The best time of tumor intervention is before the formation of tumor. However,due to the limited number of tumor cells,it is difficult to quantify tumor cells and immunity by the current methods available( such as CTC,ct DNA). This affects the tumor prevention in this period,and the in-depth detection,intervention and evaluation of traditional Chinese medicine( TCM)( tumor) prevention. Due to the limitations of the current detection,the evaluation system turns to detect tumor neoantigen-specific CTL( naCTL) that are directly relating to tumor cells and proliferate to high order of magnitudes after activation,and immune repertoire( TCR/BCR/HLA) effective diversity,introduces immune checkpoints,uses information of " disease" in Western medicine and " syndrome" in TCM( prevention),and sets up a multi-dimensional statistical immunity model using a variety of data analysis and related algorithms. This model can amplify the ultra-early information of tumor,indirectly evaluate the quantity and status of tumor cells,and provide quantitative measurement and new evaluation methods for the normalization of immunity and TCM( tumor) prevention. This model is not only one of important evaluation methods for resisting tumor immunity and treating TCM( tumor) prevention,but also will reveal the scientific connotation of TCM syndrome from the perspective of immunology.
Drugs, Chinese Herbal ; HLA Antigens ; Humans ; Medicine, Chinese Traditional ; Neoplasms ; immunology ; prevention & control ; Receptors, Antigen, B-Cell ; Receptors, Antigen, T-Cell

<b>Objective:b> To understand the disease progression and human leukocyte antigen (HLA) gene polymorphism of HIV-infected persons without disease progress for long term, also known as long-term non-progressors (LTNPs), in Henan province. <b>Methods:b> A retrospective study was conducted in 48 LTNPs with complete detection and follow-up information during 2011-2016 in Henan. Changes of CD(4)(+)T cells counts (CD(4)) and viral load (VL) during follow-up period were discussed. Polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) was used for the analyses of HLA-A, HLA-B and HLA-DRB1 alleles between LTNPs and healthy controls. <b>Results:b> From 2011 to 2016, forty-eight LTNPs showed a decrease of the quartile (P(25)-P(75)) of CD(4) from 601.00 (488.50-708.72)/μl to 494.00 (367.00-672.00)/μl, and the difference was significant (P<0.05). The increase of the quartile (P(25)-P(75)) of log(10)VL from 3.40 (2.87-3.97) to 3.48 (2.60-4.37), but the difference was not significant (P>0.05). HLA polymorphism analysis revealed that HLA-B*13:02 and HLA-B*40:06 were more common in LTNPs (P<0.05), while HLA-B*46:01 and HLA-DRB1*09:01 were more common in healthy controls (P<0.05). <b>Conclusions:b> The CD(4) of LTNPs in Henan showed a downward trend year by year. HLA-B*13:02 and B*40:06 might be associated with delayed disease progression for HIV infected persons in Henan.
Adult ; Alleles ; Asian People/genetics* ; China ; Disease Progression ; Female ; HIV ; HIV Infections/virology* ; HIV-1/immunology* ; HLA-B Antigens/genetics* ; Humans ; Middle Aged ; Polymorphism, Genetic ; Retrospective Studies ; Viral Load

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.
Adult ; Aged ; *Alleles ; Allopurinol/adverse effects/*pharmacology ; Anticonvulsants/*adverse effects ; Asian Continental Ancestry Group/*genetics ; Carbamazepine/adverse effects/*pharmacology ; Case-Control Studies ; Drug-Related Side Effects and Adverse Reactions/*genetics/immunology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; HLA-B Antigens/*genetics ; Humans ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stevens-Johnson Syndrome/ethnology/etiology/*genetics ; Triazines/adverse effects/*pharmacology

Alleles ; Crystallography, X-Ray ; HIV Infections ; HIV-1 ; HLA-B Antigens ; chemistry ; immunology ; Humans

The purpose of this study was to evaluate the potential associations between HLA-A, B, DRB1 gene and leukemia. A total of 1186 leukemic patients, including 326 patients with acute lymphoblastic leukemia (ALL), 545 patients with acute myeloid leukemia (AML), 315 patients with chronic myeloid leukemia (CML), and 1234 healthy unrelated donors were typed and were compared in a single centre by using same technique, then the Bonferroni correction method was used to correct the Type I error. The results indicated that as compared with the control,the frequency of HLA-DRB1(*)09 in ALL group significantly decreased (10.87% versus 16.08%; Pc = 0.014, OR = 0.637, 95% CI = 0.487-0.834), while in comparison with control, the frequency of HLA-B(*)18 in CML group was significantly higher (1.28% vs 0.20%; Pc = 0.039, OR = 6.336, 95% CI = 2.066-19.434). The positive and negative relation may exist between certain HLA molecules and leukemia. The negative relation between HLA-DRB1(*)09 and ALL indicated that DRB1*09 might play an important role by a restricted T-cell immune response in the early leukemogenic events, whereas the positive relation between HLA-B(*)18 and CML suggests that the B(*)18 molecules may not actively present leukemia-specific antigens resulting in immune escape. It is concluded that these findings can contribute to developing more appropriate method in leukemic immunotherapy.
Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; HLA-DRB1 Chains ; genetics ; Histocompatibility Testing ; Humans ; Infant ; Leukemia ; genetics ; immunology ; therapy ; Major Histocompatibility Complex ; genetics ; Middle Aged ; Retrospective Studies ; Tumor Escape ; Young Adult

Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141-149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.
Adult ; Amino Acid Sequence ; Animals ; Binding Sites ; Epitopes ; chemistry ; immunology ; metabolism ; Female ; Genotype ; HEK293 Cells ; HLA-A2 Antigen ; metabolism ; Hepatitis B Core Antigens ; chemistry ; immunology ; metabolism ; Hepatitis B virus ; genetics ; metabolism ; Humans ; Hydrogen Bonding ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Middle Aged ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.
Alleles ; Allopurinol ; adverse effects ; Anti-HIV Agents ; adverse effects ; Anticonvulsants ; adverse effects ; Carbamazepine ; adverse effects ; Dideoxynucleosides ; adverse effects ; Drug Hypersensitivity Syndrome ; etiology ; immunology ; Drug-Related Side Effects and Adverse Reactions ; genetics ; immunology ; Enzyme Inhibitors ; adverse effects ; Genome-Wide Association Study ; HLA Antigens ; genetics ; HLA-B Antigens ; immunology ; HLA-B15 Antigen ; immunology ; Humans ; Stevens-Johnson Syndrome ; etiology ; immunology

<b>OBJECTIVEb>To compare the effects of Bushen Jiedu Recipe (BJR) and Jianpi Jiedu Recipe (JJR) containing plasma on dendritic cells (DCs) of chronic hepatitis B virus (HBV) infection patients under different immune states.

<b>METHODSb>Recruited were 36 chronic HBV infection outpatients from First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from April 2010 to January 2011. They were assigned to the immune tolerance group (18 cases) and the immune clearance group (18 cases).Another 10 healthy subjects were recruited as the healthy control group. Their anticoagulated peripheral venous blood was respectively collected. The peripheral blood mononuclear cells (PBMCs) were isolated and further extracted for incubating DCs. The DCs were intervened by BJR and JJR containing plasma. The morphology of DCs was identified. The expressions of CD1alpha, CD80, CD86, and HLA-DR were detected. The level of interferon-alpha (IFN-alpha) in the supernatant was observed by ELISA.

<b>RESULTSb>The CD80 expression level was lower in the immune clear group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, CD86, and HLA-DR were lower in the immune tolerance group than in the healthy control group before intervention (P < 0.05).The IFN-alpha expression level was lower in the immune tolerance group and the immune clearance group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, HLA-DR, and IFN-alpha were lower in the immune tolerance group than in the immune clearance group before intervention (P < 0.05). Compared with the same group before intervention, the CD80 expression significantly increased in each treatment group (P < 0.05). After intervention the expression levels of CD80 and HLA-DR were higher in the immune tolerance group than in the immune clearance group in the same time phase, and the CD86 expression level was higher in the BJR group than in the immune clearance group in the same time phase, showing statistical difference (P < 0.05).

<b>CONCLUSIONSb>The middle dose BJR and the small dose JJR both could promote the recovery of DCs in chronic HBV infection patients. Besides, BJR showed more prominent effects on the function of DCs in chronic HBV infection patients in the immune tolerance stage.

Adult ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; Case-Control Studies ; Dendritic Cells ; drug effects ; immunology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; HLA-DR Antigens ; metabolism ; Hepatitis B, Chronic ; blood ; drug therapy ; immunology ; Humans ; Immune Tolerance ; drug effects ; Interferon-alpha ; metabolism ; Male ; Phytotherapy ; Plasma ; Young Adult

BACKGROUND: Introduction of the Luminex panel reactive antibody (PRA)-single antigen (SA) assay has increased the detection rates of unacceptable antigens in sensitized patients; the calculated PRA (CPRA) level represents the percentage of actual organ donors that express 1 or more of these unacceptable antigens. We developed a CPRA calculator based on the HLA frequencies in Koreans to measure sensitization levels in Korean patients. METHODS: To develop the calculator, we obtained the HLA-A, HLA-B, and HLA-DR phenotypes of 1,622 Koreans, and compared these with previously reported frequencies in Koreans. Sera from patients awaiting kidney transplantation were tested for HLA antibodies by Luminex PRA-screen, PRA-identification (ID), and PRA-SA assays. The measured %PRA from the PRA-screen (N=55) and PRA-ID (N=71) were compared to the %CPRA for the unacceptable antigens obtained from PRA-SA. RESULTS: Phenotype frequencies used for the CPRA calculator agreed with previously reported data. The concordance rates among the 3 PRA methods for the detection of class I and class II antibodies were 76.1-81.8% (kappa, 0.519-0.636) and 72.7-83.6% (0.463-0.650), respectively. For the detection of broadly sensitized sera (>50% or >80%), the concordance rates were over 80%. In sera with 80-100% CPRA, 91.7% and 94.4% of the samples had concordant results (80-100% PRA) in the PRA-screen and PRA-ID assay, respectively. CONCLUSIONS: Although further clinical studies are required to confirm the benefits of CPRA values, adoption of CPRA analysis based on HLA frequencies in Koreans may be useful for sensitization measurements and organ-allocation algorithms.
*Algorithms ; HLA Antigens/immunology ; HLA-B Antigens/immunology ; HLA-DR Antigens/immunology ; *Histocompatibility Testing ; Humans ; Isoantibodies/*blood/immunology ; Phenotype ; Republic of Korea

This report aims to investigate the dynamical changes of HBcAg18-27 epitope specific cytotoxic T lymphocytes(CTL), alanine aminotransferase (ALT), HBV DNA and HBsAg in peripheral blood of acute hepatitis B patients, and to explore the roles of HBcAg18-27-specific CTLs in virus clearance and liver injury. Acute hepatitis B (AHB) and chronic hepatitis B (CHB) patients were divided into two groups according to results of HLA-A0201. Patients with positive HLA-A0201 were classified into HBcAg-specific CTL group and those with negative HLA-A0201 were referred as control group. The specific CTLs were stained with HLA-A0201 limited HBcAg18-27 epitope MHC-Pentamer and the frequencies of CTLs, T, B, NK and NKT cells were detected by flow cytometry (FCM). The serum ALT, HBV DNA and HBsAg were examined using speed analysis, quantitative PCR and abbott chemiluminescent technology. The frequencies of HBcAg18-27-specific CTLs in AHB patients were higher in the early three weeks as compared to the late three weeks. The apex time of HBV-specific CTL frequencies lagged behind those of HBV DNA, HBsAg and ALT. The loss of HBsAg in patients with high frequencies of HBV-specific CTL was earlier than that in patients with low frequencies (t = 2.018, P value is less than 0.05). In the second week the peak frequencies of CD3+CD8+ cells overlapped with that of HBcAg18-27-specific CTLs and with a positive correlation between (r = 0.420, P value is less than 0.05). During the early stages of AHB, the frequencies of NK and NKT cells were found significantly lower than that of control group and CHB group and the levels were back to normal after recovery. Moreover, a negative correlation existed between the frequencies of NK cells and the dynamic changes of HBcAg18-27-specific CTLs (r = -0.435, P value is less than 0.01) in AHB group. The frequencies of HBcAg18-27-specific CTLs were significantly higher as compared to CHB group in the first three weeks (z = -3.258, -4.04, and -3.259, P value is less than 0.01). The early loss of HBsAg was closely related to the high frequencies of HBcAg18-27 specific CTLs in AHB patients. HBcAg-specific CTL frequencies in peripheral blood could be used to predict clinical outcome after HBV infection. The frequencies of CD8+ T cells can reflect the changes of frequencies of HBcAg-specific CTL during acute HBV infection.
Adolescent ; Adult ; Case-Control Studies ; Female ; HLA-A2 Antigen ; immunology ; Hepatitis B ; immunology ; Hepatitis B Core Antigens ; blood ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Lymphocyte Count ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Young Adult