{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:46:51Z","timestamp":1780440411213,"version":"3.54.1"},"reference-count":74,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,4,21]],"date-time":"2012-04-21T00:00:00Z","timestamp":1334966400000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>Purified protein derivative (<jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content>) has served as a safe and effective diagnostic reagent for 60 years and is the only broadly available material to diagnose latent tuberculosis infections. This reagent is also used as a standard control for a number of in vitro immunological assays. Nevertheless, the molecular composition and specific products that contribute to the extraordinary immunological reactivity of <jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content> are poorly defined. Here, a proteomic approach was applied to elucidate the gene products in the <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>ood and <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>rug <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>dministration (<jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content>) standard <jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>2. Many known <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ycobacterium tuberculosis<\/jats:italic> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell antigens were detected. Of significance, four heat shock proteins (<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>s) (GroES, GroEL2, HspX, and DnaK) dominated the composition of <jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content>. The chaperone activities and capacity of these proteins to influence immunological responses may explain the exquisite solubility and immunological potency of <jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content>. Spectral counting analysis of three separate <jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content> reagents revealed significant quantitative variances. Gross delayed\u2010type hypersensitivity (<jats:styled-content style=\"fixed-case\">DTH<\/jats:styled-content>) responses in <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>. tuberculosis<\/jats:italic> infected guinea pigs were comparable among these <jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content> preparations; however, detailed histopathology of the <jats:styled-content style=\"fixed-case\">DTH<\/jats:styled-content> lesions exposed unique differences, which may be explained by the variability observed in the presence and abundance of early secretory system (<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>sx) proteins. Variability in <jats:styled-content style=\"fixed-case\">PPD<\/jats:styled-content> reagents may explain differences in <jats:styled-content style=\"fixed-case\">DTH<\/jats:styled-content> responses reported among populations.<\/jats:p>","DOI":"10.1002\/pmic.201100544","type":"journal-article","created":{"date-parts":[[2012,4,21]],"date-time":"2012-04-21T11:01:11Z","timestamp":1335006071000},"page":"979-991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Deciphering the proteome of the in vivo diagnostic reagent \u201cpurified protein derivative\u201d from <i><scp>M<\/scp>ycobacterium tuberculosis<\/i>"],"prefix":"10.1002","volume":"12","author":[{"given":"Yun Sang","family":"Cho","sequence":"first","affiliation":[{"name":"Mycobacteria Research Laboratories Department of Microbiology, Immunology, and Pathology Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Dobos","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories Department of Microbiology, Immunology, and Pathology Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Prenni","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Facility Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Yang","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories Department of Microbiology, Immunology, and Pathology Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Statistics Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Rosenkrands","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology Statens Serum Institut  Copenhagen S Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology Statens Serum Institut  Copenhagen S Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Weon","family":"Ryoo","sequence":"additional","affiliation":[{"name":"Korea Institute of Tuberculosis  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gill\u2010Han","family":"Bai","sequence":"additional","affiliation":[{"name":"Korea Institute of Tuberculosis  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology Center for Biologics Evaluation and Research, Food and Drug Administration  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Izzo","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories Department of Microbiology, Immunology, and Pathology Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helle","family":"Bielefeldt\u2010Ohmann","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories Department of Microbiology, Immunology, and Pathology Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Belisle","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories Department of Microbiology, Immunology, and Pathology Colorado State University  Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1206810"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1909.25420350001001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.63.1642.619c"},{"key":"e_1_2_7_5_1","first-page":"9","article-title":"Tuberculin purified protein derivative. Preparation and analysis of a large quantity for standard","volume":"44","author":"Seibert F. B.","year":"1941","journal-title":"Am. Rev. Tubercul."},{"key":"e_1_2_7_6_1","first-page":"161","article-title":"A comparison in the United States of America of two tuberculins, PPD\u2010S and RT23","volume":"31","author":"Comstock G. W.","year":"1964","journal-title":"Bull. World Health Organ."},{"key":"e_1_2_7_7_1","first-page":"845","article-title":"Standardization of a new batch of purified tuberculin (PPD) intended for international use","volume":"19","author":"Guld J.","year":"1958","journal-title":"Bull. World Health Organ."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.4.9906050"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/315677"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1999.00630.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1016\/S0021-9258(19)41636-0","article-title":"Purification and properties of tuberculin\u2010active protein from Mycobacterium tuberculosis","volume":"250","author":"Kuwabara S.","year":"1975","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/S0021-9258(19)41637-2","article-title":"Amino\u2010acid sequence of tuberculin\u2010active protein from Mycobacterium tuberculosis","volume":"250","author":"Kuwabara S.","year":"1975","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200600853"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-04-0329"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2683(20000301)21:5<935::AID-ELPS935>3.0.CO;2-P"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9709"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-146-12-3205"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(03)00179-5"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.11.012"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01549.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2683(200108)22:14<2936::AID-ELPS2936>3.0.CO;2-S"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27518-0"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02779.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.8.2672-2676.2001"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2005.10.002"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5777-5785.2001"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.13.3485-3491.2002"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27284-0"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.327-336.1999"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.15.4484-4492.1996"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/1615-9861(200104)1:4<574::AID-PROT574>3.0.CO;2-8"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200700528"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3547-3558.2005"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1086\/314438"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M600089-MCP200"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2004.1430.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/31159"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/85686"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2675315"},{"key":"e_1_2_7_40_1","first-page":"161","article-title":"MASCOT: multiple alignment system for protein sequences based on three\u2010way dynamic programming","volume":"9","author":"Hirosawa M.","year":"1993","journal-title":"Comput. Appl. Biosci."},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/10890"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606379103"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/13690"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-169-8:455"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.5.2066-2074.1992"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1995.1070"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp964"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606379103"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900437"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900836"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-5418-5_1"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr990076h"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac0341261"},{"key":"e_1_2_7_54_1","volume-title":"The Proteome of Mycobacterium Tuberculosis","author":"Belisle J. T.","year":"2005"},{"key":"e_1_2_7_55_1","volume-title":"Proteomics of Mycobacterium Tuberculosis","author":"Dobos K. M.","year":"2008"},{"key":"e_1_2_7_56_1","doi-asserted-by":"crossref","unstructured":"Vita R. Zarebski L. Greenbaum J. A. Emami H. Hoof I. et al. The immune epitope database 2.0.Nucleic Acids Res. 2010 38 D854--D862.","DOI":"10.1093\/nar\/gkp1004"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.11.014"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.210391497"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1086\/338149"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.07.103"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3301-3306.2005"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00943.x"},{"key":"e_1_2_7_63_1","first-page":"946","article-title":"Tuberculin PPD RT23 is stable: quality control data cannot be denied","volume":"2","author":"Haslov K.","year":"1998","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"e_1_2_7_64_1","first-page":"793","article-title":"Tuberculin PPD RT23: still going strong","volume":"2","author":"Haslov K.","year":"1998","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"e_1_2_7_65_1","first-page":"80","article-title":"Antigens of PPD, old tuberculin, and autoclaved Mycobacterium bovis BCG studied by crossed immunoelectrophoresis","volume":"124","author":"Harboe M.","year":"1981","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2009.07.003"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500061-MCP200"},{"key":"e_1_2_7_68_1","first-page":"S182","article-title":"New diagnostic tools for tuberculosis","volume":"4","author":"Perkins M. D.","year":"2000","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0019-2805.2004.01839.x"},{"key":"e_1_2_7_70_1","first-page":"1192","article-title":"False\u2010positive tuberculin skin tests: what is the absolute effect of BCG and non\u2010tuberculous mycobacteria?","volume":"10","author":"Farhat M.","year":"2006","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133515"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.4.2035"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.8.5130"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2005.08.014"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00486-10"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpmic.201100544","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.201100544","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:21:26Z","timestamp":1761049286000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pmic.201100544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4]]},"references-count":74,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1002\/pmic.201100544"],"URL":"https:\/\/doi.org\/10.1002\/pmic.201100544","archive":["Portico"],"relation":{},"ISSN":["1615-9853","1615-9861"],"issn-type":[{"value":"1615-9853","type":"print"},{"value":"1615-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4]]},"assertion":[{"value":"2011-10-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-01-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}