HLA-A*31 como marcador de suscetibilidade genetica em sepse / HLA-A*31 as a marker of genetic susceptibility to sepsis

Objetivo: Haplótipos do HLA têm sido associados a muitas doenças autoimunes, mas não foi descrita qualquer associação na sepse. O objetivo desse estudo é investigar o sistema HLA como um possível marcador de suscetibilidade genética à sepse. Métodos: Estudo prospectivo de coorte, incluindo pacientes admitidos em unidade de terapia intensiva e controles-saudáveis obtidos em lista de doadores de transplante renal. Foram excluídos pacientes abaixo dos 18 anos de idade, gestantes ou HIV positivos, pacientes com doença maligna metastática ou sob quimioterapia, pacientes com hepatopatia avançada, com condições de fim de vida. O DNA foi extraído de sangue total, e a haplotipagem de HLA foi realizada com a tecnologia MiliPlex®. Resultados: Foram incluídos 1.121 pacientes (1.078 doadores de rim, 20 pacientes com sepse grave e 23 pacientes admitidos por choque séptico) entre outubro de 2010 e outubro de 2012. Os participantes positivos para HLA-A*31 tiveram risco aumentado de desenvolver sepse (OR: 2,36 IC95%: 1,26-5,35). Não foi identificada outra associação significativa, quando considerado como nível de significância o valor de p<0,01. Conclusão: A expressão de HLA-A*31 está associada ao risco de desenvolvimento de sepse. .

Objective: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility. Methods: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology. Results: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified. Conclusion: HLA-A*31 expression is associated to risk of developing sepsis. .

Identification of human leucocyte antigen -A* 0201-restricted hepatitis C virus-cytotoxic T lymphocyte epitopes / 中华传染病杂志

Objective To identify human leucocyte antigen (HLA)-A* 0201-restricted hepatitis C virus (HCV)-cytotoxic T lymphocyte (CTL) epitopes. Methods Based on the prediction results of RANKpep and SYFPEITHI prediction programs, six candidate CTL epitopes were selected and synthesized. The affinity of candidate CTL epitopes to HLA-A* 0201 molecules of T2 cells was explored. Subsequently, enzyme-linked immunosorbent spot (ELISPOT) assay and intracellular cytokine staining (ICS) were utilized to determine whether candidate CTL epitopes could induce the recall positive response in peripheral blood mononuclear cells (PBMC) of HLA-A* 0201 positive HCV-1b-infected patients. Results Among six candidate CTL epitopes, peptides C_181(LLSCLTTPV) and NS2_172 (VLQAGLIRV) had high affinity to HLA-A* 0201 molecules. Moreover, the affinity was proportional to the concentration of peptide. Furthermore, among ten HLA-A* 0201 positive HCV-1b-infected patients, the frequencies of C_181 and NS2_172-specific interferon (IFN)-γ-producing cells were 0-19 spots forming cells (SFC)/1 × 105 PBMC and 0-20 SFC/1 × 105 PBMC, respectively.The percentages of C_ 181 and NS2_172-specific IFN-γ+ CD8+ T lymphocytes in total CD8+ T lymphocytes were 0.006%-0.065% and 0.005%-0.080%, respectively. Conclusion Peptides C_181 (LLSCLTTPV) and NS2_172 (VLQAGLIRV) are identified as novel HLA-A* 0201-restricted HCV-CTL epitopes.

Relationship between human leukocyte antigen-A, -B alleles and psoriatic arthritis in Chinese Han population from Shandong Province / 中华皮肤科杂志

with PsA in Chinese Han population from Shandong Province.

Polymorphism of HLA-A and HLA-B in pre-eclampsia / 北京大学学报(医学版)

Objective: To investigate the association between the polymorphism of HLA-A, HLA-B genes and pre-eclampsia. Methods: HLA-A, HLA-B genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) in 119 preeclampsia patients, 117 normal pregnant women and their neonates. Results: The study showed that 16 HLA-A and 39 HLA-B alleles were obtained in pre-eclamptic patients and normal pregnant women. 15 HLA-A and 37 HLA-B alleles were obtained in their neonates. No significant difference was found in maternal or neonatal HLA-A, HLA-B alleles be-tween pre-eclampsia group and control group (Pc>0. 05). The frequencies of HLA-A11, HLA-A24,HLA-B13, HLA-B14, HLA-B15, HLA-B52 maternal/fetus genetic assoications were significantly different between pre-eclampsia group and control group (P<0. 05). Conclusion: Some HLA-A, HLA-B maternal/fetus special bindings may be associated with the susceptibility or protective of pre-eclampsia.

The association between HLA-A antigen carrying Bw4 epitope and HIV-1 viral loads and CD+4 T cell counts / 中华检验医学杂志

Objective To investigate the impact of HLA-A antigens carrying Bw4 epitopes on disease course of HIV-1 infection.Methods Three hundred and forty subjects chronically infected with HIV-I were recruited and their HLA-A and B alleles were genotyped with sequence-based high resolution typing assay.HLA-Bw genotypes of these HIV-1 infected subjects were determined and their association with CD+4 T cell counts and viral load were analysed.Results When compared with subjects canting no Bw4 epitopes in HLA-A and HLA-B loci (OBw4) (median of CD+4 T cell counts:294/μ1;plasma viral load median 6.29×104 copies/ml),CD+4 T cell counts in subjects with genotypes of 1Bw4-A and 2Bw4-AA were comparable (307 and 308/μ1,respectively),but higher viral load (1.53×105 and 2.68×105 copies/ml,respectively) was observed.In subjects with Bw4 epitopes in HLA-B alleles but no in HLA-A,significantly higher CD+4 T cell counts (417/μ1,P=0.013) and lower viral load (2.10×104 copies/ml,P=0.007) were observed compared with those without Bw4 in HLA-A and HLA-B.Conclusion HLA-B antigens carrying Bw4 epitope were protective in HIV-1 infection by maintaining higher CD+4 T cell counts and lower viral load,but such protective effect was not observed in HLA-A antigens earring Bw4 epitope.

Comparative study of HLA-A antigen typing by DNA chip and serology in 120 donor-recipients / 中华器官移植杂志

Objective To evaluate the accuracy and clinical practicality of DNA chip in comparison with serology in typing of human leukocyte antigen A (HLA-A) in Han's individuals of donor-recipients of transplantation. Methods 120 peripheral blood samples were obtained from donor-recipients of transplantation. Each sample was divided into two parts and HLA-A antigens were identified by DNA chip in one part and by serology in another. Samples in which the HLA-A typing results by these 2 methods were discordant were verified by polymerase chain reaction with sequence specific primers (PCR-SSP). Accuracy and clinical practicability of both methods were compared according to the typing results. Results Serological typing for HLA-A took 3 h, while DNA chip typing 4. 5-5 h. 112 samples have been typed successfully. Typing results were same in 91 samples and discordant in 21 cases. The verified results showed that DNA chip made 2 incorrect typing and the error rate was 2%. Meanwhile, serology made 19 mistakes, consisting of 5 antigens being incorrectly interpreted and 14 "blanks" turning out to be definable alleles. The discrepancy rate was 17 %. Conclusions DNA chip typing for HLA-A is suitable for clinical application in Chinese Han's population with a greater precision than serology. It may replace the serology in future after being improved and perfected.

Distribution of HLA-A, B alleles in patients with Guillain-Barr? syndrome / 中华神经科杂志

Objective To study the relations between the susceptibility to AIDP and AMAN, two forms of Guillain-Barr? syndrome (GBS), and the frequency of HLA-A, B alleles. Methods A case-control research was done in 31 cases of AIDP, 33 cases of AMAN and 132 health individual controls. DNA was extracted from peripheral blood leukocytes by improved fast saltingout. HLA-A, B antigens were typed by DNA-based technology, PCR-sequence specific primers (PCR-SSP) method. In determination of allelic polymorphism by PCR amplification with SSP, oligonucleotide primers are designed to obtain amplification of specific alleles or groups of alleles. Assignment of alleles is based on the presence or absence of PCR amplified product, which may be detected by agarose gel electrophoresis. Results On research of HLA-A, B alleles polymorphism, it showed that HLA-A33 frequency was increased significantly in AIDP patients [22.6% vs 4.5%,corrected probability (Pc)=0.011]; related risk (RR) was 6.1; HLA-B15, B35 frequencies were increased (51.7% vs 20.8%, Pc =0.015; 34.5% vs 6.9%, Pc=0.000 8); RR was 4.1 and 7.1, respectively. Conclusions There are different distribution of HLA-A, B alleles in AIDP and AMAN, two forms of GBS. AIDP susceptibility is associated with HLA-A33, while AMAN is with HLA-B15, B35.