위암 세포주에서 C-erbB-2 (HER2/neu) 암유전자 과표현에 따른 NK 세포독성능의 효과와 IFN-γ 의 영향

허윤경,정노팔 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.2

The effect of c-erbB-2 overexpression in several stomach cancer cell lines on the cytotoxicity of NK cell was examined. C-erbB-2 overexpressed cell lines showed a resistance to NK cytotoxicity, when compared with the nonoverexpressed cell lines. IFN-y treatment reduced the level of c-erbB-2 on the surface of WDK, LJH and KHH cell lines, and the cytotoxicity was in-creased. On the other hand, ICAM-1 expression was increased in both c-erbB-2 overexpressed and nonoverexpressed cell lines by IFN-y. The NK cytotoxicity of c-erbB-2 nonoverexpressed JBH and KATOIII cell lines was reduced upon IFN-y treatment, but c-erbB-2 overexpressed WDK, LJH and KHH cell lines showed an increased NK cytotoxicity. Thus, the inhibition of the c-erbB-2 expression on the surface of target cell by IFN-y leads to increase in the susceptibility to NK cell. These results suggest that overexpression of c-erbB-2 oncogene in human stomach cancer cell lines may be involved in a resistance to NK cytotoxicity.

Evaluation of Antigen-Specific Immunoglobulin G Responses in Pulmonary Tuberculosis Patients and Contacts

Hur, Yun-Gyoung,Kim, Ahreum,Kang, Young Ae,Kim, An Sik,Kim, Dae Yeon,Kim, Yeun,Kim, Youngmi,Lee, Hyeyoung,Cho, Sang-Nae American Society for Microbiology 2015 Journal of clinical microbiology Vol.53 No.3

<P>This study aimed to evaluate the serodiagnostic potential of immunoglobulin G (IgG) responses to <I>Mycobacterium tuberculosis</I> antigens in pulmonary tuberculosis (TB) patients, recent TB contacts with latent TB infection (LTBI), and healthy subjects. Infections were assessed using tuberculin skin tests, QuantiFERON-TB Gold In-Tube tests, drug susceptibility testing, and molecular genotyping of clinical isolates. Serum IgG responses to selective <I>M. tuberculosis</I> antigens, including the 38-kDa and 16-kDa antigens, lipoarabinomannan (LAM), and recombinant early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10), were determined. We found that the serum IgG responses to all antigens might differentiate between active TB and LTBI, with LAM having the highest diagnostic value (area under the curve [AUC] of 0.7756, <I>P</I> < 0.001). Recurrent TB cases showed significantly higher IgG responses to 38 kDa, CFP-10 (<I>P</I> < 0.01), and LAM (<I>P</I> < 0.05) than new cases, and male patients had higher levels of antigen-specific IgG than females (<I>P</I> < 0.05). Conversely, drug resistance and patient body mass index did not affect IgG responses (<I>P</I> > 0.05). LAM-specific IgG responses differentiated between acid-fast bacillus (AFB) smear-positive and -negative patients (<I>P</I> < 0.01), whereas antigen-specific IgG responses did not vary with the <I>M. tuberculosis</I> genotype (<I>P</I> > 0.05). Significantly higher IgG responses to 38 kDa and 16 kDa were observed in AFB smear-negative patients than in controls. These results suggest that assessment of serum IgG responses to selective purified <I>M. tuberculosis</I> antigens may help improve the diagnosis of active TB, particularly for sputum smear-negative patients or recurrent cases, and these may also help to differentiate between active TB and LTBI.</P>

Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

Jeong, Yun Hee,Hur, Yun-Gyoung,Lee, Hyejon,Kim, Sunghyun,Cho, Jang-Eun,Chang, Jun,Shin, Sung Jae,Lee, Hyeyoung,Kang, Young Ae,Cho, Sang-Nae,Ha, Sang-Jun American Society for Microbiology 2015 Journal of clinical microbiology Vol.53 No.2

<P><I>Mycobacterium tuberculosis</I> is the major causative agent of tuberculosis (TB). The gamma interferon (IFN-γ) release assay (IGRA) has been widely used to diagnose TB by testing cell-mediated immune responses but has no capacity for distinguishing between active TB and latent TB infection (LTBI). This study aims to identify a parameter that will help to discriminate active TB and LTBI. Whole-blood samples from 33 active TB patients, 20 individuals with LTBI, and 26 non-TB controls were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and plasma samples were analyzed for interleukin-2 (IL-2), IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNF-α), IFN-γ, monokine induced by IFN-γ (MIG), interferon gamma inducible protein 10 (IP-10), interferon-inducible T cell alpha chemoattractant (I-TAC), and monocyte chemoattractant protein 1 (MCP-1) by using a commercial cytometric bead array. The <I>Mycobacterium tuberculosis</I> antigen-specific production of most of the assayed cytokines and chemokines was higher in the active TB than in the LTBI group. The mitogen-induced responses were lower in the active TB than in the LTBI group. When the ratio of TB-specific to mitogen-induced responses was calculated, IL-2, IL-6, IL-10, IL-13, TNF-α, IFN-γ, MIG, and IP-10 were more useful in discriminating active TB from LTBI. In particular, most patients showed higher IP-10 production to <I>Mycobacterium tuberculosis</I> antigens than to mitogen at the individual level, and the ratio for IP-10 was the strongest indicator of active infection versus LTBI with 93.9% sensitivity and 90% specificity. In conclusion, the ratio of the TB-specific to the mitogen-induced IP-10 responses showed the most promising accuracy for discriminating active TB versus LTBI and should be further studied to determine whether it can serve as a biomarker that might help clinicians administer appropriate treatments.</P>

Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from <i>Mycobacterium tuberculosis</i> Beijing/K Strain in Mice

Kim, Ahreum,Hur, Yun-Gyoung,Gu, Sunwha,Cho, Sang-Nae AMERICAN SOCIETY FOR MICROBIOLOGY 2017 CLINICAL AND VACCINE IMMUNOLOGY Vol.24 No.11

<P>The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guerin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tuberculosis-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (P < 0.05) and recalled gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-6, and IL-17 responses (P < 0.05 or P < 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log(10) reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4(+) T cells producing protective cytokines, such as IFN-gamma and IL-17, in lungs and spleens (P < 0.01) and CD4(+) multifunctional T cells producing IFN-gamma, tumor necrosis factor alpha (TNF-alpha), and/or IL-17 (P < 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN-gamma production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses in vivo, may be informative for vaccine development, particularly in regions where the M. tuberculosis Beijing/K-strain is frequently isolated from TB patients.</P>

Cytokine signatures in response to K-strain specific-antigens

( Kwang Joo Park ),( Yun Gyoung Hur ),( Ahreum Kim ),( Sang Nae Cho ),( Wou Young Chung ),( Young Sun Kim ),( Keu Sung Lee ),( Joo Hun Park ),( Seung Soo Shin ) 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.-

BACKGROUND: More than 70% of Mycobacterium tuberculosis (M. tb) strains reported in Korean patients showed the Beijing genotypes and K family strains of M. tb were identified as a highly transmissible predominant Beijing strain found in school outbreaks and about 40% of relapse cases. Analysis of immune signatures based on M. tb strains may help in identifying potential biomarkers for TB diagnostics in regions where the strain is endemic. Methods: A total of 52 pulmonary TB patients at diagnosis and 96 normal healthy subjects were recruited. Normal healthy subjects were defined as a group of latent TB infection (LTBI) or control based on the results of QuantiFERON-TB Gold In-Tube tests. Blood samples were obtained for diluted whole blood assays and multiplex bead arrays to determine antigen-specific immune responses. Results: MTBK_24800-specific interferon (IFN)-γ and CXCL10 (IP-10) responses discriminated the infected groups from the uninfected control group (AUC, 0.71; P<0.001). However, both IFN-γ and IP-10 did not differ between LTBI and TB, which is the same as ESAT-6 and CFP-10-specific responses. MTBK_24790 and MTBK_24800 induced significantly higher TNF-α responses in TB patients compared with the individuals with LTBI (AUC, 0.82 and 0.79, respectively; P<0.001) whereas ESAT-6 and CFP-10-specific TNF-α did not vary between LTBI and TB. Conclusions: Simultaneous measurement of MTBK_24800-specific IFN-γ, IP-10 and TNF-α may serve as an informative signature for diagnosis of TB and LTBI, particularly in regions where Beijing strain of M. tb is endemic.

Comparison of QFT-plus and QFT-GIT tests in immunocompetent patients

( Ji Young Hong ),( So Yeong Park ),( Myung Goo Lee ),( Chang Youl Lee ),( Youlim Kim ),( Yun-gyoung Hur ) 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-

Introduction: A new generation of QFT assay, Quantiferon-TB Gold Plus (QFT-Plus) has been recently developed. It includes an additional TB2 antigen tube which has peptides for stimulation of CD8+ T cells. This study evaluated the diagnostic performance of QFT-Plus and it was compared to that of QFT-GIT. Method: QFT-Plus test was performed in 33 patients with active tuberculosis (TB), 30 subjects with latent TB infection (LTBI) and 27 healthy controls. Results: A substantial agreement was observed between the outcomes of QFT-GIT and QFT-Plus tests. The concordance was 91.1% (kappa value 0.8). Of 8 discordant results, 5 (5.56%) and 3 (3.3%) were positive in QFT-GIT alone and QFT-Plus alone. Reactivity in the TB2 tube contributes to the difference between QFT-GIT and QFT-Plus. The median IFN-r production in TB1 and TB2 is significantly higher in a group of TB than LTBI (TB1, TB: 10.0 IU/ml, LTBI: 3.485 IU/ml, P=0.006. TB2, TB: 10.0 IU/ml, LTBI: 3.850 IU/ml, P=0.001). QTF-Plus showed significantly lower IFN-r concentrations compared to those obtained QFT-GIT in LTBI subjects (QFT-Plus: 3.850 IU/ml QFT-GIT: 7.205 IU/ml). However, the QFT-Plus test also did not discriminate between active TB and LTBI as shown in QFT-GIT. Conclusions: QFT-Plus and QFT-GIT tests showed a substantial agreement and similar accuracy for diagnosis of TB infection in immunocompetent patients. Further studies in a larger sample size are needed to evaluate the clinical significance of the QFT-Plus including CD8+ T cell epitopes.