HBs, anti-HCV, HIV Ag/Ab, EBV VCA IgM, EBV VCA IgG, EBV EBNA IgG, CMV IgM, CMV IgG, Toxoplasma IgG, Rubella IgG, and Syphilis TP) of Alinity i by comparison with ARCHITECT i2000SR system following the rationale of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: For quantitative tests, the coefficients of variation (CV) % of repeatability and intermediate precision were between 0% and 4.18%. The coefficients of the linearity (r2 ) over a widely tested analytical range were ≥ 0.990 and the correlation between Alinity i and the ARCHITECT i2000SR system was strong (r ≥ 0.994). For qualitative tests, the agreement between Alinity i and the ARCHITECT i2000SR system was excellent (kappa coefficient 1) with 100% sensitivity and specificity. Carryover rates for all analytes were less than 1.0% (-0.11% ~ 0.21%). CONCLUSION: The Alinity i system showed good analytical performance and favorable comparability with the ARCHITECT i2000SR. It could be suitable as a routine immunoassay analyzer for screening and diagnosis of infectious disease.

6.
Cell Transplant ; 29: 963689720926151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32623908

RESUMO

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs. We analyzed a total of 27,904 Korean CBUs donated to the public CB bank. Low-to-intermediate resolution typing was performed for HLA-A, -B, and -DRB1 alleles, and individuals possessing homozygous HLA haplotypes were identified by direct counting. Moreover, the matching probabilities for zero-mismatch transplantation were calculated for 27,904 CBUs and 50,000,000 potential Korean patients. Among the preserved CBUs, 15 HLA-A, 40 HLA-B, and 13 HLA-DRB1 alleles as well as 48 homozygous HLA-A-B-DRB1 haplotypes were identified at serological equivalents (2 digits). The 48 identified homozygous haplotypes cumulatively matched 78.18% of the 27,904 Korean CB donors as zero HLA-mismatch iPSC sources. Among the combinations of 1,699 haplotypes with frequencies greater than 0.001%, assuming a population of 50 million, those 48 haplotypes can provide a match for 78.37% of potential Korean recipients. A practicable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs may be an efficient option in allogeneic iPSC therapy because this type of haplobanking may provide cell lines with optimal HLA matching for up to three-quarters of the Korean population.


Assuntos
Bancos de Sangue/normas , Criopreservação/métodos , Sangue Fetal/química , Células-Tronco Pluripotentes Induzidas/metabolismo , Humanos
7.
Transfus Apher Sci ; 59(5): 102849, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32616364

RESUMO

According to the increase in both the number of cryopreserved cord blood (CB) units and the cryopreservation period for each CB unit in the largest public CB bank in Korea, we are pursuing greater efficiency in CB bank management. Thus, we analyzed whether the cryopreservation period has a negative impact on the selection of CB units for CB transplantation (CBT). Until December 2019, 468 CB units were used for transplantation. The cryopreservation period, total nucleated cell (TNC), and CD34+ cell counts were analyzed among the CB units according to the CBT-year and the donation year. The results showed that the cryopreservation period was increased in recent CBT-year groups. The transplanted CB units showed similar TNC counts irrespective of the donation year, and the mean TNC count was 13.9 × 108/unit. CB units cryopreserved for a relatively long period were transplanted consistently. The mean TNC count of CB units cryopreserved for over 10 years was 16.4 × 108/unit. The mean CD34+ cell counts were not significantly different among the CB units transplanted after CBT-2013 and among the CB units donated after CBT-2011. Through an analysis of the CB units selected by clinicians for CBT, this study revealed that clinicians placed more weight on the TNC counts than on the cryopreservation period of cryopreserved CB units. Therefore, the minimum TNC count of CB units suitable for cryopreservation should be increased up to 13.0 × 108/unit to balance the satisfaction of clinicians' needs with the efficiency of the CB bank.

8.
Biol Blood Marrow Transplant ; 26(8): e202-e208, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32439474

RESUMO

Induced pluripotent stem cells (iPSCs) have opened up unprecedented opportunities for novel therapeutic options for precision medicine. Hematopoietic stem cell (HSC) donor pools with previously determined HLA types may be ideal sources for iPSC production. Based on the HLA distribution of cryopreserved cord blood units (CBUs) and registered bone marrow (BM) donors, we estimated how much of the Korean population could be covered by HLA-homozygous iPSCs. We analyzed a total of 143,866 Korean HSC donors (27,904 CBUs and 115,962 BM donors). Each donor sample was typed for the HLA-A, -B, and -DRB1 alleles at low to intermediate resolution by DNA-based molecular techniques: PCR sequence-specific oligonucleotide (PCR-SSOP), PCR with sequence-specific primers (PCR-SSP) and PCR with sequence-based typing (PCR-SBT). We also identified individuals possessing homozygous HLA haplotypes by direct counting. The matching probabilities for zero-mismatch transplantation were calculated for 143,866 Koreans and 50 million potential Korean patients. Among the HSC donor pool, 17 HLA-A alleles, 41 HLA-B alleles, and 13 HLA-DRB1 alleles, as well as 128 homozygous HLA-A-B-DRB1 haplotypes, were identified at serologic equivalents, and those haplotypes cumulatively matched 93.20% of the 143,866 Korean donors as zero HLA-mismatch iPSC sources. Among the combinations of 2,056 haplotypes with frequencies ≥ 0.001% in a population of 50 million, those 128 homozygous haplotypes can provide 93.65% coverage for potential Korean recipients. Haplobanking of a reasonable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs and cells of registered BM donors may be an efficient option for allogenic iPSC therapy.


Assuntos
Células-Tronco Pluripotentes Induzidas , Alelos , Medula Óssea , Sangue Fetal , Cadeias HLA-DRB1/genética , Haplótipos , Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Sistema de Registros , Doadores de Tecidos
9.
Ann Clin Lab Sci ; 50(2): 247-252, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32366564

RESUMO

The association of anti-MHC class I-related chain A (MICA) and kidney allograft rejection has been reported. However, the associations of antibodies specific to donor MICA (dsMICA) and dsMICA levels with allograft outcome have not been elucidated. From November 2009 to June 2017, 125 sera samples from renal transplantation recipients with no HLA antibodies were screened for MICA antibodies. Patients with positive MICA antibody screening results and available residual donor DNA for MICA geno-typing underwent dsMICA analysis. Among these 125 sera samples, 19 were positive for MICA antibodies. dsMICA was positive in 5 out of the 12 analyzed sera samples. Neither MICA antibodies nor dsMICA were associated with acute rejection. However, interstitial fibrosis and tubular atrophy (IFTA) was significantly associated with MICA antibody positivity (OR=3.84, P=0.009). In addition, the MFI value of dsMICA was significantly higher in patients with IFTA II or III than in patients without IFTA II or III (P=0.009). The association of MICA antibodies and dsMICA with high grade IFTA (grade II or III) was suggested. The MICA antibody and dsMICA might be useful indicators of chronic renal damage.


Assuntos
Anticorpos/sangue , Formação de Anticorpos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Transplante de Rim/efeitos adversos , Aloenxertos , Feminino , Rejeição de Enxerto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doadores de Tecidos
10.
J Korean Med Sci ; 35(12): e78, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32233158

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) typing is important for transplant patients to prevent a severe mismatch reaction, and the result can also support the diagnosis of various disease or prediction of drug side effects. However, such secondary applications of HLA typing results are limited because they are typically provided in free-text format or PDFs on electronic medical records. We here propose a method to convert HLA genotype information stored in an unstructured format into a reusable structured format by extracting serotype/allele information. METHODS: We queried HLA typing reports from the clinical data warehouse of Seoul National University Hospital (SUPPREME) from 2000 to 2018 as a rule-development data set (64,024 reports) and from the most recent year (6,181 reports) as a test set. We used a rule-based natural language approach using a Python regex function to extract the 1) number of patients in the report, 2) clinical characteristics such as indication of the HLA testing, and 3) precise HLA genotypes. The performance of the rules and codes was evaluated by comparison between the extracted results from the test set and a validation set generated by manual curation. RESULTS: Among 11,287 reports for development set and 1,107 for the test set describing HLA typing for a single patient, iterative rule generation developed 124 extracting rules and 8 cleaning rules for HLA genotypes. Application of these rules extracted HLA genotypes with 0.892-0.999 precision and 0.795-0.998 recall for the five HLA genes. The precision and recall of the extracting rules for the number of patients in a report were 0.997 and 0.994 and those for the clinical variable extraction were 0.997 and 0.992, respectively. All extracted HLA alleles and serotypes were transformed according to formal HLA nomenclature by the cleaning rules. CONCLUSION: The rule-based HLA genotype extraction method shows reliable accuracy. We believe that there are significant number of patients who takes profit when this under-used genetic information will be return to them.


Assuntos
Antígenos HLA/genética , Teste de Histocompatibilidade , Armazenamento e Recuperação da Informação , Processamento de Linguagem Natural , Algoritmos , Data Warehousing , Registros Eletrônicos de Saúde , Genótipo , Humanos , Seul
11.
Sci Rep ; 10(1): 6425, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286398

RESUMO

An immunosuppressant weaning protocol in failing allografts has not yet been established. Maintaining immunosuppressants would preserve residual renal function (RRF) and prevent graft intolerance syndrome and sensitization but would increase the risks of infection and malignancy. In this study, graft failure cases after kidney transplantation in a single center were reviewed retrospectively. The outcome differences in all-cause mortality, infection-related hospitalization, cancer, graft intolerance syndrome, re-transplantation, and RRF duration between the immunosuppressant maintaining and weaning groups 6 months after graft failure were compared. Among the weaning group, the outcome differences according to low-dose steroid use were also compared at 6 and 12 months. In a total of 131 graft failure cases, 18 mortalities, 42 infection-related hospitalizations, 22 cancer cases, 11 graft intolerance syndrome cases, and 28 re-transplantations occurred during the 94-month follow-up. Immunosuppressant maintenance significantly decreased the patient survival rate 6 months after graft failure compared with weaning (log-rank P = 0.008) and was an independent risk factor for mortality, even after adjustments (hazard ratio, 3.01; P = 0.025). Infection-related hospitalization, graft intolerance syndrome development, and re-transplantation were not affected by the immunosuppressant weaning protocol. Among the immunosuppressant weaning group, low-dose steroid maintenance at 6 and 12 months helped preserved RRF (P = 0.008 and P = 0.003, respectively).


Assuntos
Imunossupressores/uso terapêutico , Falência Renal Crônica/etiologia , Transplante de Rim/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Esteroides/uso terapêutico , Resultado do Tratamento , Adulto Jovem
13.
Clin Lab ; 66(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32013363

RESUMO

BACKGROUND: Plasmapheresis (PP) is commonly used for desensitization in highly sensitized patients with donor-specific antibodies (DSA) in living donor kidney transplantation. We analyzed the impact of DSA levels before and after desensitization on renal allograft outcome. METHODS: Twenty-three patients who underwent desensitization with PP, intravenous immunoglobulin (IVIG), and rituximab before kidney transplantation in Seoul National University Hospital from August 2006 to August 2016 were enrolled. The association of median fluorescent intensity (MFI) value of DSA with graft outcome was analyzed. RESULTS: The frequency of positive HLA class II DSA after desensitization was lower in patients without antibody-mediated rejection (AMR) compared to those with AMR (p = 0.006). The cutoff value of MFI sum of HLA class II DSA after desensitization for predicting AMR was 2,122 with 63% sensitivity and 94% specificity. The frequency of moderate HLA class II DSA (MFI 5,000 - 10,000) after desensitization was significantly higher in patients with graft loss compared to those without graft loss (p = 0.02). CONCLUSIONS: Weak HLA class II DSA after desensitization including PP, IVIG, and rituximab was related to AMR and moderate levels of HLA class II DSA after desensitization was related to graft loss in living donor kidney transplantation.


Assuntos
Anticorpos , Dessensibilização Imunológica/métodos , Transplante de Rim/métodos , Doadores Vivos , Anticorpos/sangue , Anticorpos/imunologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Plasmaferese , Rituximab/uso terapêutico
14.
Ann Clin Lab Sci ; 49(5): 678-681, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31611215

RESUMO

Recently, the removal of false reaction from beads 10 (DRB1 *04:04), 30 (DRB1 *16:01), and 31 (DRB1 *16:02) by fetal bovine serum (FBS) treatment in LABScreen Single Antigen Class II Assay was reported. We aimed to confirm the reaction in many cases. Fifty-nine sera showed positivity on at least two among beads 10, 30 and 31 from Nov 2017 to Oct 2018 in Seoul National University Hospital were included. FBS treatment was performed on 59 sera, and Single Antigen Class II Assay was repeated. Among 59 cases, the negative conversion rates of DR16 (57/59, 96.6%), DR4 (37/39, 94.9%), and accompanied other antibodies, e.g.) DP19 (39/45, 86.7%) were very high. The prior use of intravenous immunoglobulin in a non-specific binding group was significantly higher than the sex, age-matched control group (P=0.005).


Assuntos
Feto/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Imunoensaio/métodos , Soro/metabolismo , Adulto , Animais , Estudos de Casos e Controles , Bovinos , Feminino , Humanos , Masculino
15.
J Viral Hepat ; 26(11): 1318-1329, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31243853

RESUMO

Recently, HLA class II loci, including HLA-DPB1, have been reported to be associated with interindividual variance in the hepatitis B (HB) vaccine response. In this study, we investigated significant single nucleotide polymorphisms (SNPs) for anti-HBs antibody levels in 6867 healthy Koreans using a genome-wide association study (GWAS). In GWAS, the top 20 SNPs that showed significant association with anti-HBs levels (P < 1.0 × 10-29 ) all resided in HLA-DPB1. Utilizing PCR sequencing, we verified the relationship of the top 3 most significant SNPs (rs1042169, rs9277355 and rs9277356) from the GWAS and genotypes of HLA-DPB1 with the HB vaccine response in Korean infants who received a scheduled vaccination. The DPB1*04:02 allele has G, C and A nucleotides for the 3SNP sites, and was significantly more frequent in responders than in nonresponders (10.9% vs 1.0%, Pc  = 0.018). DPB1*05:01 was significantly more frequent in nonresponders than in responders (49.0% vs 31.1%, Pc  = 0.018). In multivariate logistic regression, DPB1*04:02 showed a significant association with both vaccine response (P = 0.037, OR = 8.465) and high-titre response (P = 0.027, OR = 9.860). The haplotypes rs1042169 G - rs9277355 C - rs9277356 A showed a significant association with a high-titre response only (P = 0.002, OR = 2.941). In conclusion, DPB1*04:02 possessing rs1042169 G - rs9277355 C - rs9277356 A is an independent predictor of the HB vaccine response in Koreans.


Assuntos
Variação Genética , Estudo de Associação Genômica Ampla , Cadeias beta de HLA-DP/genética , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/genética , Hepatite B/prevenção & controle , Fatores Etários , Alelos , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Feminino , Genótipo , Haplótipos , Anticorpos Anti-Hepatite B/imunologia , Humanos , Lactente , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Controle de Qualidade , República da Coreia/epidemiologia , Fatores de Risco
16.
Semin Arthritis Rheum ; 49(2): 283-287, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30952422

RESUMO

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.


Assuntos
Autoanticorpos , Predisposição Genética para Doença , Cadeias beta de HLA-DP/genética , Cadeias HLA-DRB1/genética , Miosite/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , República da Coreia
17.
Am J Transplant ; 19(10): 2855-2864, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31017369

RESUMO

With the recent update to the Oxford classification for allograft IgA nephropathy (IgAN), additional investigations on the clinical significance of the updated components are warranted. We performed a retrospective cohort study at two tertiary hospitals. Kidney transplant recipients diagnosed with allograft IgAN were included in the study after additional review by specialized pathologists. We applied the updated Oxford classification and determined the MEST-C scores of the patients. The main study outcome was death-censored graft failure within 10 years after the establishment of allograft IgAN diagnosis and was assessed using the Cox regression analysis. Three hundred thirty-three allograft IgAN patients were reviewed: 100 patients with confirmed native IgAN and 233 patients with other, clinical, or unknown primary causes for end-stage renal disease (ESRD). The updated Oxford classification for allograft IgAN demonstrated prognostic value for graft failure, and patients with multiple MEST-C components had worse outcomes. M, E, S, and C were significantly associated with the prognosis of recurred IgAN and T was the only independent prognostic parameter for allograft IgAN without confirmed native IgAN. Therefore, we suggest reporting MEST-C scores in allograft biopsies and careful interpretation of the results according to the primary cause of ESRD.


Assuntos
Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/diagnóstico , Rejeição de Enxerto/diagnóstico , Falência Renal Crônica/patologia , Transplante de Rim/efeitos adversos , Rim/patologia , Complicações Pós-Operatórias/diagnóstico , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/etiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo
18.
Leuk Lymphoma ; 60(7): 1775-1781, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30507323

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only treatment option for acute myeloid leukemia (AML) refractory to induction chemotherapy, with only 10-20% of patients achieving long-term survival. Certain donor genotypes may confer leukemia-clearing effects after allo-HSCT. We performed whole-exome sequencing of five pairs of the germ lines in AML patients who achieved long-term remission after allo-HSCT and in their donors, and found two significant variants: EGFR c.2982C > T and CDH11 c.945G > A. To validate the protective effects of these leukemia-clearing genotypes (LCGs), AML patients who received allo-HSCT in a complete-remission status were also analyzed. Twenty-two of 96 donors (22.9%) had LCGs in their genomes, and overall survival was significantly longer in patients who received allo-HSCT from donors with germ-line LCGs (hazard ratio=0.47, 95% confidence interval=0.24-0.94, p = .033). These findings indicate that donor germ-line LCGs have phenotypically leukemia-clearing effects and are biomarkers for predicting clinical outcomes in allogeneic transplantation in AML patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Recidiva Local de Neoplasia/mortalidade , Doadores não Relacionados/estatística & dados numéricos , Adulto , Caderinas/genética , Terapia Combinada , Receptores ErbB/genética , Feminino , Seguimentos , Genótipo , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Sequenciamento Completo do Exoma , Adulto Jovem
19.
Sci Rep ; 8(1): 18064, 2018 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-30584253

RESUMO

The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replication set. The patient genomes in the discovery set were sequenced using WES. Also, known tacrolimus pharmacokinetics-related intron variants were genotyped. Tacrolimus C0/D was log-transformed. Sixteen variants were identified including novel CYP3A7 rs12360 and rs10211 by ANOVA. CYP3A7 rs2257401 was found to be the most significant variant among the periods by ANOVA. Seven variants including CYP3A7 rs2257401, rs12360, and rs10211 were analyzed by SNaPshot in the replication set and the effects on tacrolimus C0/D were verified. A linear mixed model (LMM) was further performed to account for the effects of the variants and clinical factors. The combined set LMM showed that only CYP3A7 rs2257401 was associated with tacrolimus C0/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C0/D in those expressing CYP3A5, showing its own effect. The results suggest that CYP3A7 rs2257401 may serve as a significant genetic marker for tacrolimus pharmacokinetics in kidney transplantation.


Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/sangue , Transplante de Rim , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Tacrolimo/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplantados , Sequenciamento Completo do Exoma
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...