IGRA検査の理論と検査技術について

1 IGRA T- .TB 25 5 25 1. 2. T- .TB 1. PPD BCG BCG M. tuberculosis M. bovis PNAS, 100, p7877-7882, 2003 2. PPD 3. 2 4. PPD BCG BCG ESAT-6 1995 P. Andersen T IFN-g ESAT-6 (the early secreted antigenic target 6 kDa protein) P. Andersen et al. Recall of long-lived immunity to Mycobacterium tuberculosis infection in mice. J. Immunol., Vol.

2 154, p3359, 1995. A. L Sorensen et al. Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis. Infection and Immunity, Vol. 63, p1710, 1995. 1996 ESAT-6 M. bovis BCG RD1 CFP-10 CFP-10 (10 kDa culture filtrate protein) Berthet, et al. A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology, Vol. 144, p3195, 1998. Skjot, et al. Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens. Infect. Immun., Vol 68, p214, 2000. ESAT-6/CFP-10 Tuberculosis complex Environmental strains M. tuberculosis M. kansasii M.

3 Africanum M. marinum M. bovis M. szulgai M. flavescens M. gastri ESAT-6/CFP-10 BCG substrains Gothenburg Moreau Tice Tokyo Danish Glaxo Montreal Pasteur Environmental strains M. avium M. intracellulare etc ESAT-6/CFP-10 BCG MAC T IFN-g T IFN-g BCG Interferon-Gamma Release Assays (IGRA) ESAT-6, CFP-10 1. - 1. - - 1.

4 2. T- .TB T- .TB T- .TB Interferon-Gamma Release Assays - QFT QuantiFERON -TB Gold ( )(QFT-Gold In-Tube) 15 .IFN-g 4 . 1mL 37 C 16-24 Stage 1: ESAT-6+CFP-10+ 2:IFN-gELISA ELISA IFN-g T- . TB(ELISPOT) ESAT-6/CFP-10 Y Y Y PBMCs PBMCs Y Y YY Y YELISPOT 2 IFN-g Nil Panel A Panel B Mitogen Nil Panel A Panel B Mitogen T- .TB 1 1 6 T- .TB 1 5mL) T- .TB T-Cell Xtend 32 QFT RD1 (ESAT-6 CFP-10) T 100 BCG QFT 32 PBMCs IFN- PBMCs PBMCs PBMCs IGRA IGRA T- IGRA T.

5 TB QFT-3G Detjen et al Clin Infect Dis (2007) (26/28) (26/28) Dominguez et al Clin Vacc Immunol (2008) (36/39) (33/39) Goletti et al. PLoS ONE. (2008) (58/69) (52/69) Chee et al., J Clin Microbiol (2008) (254/270) 83% (224/270) (374/406) (335/406) IGRA IGRA T- .TB QFT-3G Higuchi et al IJTLD (2012) (110/111) (96/97) Mancuso et al AJRCCM (2011) (1336/1354) (1338/1354) Total (1446/1465) (1434/1451) 1. Born in TB endemic countries. 2. Live in cities where TB incidences are more than 25 per 100,000. 3. Have lived more than 1 month in cities of foreign countries where TB is endemic. 4. Have abnormal chest X-ray observations.

6 5. Have had contact with TB patients. 6. Have TB patients among family members, friends, or acquaintances. 7. Have experiences working in places where TB infection is thought to be more likely, such as hospitals, prisons, the Self-Defense Forces, nursing homes, rehabilitation facilities, etc. Exclusion criteria of Healthy subjects Higuchi et al IJTLD (2012) T- .TB CDC 10 8 10 5 6 7 10 4 10 10 5 20 T- .TB -1 1 [ A ].. [ B ].. 2 1 6 5 10 20 T PHA 20 A B T.

7 TB -2 1. 5 7 8 5 10 8 10 6 7 10 5 10 4 10 10 5 20 T- .TB -3 QFT-3G T- .TB n % n % Specificity 110/111 110/111 QFT-3G IU/ml IU/ml T- 6 spots 5 spots QFT-3G T- .TB -1 QFT-3G T- .TB n % n % Specificity 96/111 110/111 QFT-3G T- .TB -2 QFT-IT IU/ml IU/ml IU/ml T.

8 TB 8 spots 5-7 spots 4 spot p = 120 116 HIV 95 Richeldi et al Chest 2009 T- .TB QFT-3G 13/369 ( ) 27/369 ( ) T- .TB QFT-3G ; QFT-3G T- .TB QFT-3G T- .TB QFT-3G 4 Bergamini et al Pediatrics 2009 T- .TB QFT-3G Other papers of interest: Ferrara et al Lancet 2006, Kobashi et al Scand J Inf Dis 2008, Kobashi et al Int Med 2009, Chung et al J Infect 2010 IGRA 496 (0-19 , 11 ) 1 2 IGRA HIV-1 , QFT-3G T.

9 TB CD4 128 HIV T- .TB QFT-IT IGRA Leidl et al., ERJ (2009) HIV HIV - 42/49 ( ) QFT-3G 13/19 ( ) 74/109 ( ) T- .TB 17/19 ( ) 59/109 ( ) HIV CD4 : QFT IFN- T- .TB CD4 T-Cell Xtend 60/62: 95%CI; 1 T-Cell Xtend T- .TB QFT IGRA T- .TB T- .TB T- .TB T- .TB 32 Research Institute of Immune Diagnosis (RIID) 238 190-0013 1-34-1 301 TEL: 042-595-8868 FAX: 042-595-8867 URL: E-mail: RIID