High expression of MICA/B prolongs disease-free survival in patients with HER2positive breast cancer / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the relationship between expression of MICA/B (MHC class I chain-related proteinA/B) and disease-free survival (DFS) of patients with HER2+(human epidermal growth factor receptor 2) breast cancer tissue. Methods: Twenty six cases of corresponding para-cancerous tissue and 100 cases of HER2+ breast cancer tissue that preserved in wax at Zhengzhou People’ s Hospital Affiliated to Southern Medical University from January 2009 to June 2010 were collected for this study. Expression of MICA/ B in these tissue samples was detected by immunohistochemistry; and the relationship between MICA/B expression with clinicopathologic features as well as DFS was analyzed with Kaplan-Meier survival curve. Results: The expression of MICA/B in adjacent paracancerous tissues was negative (0/26), however, it was highly positive in cancer tissues (92/100), and the percentage with high expression was 65%(65/100), the difference was significant (P<0.05). High MICA/B expression rate in stage I was significantly higher than that in stage Ⅱ-Ⅲ (77.55% vs 52.94%， P<0.05), and the high expression rate in stage T1 was also significantly higher than that in stage T2-T4 (75.00% vs 52.27%， P<0.05). High MICA/B expression rate in ER+, PR+ group (with positive number≥1%) was significantly lower than that in ER- , PR-group (ER： 52.38% vs 74.14%，PR： 51.35% vs 73.02%， all P<0.05). MICA/B expression was correlated with clinical stages, the expression of ER, PR and tumor size (all P<0.05), but not associated with menopausal status, histological grade and lymph node metastasis (all P>0.05). Over-expression of MICA/B was closely associated with much better 6-year DFS rate in patients no matter with or without targeted therapy (the targeted group: 90.6% vs 72.2%; the untargeted group: 78.4% vs 58.8%, all P<0.05). Conclusion: Over-expression of MICA/B in HER2+ breast cancer tissue is closely related to DFS, which may be served as a potential prognosis indicator for patients with HER2+ breast cancer.

Research on polymorphism of MICA genes in patients with type 1 diabetes mellitus in the Han and Lipopulations in Hainan province / 中华检验医学杂志

Objective To investigate the genetic diversity of MICA, and to analyze the correlation between genetic polymorphisms of MICA and T1DM in population of Han and Li nationalities in Hainan province.Methods This study was performed as a case-control study.Fifty-five individuals with T1DM and Fifty-five healthy controls of Han and Li nationalities from Wuzhishan, Lingshui, Qiongzhong, Baisha, Ledong,Changjiang, Dongfang and Haikou regions in Hainan province(35 Male,20 Female of T1DM of Han;28 Male,27 Female of healthy controls of Han; 33 Male,22 Female of T1DM of Li; 28 Male, 27 Female of healthy controls of Li), were enrolled for the study.MICA allelic variation was analyzed by sequencing-based typing(PCR-SBT).Fisher′s exact test was performed to determine the statistical significance of the distribution and allele frequency of MICA.Results In healthy population,11 MICA-sequence and 5 MICA-STR alleles were found in Han nationality, while 13 MICA-sequence and 5 MICA-STR alleles were detected in Li nationality.The MICA-sequence allele MICA*008:01 and the MICA-STR allele MICA-A5 were most frequently observed in Han nationality[30.85%(29/94)and 41.49%(39/94), respectively],while MICA*002:01 and A4 were the most common in Li nationality[21.57%(22/102) and 36%(36/100), respectively].Among patients with T1DM, 10 MICA-sequence and 5 MICA-STR alleles were detected in Han, and 9 MICA-sequence and 5 MICA-STR alleles were found in Li.MICA*002:01 and A9 were most frequently observed in Han[29%(29/100),29.29%(29/99),respectively], while MICA*012:01, MICA*002:01 and the A4 were the most common in Li[21.15%(22/104), 21.15%(22/104),38.24%(39/102), respectively].The allelic frequency of MICA*002:01, MICA*010, MICA-A5, MICA-A6 and MICA-A9 between the healthy population and T 1DM patients of Han nationality(5.32%,22.34%,41.49 %,9.58%,6.38%, respectively in healthy population;29%,7%, 26.26%,2.02%,29.29%, respectively in T1DM patients), exist significant difference(χ2value were 18.799,9.233,5.218,5.197,16.762, respectively.P value were 0.000,0.002, 0.025,0.024,0.000, respectively.all P<0.05),while no significant difference(all P>0.05)between the healthy population and T1DM patients of Li nationality.Conclusions The most common MICA alleles were MICA*008:01 and MICA-A5 in healthy population of Han nationality, while MICA*002:01 and MICA-A4 in healthy population of Li nationality.MICA*002:01 and MICA-A9 were high frequency in T1DM patients of Han population,while the MICA*010,MICA-A5 and MICA-A6 were low frequency.There was not any MICA alleles associated with T1DM in Li nationality.

Lack of association between alopecia areata and HLA class I and II in a southeastern Brazilian population

Abstract: Background: Alopecia areata (AA) is a common disorder of unknown etiology that affects approximately 0.7% to 3.8% of patients among the general population. Currently, genetic and autoimmune factors are emphasized as etiopathogenic. Studies linking Human Leukocyte Antigens (HLA) to AA have suggested that immunogenetic factors may play a role in the disease's onset/development. Objectives: To investigate an association between AA and HLA class I/II in white Brazilians. Methods: Patients and control groups comprised 33 and 112 individuals, respectively. DNA extraction was performed by column method with BioPur kit. Allele's classification was undertaken using the PCR-SSO technique. HLA frequencies were obtained through direct counting and subjected to comparison by means of the chi-square test. Results: Most patients were aged over 16, with no familial history, and developed partial AA, with no recurrent episodes. Patients showed a higher frequency of HLA-B*40, HLA-B*45, HLA-B*53 and HLA-C*04 compared with controls, although P was not significant after Bonferroni correction. Regarding HLA class II, only HLA-DRB1*07 revealed statistical significance; nevertheless, it featured more prominently in controls than patients (P=0.04; Pc=0.52; OR=0.29; 95%; CI=0.07 to 1.25). P was not significant after Bonferroni correction. Conclusions: The development of AA does not seem to be associated with HLA in white Brazilians, nor with susceptibility or resistance. The studies were carried out in populations with little or no miscegenation, unlike the Brazilian population in general, which could explain the inconsistency found.

Vanilloid Receptor 1 Agonists, Capsaicin and Resiniferatoxin, Enhance MHC Class I-restricted Viral Antigen Presentation in Virus-infected Dendritic Cells

DCs, like the sensory neurons, express vanilloid receptor 1 (VR1). Here we demonstrate that the VR1 agonists, capsaicin (CP) and resiniferatoxin (RTX), enhance antiviral CTL responses by increasing MHC class I-restricted viral antigen presentation in dendritic cells (DCs). Bone marrow-derived DCs (BM-DCs) were infected with a recombinant vaccinia virus (VV) expressing OVA (VV-OVA), and then treated with CP or RTX. Both CP and RTX increased MHC class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Oral administration of CP or RTX significantly increased MHC class I-restricted OVA presentation by splenic and lymph node DCs in VV-OVA-infected mice, as assessed by directly measuring OVA peptide SIINFEKL-Kb complexes on the cell surface and by performing functional assays using OVA-specific CD8 T cells. Accordingly, oral administration of CP or RTX elicited potent OVA-specific CTL activity in VV-OVA-infected mice. The results from this study demonstrate that VR1 agonists enhance anti-viral CTL responses, as well as a neuro-immune connection in anti-viral immune responses.

Effect of matrix metalloproteinase-9 on the formation of soluble MICA protein in osteosarcoma cells / 实用医学杂志

Objective To provide a new putative target for immunotherapy on osteosarcoma and explore the effect of matrix metalloproteinase-9 (MMP-9) on the formation of soluble MICA protein in osteosarcoma cells. Methods MMP-9 antisense oligonucleotide was transfected to osteosarcoma cells with lipofectamine 2000. MMP-9 mRNA was assessed by RT-PCR. MMP-9 activity and soluble MICA (sMICA) in the culture supernatant was examined by zymography and quantified by ELISA, respectively. Results MMP-9 mRNA expression and gelatin enzymatic activity were inhibited in MMP-9 antisense oligonucleotide group. Comparing with the control group, lower concentration of sMICA was found in MMP-9 antisense oligonucleotide group (P = 0.011). Conclusion MMP-9 may have an effect on the formation of sMICA protein in osteosarcoma. MMP-9 could be regarded as a putative target for immunotherapy in osteosarcoma.

HLA among Brazilian patients with spontaneous chronic urticaria and positive autologous serum skin test / HLA em brasileiros com urticária crônica espontânea e teste cutâneo do soro autólogo positivo

BACKGROUND: An association between class I and II alleles of the major histocompatibility complex and idiopathic chronic urticaria has previously been observed in different populations, but there are still no studies on Brazilian populations in this regard. OBJECTIVE: The involvement of the major histocompatibility complex classes I and II (loci A, B and DR) in Brazilian patients with idiopathic chronic urticaria and a positive autologous serum skin test was investigated and compared with a healthy population group. METHODS: DNA was extracted from the blood of 42 patients with idiopathic chronic urticaria and major histocompatibility complex classes I and II alleles were determined using the polymerase chain reaction and a laboratory test for oligonucleotide hybridization using a single-filament probe. The frequencies of these alleles in patients with chronic urticaria were compared with the frequencies in 1000 genetically unrelated voluntary blood donors from the same region of Brazil. The diagnosis of idiopathic chronic urticaria was based on the patients' clinical history and routine laboratory tests. Only the patients with positive autologous serum skin test were selected. The allele distribution resulted from the patient and control groups were analyzed using odds ratios and 95% confidence intervals. RESULTS: No statistically significant differences were found between the positive autologous serum skin test patients with chronic urticaria and the control group. CONCLUSIONS: We found that in this population group, there was no specific association between the HLA alleles studied and chronic urticaria. We believe that further population studies are needed in order to investigate the possible existence of this association.

FUNDAMENTOS: A associação entre os alelos do MHC classe I e II e a urticária crônica idiopática tem sido previamente constatada em diferentes populações, sendo que na população brasileira ainda não existem estudos a este respeito. OBJETIVOS: Foi estudado o envolvimento do MHC classe I e II (locci A, B e DR) em pacientes brasileiros com urticária crônica idiopática e teste cutâneo do soro autólogo positivo, comparando-se com um grupo populacional saudável. MÉTODOS: O DNA foi extraído do sangue de 42 pacientes com urticária crônica idiopática e o MHC classe I e II determinado por reação em cadeia da polimerase e teste laboratorial de hibridização de oligonucleotídeo com sonda de filamento único. A freqüência destes alelos em pacientes com urticária crônica idiopática foi comparada com a de 1000 doadores de sangue voluntários e geneticamente não relacionados, da mesma região do Brasil. O diagnóstico de urticária crônica idiopática foi baseado na história clínica do paciente e exames laboratoriais de rotina; foram selecionados apenas os pacientes com teste cutâneo do soro autólogo positivo. O resultado da distribuição alélica entre o grupo de pacientes e o grupo controle foi analisado através do odds rate com o cálculo do intervalo de confiança de 95% (95% IC). RESULTADOS: Não foram encontradas diferenças com significância estatística entre os pacientes com urticária crônica teste cutâneo do soro autólogo positivos e o grupo controle. CONCLUSÕES: Verificamos que neste grupo populacional estudado não houve associação específica entre os alelos HLA estudados e a urticária crônica; acreditamos na necessidade de outros estudos populacionais, para podermos verificar a possível existência desta associação.

Prolonged expression of MHC class I - peptide expression in bone marrow derived retrovirus transfected matured dendritic cells by continuous centrifugation in the presence of IL-4.

Background & objectives: Dendritic cells (DCs) are potent antigen presenting cells which proceed from immature to a mature stage during their differentiation. There are several methods of obtaining long lasting mature antigen expressing DCs and different methods show different levels of antigen expressions. We investigated bone marrow derived DCs for the degree of maturation and genetically engineered antigen presentation in the presence of interleukin-4 (IL-4) as a maturity enhancer. Methods: DCs and transfected retrovirus were cultured together in the presence of granulocyte-macrophage colony stimulating factor (GMCSF)-IL4, GMCSF +IL4, lipopolysaccharide (LPS). B 7.1, B7.2 and CD11c were measured by the degree of immune fluorescence using enhanced green fluorescent protein (EGFP) shuttled retrovirus transfected antigen. Degree of MHC class I molecule with antigen presentation of antigen was also evaluated by fluorescence activated cell sorting. The antigen presenting capacity of transfected DCs was investigated. Bone marrow DCs were generated in the presence of GMCSF and IL-4 in vitro. Dividing bone marrow cells were infected with EGFP shuttled retrovirus expressing SSP2 by prolonged centrifugation for three consecutive days from day 5, 6 and 7 and continued to culture in the presence of GMSCF and IL-4 until day 8. Results: IL-4 as a cytokine increased the maturation of retrovirus transfected DCs by high expression of B 7-1 and B 7-2. Also, IL-4 induced DC enhanced by the prolonged centrifugation and it was shown by increased antigen presentation of these dendric cells as antigen presenting cell (APC). Cytolytic effects were significantly higher in cytotoxic T cell response (CTLs) mixed with transfected DCs than CTLs mixed with pulsed DCs. Interpretation & conclusions: There was an enhanced antigen presentation by prolonged expression of antigen loaded MHC class I receptors in DCs in the presence of IL-4 by prolonged centrifugation.

Correlation between serum anti-MICA antibodies and chronic rejection in renal transplant recipients / 中华器官移植杂志

Objective To explore the relationship of serum anti-MICA antibody and development of chronic rejection (CR) after renal transplantation. Methods The enrolled 105 patients included 43 cases of CR, and 62 cases of functioning renal allograft as controls. Data including PRA level before transplantation, HLA mismatch, cold ischemic time, SCr at discharge, immunosuppressive regimen,and months after transplantation were analyzed. Blood samples were collected immediately after grouping for anti-MICA antibodies, SCr determination. Acute rejection episodes and renal allograft function which was evaluated by △SCr/M [(SCr at present - SCr at discharge) /months after transplantation) were compared between anti-MICA-antibody positive patients and anti-MICA-antibody negative patients. Results There was no significant difference in gender, age, HLA mismatch, cold ischemic time, immunosuppressive regimen, SCr at discharge, months after transplantation between CR and control groups (P＞0.05). Serum creatinine level and number of antiMICA-antibody positive patients in CR group were significantly increased as compared with those in control group (P＜0.01 ). Acute rejection episodes during the first 3 months after transplantation in anti-MICA-antibody positive patients were significantly more than those in anti-MICA-antibody negative patients (P＜0.05),and the △SCr/M in the former was higher than that in the latter (8.3 +3.6 vs 2.4 ± 2.6, P＜0.05). Conclusion Humoral immunoreaction mediated by MICA partly participates the development of CR after renal transplantation. MICA antibody is a risk factor affecting long-term allograft function.

Expression of anti-MICA antibodies and its influence on acute rejection and allograft function of sensitized renal recipients in early post-transplant course / 中华器官移植杂志

Objective To explore the expression of anti-MICA antibodies and evaluate its influence on acute rejection and renal function in early period after renal transplantation. Methods A total of 29 sensitized subjects (PRA＞20 %) were enrolled in this study. All the patients underwent protein A immunoabsorption treatment and the expression of anti-MICA antibodies was detected before and after treatment. Triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil (MMF) and steroid was given to prevent graft rejection. The correlation between the expression of anti-MICA antibodies and acute rejection or serum creatinine (SCr) level was analyzed.Results The expression of anti-MICA antibodies was detected in 8 candidates (27. 6 % ,8/29) ,and 6 kinds of anti-MICA antibodies simultaneously expressed were found in one individual, 3 kinds in one case,and sole kind in 6 patients. There was no significant difference in acute rejection rate between positive anti-MICA antibodies group and negative group [37.5 % (3/8) vs 38. 1% (8/21), P＞0.05). The positive expression rate of anti-MICA antibodies in the recipients with PRA ≥40% was higher than that in those with PRA ＜40% [43. 8 % (7/16) vs 7. 7 % (1/13),P＜0.05]. The SCr level in patients positive for anti-MICA antibodies was markedly higher than that in those negative anti-MICA antibodies at the 1st week postoperatively ( 135.4 ± 21.4 vs 108. 6 -+ 31.6 μmol/L, P＜0.05). The SCr level in the patients with positive anti-MICA antibodies, however, was reduced to the normal range at the 2nd week after surgery (P＞0.05). The levels of anti-MICA antibodies were continuously decreased in the candidates undergoing protein A irnmunoadsorption treatment. Conclusion Higher expression of anti-MICA antibodies exists in sensitized recipients and possesses an influence on the recovery of renal function in early postoperative period. Protein A immunoadsorption can eliminate anti-MICA antibodies effectively in sensitized recipients.

Expression of MICA mRNA and Protein in Osteosarcoma / 中山大学学报(医学科学版)

[Objective] To investigate the expression of MICA mRNA and protein in osteosarcoma and give a more comprehensive understanding to its immune evasion.[Methods] RT-PCR was used to analyze MICA mRNA in 11 osteosarcoma tissues and 5 osteosarcoma cell lines.MICA expression was examined in 66 paraffin-embedded osteosarcoma tissues and 6 paraffin-embedded normal bone tissues by immunohistochemistry,and MICA protein in 9 fresh osteosarcoma tissues was detected by Western blot too.MICA surface expression was estimated by flow cytometry.[Results] Nine of eleven (81.8%) osteosarcoma specimens and all of the five cell lines consistently expressed MICA mRNA.Up-regulation of MICA expression was found in osteosarcoma (34/66,51.6%),compared with normal bone tissues (0/6,0%).The cell lines Saos-2,MG63,and HOS showed positive surface MICA expression,while the U2OS and OS732 showed very limited expression.[Conclusion] MICA mRNA and protein predominantly expressed on osteosarcoma tissues and cell lines.

Expression and correlation of NKG2D and sMICA in lung cancer patients / 肿瘤研究与临床

Objective To investigate the expression and correlation of NKG2D and sMICA in lung cancer patients. Methods By collecting 30 lung cancer patients as the test group,and taking 30 healthy volunteers as the contrast group, the expression of NKG2D and sMICA in the two groups were examined separately by FACS and ELISA method. Results The expressions of NKG2D in the two groups were (81.56±8.78) %, (85.63±6.62) %. The lung cancer patients were high remarkable. There was a significant difference between the two groups (P <0.05). The expression of sMICA in the two groups were (354.13 ±80.575) pg/ml,(216.53±48.175) pg/ml. The lung cancer patients were low remarkable. There was a significant difference between the two groups (P <0.01). There was a significant relation between the two groups (r =-0.349, P =0.006). Conclusion The expression of NKG2D and sMICA may provid one of the immune targets for diagnosing that can forecast the immune state and malignant metastasis of the lung cancer patients. The significant relation between NKG2D and sMICA may take on main role in the immune escaping of tumor. It may provide the suitable target of the patients for tumor organisms and immune treatment.

Down-regulation of MHC class I Expression in Porcine Aortic Endothelial Cells by Introduction of hCMV US Genes / 대한이식학회지

PURPOSE: Direct recognition of porcine MHC proteins by human T cells is an impediment to successful xenotransplantation. Therefore, reducing human T cell response initiated by the interaction between TCR/CD8 cell and MHC class I on pig endothelial cell may be beneficial in successful pig- to-human xenotransplantation. METHODS: We examined MHC expression on porcine endothelial cell line, MYP30 cells in the absence or presence of IFN-g by FACS analysis. We introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce MHC class I expression on the cell surface after infection, into MYP30 cells in order to test the feasibility of modifying these cells to reduced MHC class I antigens by the introduction of hCMV US genes such as US2, 3, 6 or 11. RESULTS: MHC class I expressions in MYP30 cells were dramatically induced by IFN-gamma treatment. FACS analysis showed that cells transfected with the hCMV US2, 3, 6 or 11 genes exhibited 30~40% of MHC class I expression compared with mock-transfected cells. We next established stable cell lines expressing US6 gene, which had been found to exert best down-regulation effect on MHC class I expression. Stable cell line expressing US6 gene products exhibited more than 10% reduced expression level of the MHC class I compared with transiently transfected cells. CONCLUSION: Although the further analysis of the cytotoxicities of T and NK cells on the hCMV US gene transfected cells are needed to clarify the feasibility of their application, these results suggest that virus stealth technology can be exploited for xenotransplantation.

Hepatitis B Virus DNA Mutation, Pattern of Major Histocompatibility Class-I among Familial Clustered HBV Carriers in Relation to Disease Progression / 예방의학회지

OBJECTIVES: Chronic HBsAg carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing serious liver diseases. In Korea, it has been estimated that 65-75% of the HBsAg positives remained as persistent carriers. Additionally, familial clustering of HBV infection has frequently been observed among carriers. Some would become progressive, chronic hepatitis patients, and others would not. The aim of this study was to evaluate the association between various factors, such as the duration of infection, type of virus, mutation of precore/core region in HBV, major histocompatibility class-I, and developing chronic liver diseases among familial HBV carriers. METHODS: Chronic carrier status was identified by repeated serological tests for HBsAg at intervals of six months or more. A familial chronic carrier was defined when the disease was observed in a family member over two generations. Two families were recruited, among which a total of 20 chronic HBsAg carriers(11 carriers in No.1, and 9 in No.2 family) were identified. Data on the general characteristics and liver disease status were collected. Identification of the HBV-DNA was successful only for 13 subjects among the 20 carriers. Analysis of viral DNA in terms of subtype, pre-core and core region mutations was carried out. The type of major histocompatibility class-I for the 13 subjects was also analysed. RESULTS & CONCLUSIONS: Seven of 10 chronic HBV carriers of the 1st generation and one of 10 of the 2nd generation were clinical patients with chronic hepatitis, the others, three of the 1st and nine of the 2nd generation, were asymptomatic carriers. This data indicates that the duration of HBV carriage is one of the major factors for disease severity. The subtype of HBsAg analysed using HBV-DNA identified in 13 carriers were adr, and the pattern of precore nonsense mutation in HBV-DNA was identical among family members, which means that the same virus strains were transmitted between the family members. The association between the precore or core mutations in HBV-DNA and the disease severity was not observed. While it was suggested that a specific type of MHC class-I may be related to disease progression.

Monophosphoryl lipid A (MPL) upregulates major histocompatibility complex (MHC) class I expression by increasing interferon-gamma (IFN-gamma)

Tumor immunity is primarily mediated by cells as CD8+ cytotoxic T lymphocytes (CTL) recognize tumor antigen by MHC class I molecules. But most tumors are associated with a decreased expression of MHC class I to escape the antitumor immunity of the host. Our previous data have demonstrated that MPL has an antitumor effect on metastatic lung cancer of B16 melanoma with enhancing cytotoxicity due to increase of IFN-gamma and IL-2, and decrease of IL-4, which indicates the stimulation of type 1 helper T cells (Th1). To determine the effects of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha on MHC class I expression of B16 melanoma cells, we evaluated the expression of MHC class I molecules with treatments of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha by flow cytometry. The supernatant of MPL-treated spleen cells in vitro upregulated the expression of MHC class I molecules of B16 melanoma cells compared to the control supernatant of spleen cells. The MHC class I expression of B16 melanoma cells treated with IFN-gamma, but not TNF-alpha or IL-1 alpha, increased in a time-dependent manner. In conclusion, MPL upregulated MHC class I expression of B16 melanoma cells by activating spleen cells via IFN-gamma. These data suggest that increased IFN-gamma by MPL is responsible for the upregulation of MHC class I expression to augment cytotoxicity. Therefore, we suggest that MPL could play an important role in immunotherapy.

Patogenia de las espondiloartropatías seronegativas

Se estudió la función que desempeña el antígeno leucocitario humano (HLA-B27) en la patogénesis de las espondiloartropatias seronegativas. Se describió detalladamente la zona de unión de péptidos de la molécula conocida como «bolsón 45». Como hipótesis actuales en el surgimiento de la enfermedad se discutieron la mímica molecular entre bacterias artritogénicas y HLA-B27, la positividad del HLA-B27 y la persistencia de las infecciones enterobacteriales, HLA-B27 factores modificantes y el modelo del péptido artritogénico. Se explicó la función de la célula T CDB+ en el desencadenamiento de la enfermedad y su control por los linfocitos T CD4+.

The function of HLA-B27 in the pathogenesis of seronegative spondyloarthropathies was studied. The zone of union of the peptides of the molecule known as «big pocket 45» was described in detail. The molecular mimicry between arthritogenic bacteria and HLA-B27, the positivity of HLA-B27 and the persistance of enterobacterial infections, the HLA-B27 modifying factors, and the model of arthritogenic peptide were discussed as present hypotheses connected with the appearance of the disease. The function of the CDB-positive T-cell in the outbreak of the disease, as well as its control by the CD4-positive T-lymphocytes was explained.

Partial purification and characterization of a novel murine factor that augments the expression of class I MHC antigens on tumor cells

A soluble factor which augments the expression of major histocompatibility complex class I (MHC I) antigens on a number of murine tumor cell lines, has been isolated from the culture supernatants of mixed lymphocyte reaction of spleen cells derived from C57B1/6, Balb/c and Swiss mice. The factor, termed MHC-augmenting factor (MHC-AF) has been partially purified by Sephadex G-100 column chromatography and reverse phase HPLC. MHC-AF activity is associated with an 18 kDa molecule. MHC-AF activity was resistant to pH 2.0 treatment and partially purified MHC-AF preparations did not have any activity in L929 cell/vesicular stomatitis virus (VSV) interferon bioassay system. Antibodies to IFN-gamma did not block the activity of MHC-AF. These results indicate that a MHC-AF distinct from IFN-gamma, is produced by mouse spleen cells undergoing a mixed lymphocyte reaction.

Expression of p53 and MHC Class I According to HPV Infection in Laryngeal Squamous Cell Carcinomas / 대한암학회지

PURPOSE: We evaluated the HPV type 16, 18 infection and p53 expression and MHC class Iantigen expression, and analyzed he relationship between HPV infection and p53 expression and MHC class I expression in laryngeal squamous cell carcinomas. MATERIALS AND METHODS: Thirty-nine cases of laryngeal squamous cell carcinomas and ten cases of laryngeal nodules were analyzed for detection of HPV DNA by in situ hybridization and the detection of p53 and MHC class I antigen by immunohistochemical technique. RESULTS: HPV DNA was detected in 10(26%), and p53 expression was detected in 19(49%) out of 39 cases in laryngeal squamous cell carcinomas. HPV positive cases showed 50% of p53 expression whereas HPV negative cases showed 48% expression. MHC class I down-regulation (heterogenous and negative expression) in HPV positive lesions was higher than HPV negative lesions, but there was no statistically significance. The expression of MHC class I was related to cellular differentiation regardless of T-stage and nodal involvement. CONCLUSION: There was no reiationship between HPV infection and p53 expression and MHC class I expression in laryngeal squamous cell carcinomas. Also these results suggest that MHC class I expression can make it possible to presume indirectly the malignant potentiality of the tumor.

Association of HLA-A Alleles with Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To explore the potential association of HLA-A alleles and genetic susceptibility with systemic lupus erythematosus (SLE). Methods Polymerase chain reaction-sequence specific primer (PCR-SSP) was used to analyze the distribution of HLA-A alleles among 106 patients with systemic lupus erythematosus and 122 healthy persons. Results Nineteen out of twenty-four kinds of HLA-A alleles were found from the specimens, including 18 kinds in SLE specimens, and 15 kinds in control specimens. Among them, HLA-A*11 allele was positively associated with SLE (RR = 2.4380, EF = 0.1502, ?2 = 12.2440, P = 0.0005, Pc = 0.0095). For A*01 and A*24, although the P values were less than 0.05, the Pc values were more than 0.05 (0.9462 or 0.2356, respectively). Conclusions The results indicate that HLA-A*11 may be the susceptible allele or may be closely linked with the susceptible genes in Chinese SLE patients.

The Roles of MHC Class I Molecule and ICAM-1 in the Induction of CTL by IL-2, IL-4 or IL-6 Gene-Transfected Tumor Vaccines / 中国肿瘤生物治疗杂志

In the present study, the expression of MHC class I molecule and ICAM - 1 on the surface of B16 melanoma cells were observed, and their roles in the induction of CTL were investigated. The results showed that both MHC class I and ICAM - 1 expression increased after IL-2, IL-4, or IL-6 gene transfection. The splenocyte CTL activity was enhanced significantly after in vivo immunization with cytokine gene - transfected B16 melanoma cells. The CTL induction was partly inhibited by anti-ICAM-1 mAb and was completely abolished by anti-MHC class I mAb. These results suggested the increased immunogenicity of IL-2,IL-4 or IL-6 gene-transfected B16 melanoma cells may be related to the upregula-tion of ICAM-1 or MHC class I molecules after cytokine gene transfection.

Impact of HBV/C gene mutation G87 on HIA-I expression of host cells / 解放军医学杂志

Objective To study the impact of HBV/C gene G87 mutation on HLA-I expression of host cells. Methods HBV wild-type genome plasmid was reconstructed by site-directed mutagenesis technique and subcloning technique into expression vector of G87 mutant (EBO-G87) and expression vector of wild type (EBO-WT), which were transfected into HepG2 cells via liposome technique,respectively.The transfected cells were stained with murine mAb anti-HLA-ABC conjugated directly to FITC, and HLA-I expression on their membranes was analyzed by flow cytometry. Results The constructed vectors of EBO-WT and EBO-G87 were identified by restriction enzyme digestion and nucleotide sequencing. The mean fluorescence intensity of HLA-I expression on transfected cells with EBO empty vector was at low level(2.3). It was elevated remarkably to 18.8 by EBO-WT, while that of EBO-G87 was increased to 10.5. Conclusion Two strains of HBV may up-regulate the expression of HLA-I, and G87 mutation of C gene may affect the expression level of HLA-I on host cells.