{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:06:57Z","timestamp":1781104017196,"version":"3.54.1"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,8,24]]},"abstract":"\n Proteins released from\n Mycobacterium tuberculosis<\/jats:italic>\n (\n Mtb<\/jats:italic>\n ) during late logarithmic growth phase are often considered candidate components of immunogenic or autolysis markers. One such protein is isocitrate dehydrogenase (ICD), a key regulatory enzyme in the citric acid cycle. We have evaluated the immunogenic properties of two isoforms of\n Mtb<\/jats:italic>\n ICD and compared them with the control antigens heat-shock protein 60 and purified protein derivative (PPD). PPD lacks the sensitivity to distinguish between bacillus Calmette\u2013Gu\u00e9rin (BCG)-vaccinated and tuberculosis (TB)-infected populations, and, therefore, epidemiological relevance of PPD in BCG-vaccinated regions is debatable. We show that\n Mtb<\/jats:italic>\n ICDs elicit a strong B cell response in TB-infected populations and can differentiate between healthy BCG-vaccinated populations and those with TB. The study population (\n n<\/jats:italic>\n = 215) was categorized into different groups, namely, patients with fresh infection (\n n<\/jats:italic>\n = 42), relapsed TB cases (\n n<\/jats:italic>\n = 32), patients with extrapulmonary TB (\n n<\/jats:italic>\n = 35), clinically healthy donors (\n n<\/jats:italic>\n = 44), nontuberculous mycobacteria patients (\n n<\/jats:italic>\n = 30), and non-TB patients (culture negative for acid-fast bacteria but carrying other infections,\n n<\/jats:italic>\n = 32). The\n Mtb<\/jats:italic>\n ICDs showed statistically significant antigenic distinction between healthy BCG-vaccinated controls and TB patients (\n P<\/jats:italic>\n < 0.0001) and those with other infections. Although extrapulmonary infections could not be discriminated from healthy controls by heat-shock protein 60 (\n P<\/jats:italic>\n = 0.2177), interestingly, the\n Mtb<\/jats:italic>\n ICDs could significantly (\n P<\/jats:italic>\n < 0.0001) do so. Our results highlight the immunodominant, immunosensitive, and immunospecific nature of\n Mtb<\/jats:italic>\n ICDs and point to an unusual property of this tricarboxylic acid energy cycle enzyme.\n <\/jats:p>","DOI":"10.1073\/pnas.0404347101","type":"journal-article","created":{"date-parts":[[2004,8,16]],"date-time":"2004-08-16T21:08:46Z","timestamp":1092690526000},"page":"12652-12657","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["Mycobacterium tuberculosis<\/i>\n (\n Mtb<\/i>\n ) isocitrate dehydrogenases show strong B cell response and distinguish vaccinated controls from TB patients"],"prefix":"10.1073","volume":"101","author":[{"given":"Sharmistha","family":"Banerjee","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500076, India; Laboratory of Microbiology, Central JALMA Institute for Leprosy, Agra 282001, India; Mahavir Hospital and Research Centre, Hyderabad 500004 India; and Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Nandyala","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500076, India; Laboratory of Microbiology, Central JALMA Institute for Leprosy, Agra 282001, India; Mahavir Hospital and Research Centre, Hyderabad 500004 India; and Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raviprasad","family":"Podili","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500076, India; Laboratory of Microbiology, Central JALMA Institute for Leprosy, Agra 282001, India; Mahavir Hospital and Research Centre, Hyderabad 500004 India; and Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. M.","family":"Katoch","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500076, India; Laboratory of Microbiology, Central JALMA Institute for Leprosy, Agra 282001, India; Mahavir Hospital and Research Centre, Hyderabad 500004 India; and Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. J. R.","family":"Murthy","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500076, India; Laboratory of Microbiology, Central JALMA Institute for Leprosy, Agra 282001, India; Mahavir Hospital and Research Centre, Hyderabad 500004 India; and Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed E.","family":"Hasnain","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500076, India; Laboratory of Microbiology, Central JALMA Institute for Leprosy, Agra 282001, India; Mahavir Hospital and Research Centre, Hyderabad 500004 India; and Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,8,16]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.7.677"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1055"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000078312"},{"key":"e_1_3_2_4_2","first-page":"1123","volume":"289","year":"2000","unstructured":"Helmuth, L. (2000) Science 289, 1123\u20131125.10970221","journal-title":"Science"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/339818"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.2.443-450.2002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.4.1712-1716.2003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.7.3240-3247.2004"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/170.5.1326"},{"key":"e_1_3_2_10_2","unstructured":"Laidlaw M. (1989) in Practical Medical Microbiology eds. Colle J. G. Duguid J. P. Fraser A. G. & Marimon B P. (Churchill Livingstone New York) pp. 399\u2013416."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1530"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(02)00048-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365540110026971"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2003.12.015"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200402-179OC"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.6.1905-1910.1991"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8479(96)90120-3"},{"key":"e_1_3_2_18_2","first-page":"846","volume":"9","year":"2002","unstructured":"Florio, W., Bottai, D., Batoni, G., Esin, S., Pardini, M., Maisetta, G. & Campa, M. (2002) Clin. Diagn. Lab. Immunol. 9, 846\u2013851.12093684","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000071701.62486.49"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_3_2_21_2","unstructured":"Saiman L. (2004) Paediatr. Respir. Rev. 221\u2013223."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.11.2459"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2003.07.014"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268803001535"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.11.6338-6343.2003"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365540310000292"},{"key":"e_1_3_2_27_2","first-page":"165","volume":"53","year":"2003","unstructured":"Brusasca, P. N., Peters, R. L., Motzel, S. L., Klein, H. J. & Gennaro, M. L. (2003) Comp. Med. 53, 165\u2013172.12784850","journal-title":"Comp. Med."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.3.1322-1325.2003"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.123.1.107"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.10.3603-3608.2001"},{"key":"e_1_3_2_31_2","unstructured":"Chakhaiyar P. Nagalakshmi Y. Aruna B. Murthy K. J. R Katoch V. M. & Hasnain S. E. (2004) J. Infect. Dis. in press."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0404347101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:15:27Z","timestamp":1649754927000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0404347101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8,16]]},"references-count":31,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2004,8,24]]}},"alternative-id":["10.1073\/pnas.0404347101"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0404347101","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1088686.542794","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8,16]]},"assertion":[{"value":"2004-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-08-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}