{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:33:07Z","timestamp":1777545187709,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several serological diagnostics rely on enzyme-linked immunosorbent assay (ELISA) to detect bacterial infections. However, for some pathogens, including Bartonella henselae, diagnosis still depends on manually intensive, time-consuming assays including micro-immunofluorescence, Western blotting or indirect immunofluorescence. For such pathogens, there is obviously still a need to identify antigens to establish a reliable, fast and high-throughput assay (Dupon et al. 8). We evaluated two B. henselae proteins to develop a novel serological ELISA: a well-known antigen, the 17-kDa protein, and GroEL, identified during this study by a proteomic approach. When serum IgG were tested, the specificity and sensitivity were 76 and 65\u00b77% for 17-kDa, respectively, and 82 and 42\u00b79% for GroEL, respectively. IgM were found to be more sensitive and specific for both proteins: 17-kDa protein, specificity 86\u00b72% and sensitivity 75%; GroEL, specificity 97\u00b77% and sensitivity 45\u00b73%. IgM antibodies were also measured in lymphoma patients and patients with Mycobacterium tuberculosis infection to assess the usefulness of our ELISA to distinguish them from B. henselae infected patients. The resulting specificities were 89\u00b71 and 93\u00b75% for 17-kDa protein and GroEL, respectively. Combining the results from the two tests, we obtained a sensitivity of 82\u00b78% and a specificity of 83\u00b79%. Our work described and validated a proteomic approach suitable to identify immunogenic proteins useful for developing a serological test of B. henselae infection.<\/jats:p><jats:sec><jats:title>Significance and Impact of the Study<\/jats:title><jats:p>A reliable serological assay for the diagnosis of Cat Scratch Disease (CSD) \u2013 a pathological condition caused by Bartonella henselae infection \u2013 has not yet been developed. Such an assay would be extremely useful to discriminate between CSD and other pathologies with similar symptoms but different aetiologies, for example lymphoma or tuberculosis. We investigate the use of two B. henselae proteins \u2013 GroEL and 17-kDa \u2013 to develop a serological-based ELISA, showing promising results with the potential for further development as an effective tool for the differential diagnosing of B. henselae infection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/lam.12286","type":"journal-article","created":{"date-parts":[[2014,5,17]],"date-time":"2014-05-17T05:54:40Z","timestamp":1400306080000},"page":"253-262","source":"Crossref","is-referenced-by-count":9,"title":["Development of an enzyme-linked immunosorbent assay for<i>Bartonella henselae<\/i>infection detection"],"prefix":"10.1093","volume":"59","author":[{"given":"F.","family":"Ferrara","sequence":"first","affiliation":[{"name":"New Mexico Consortium Los Alamos NM USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Di Niro","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"D'Angelo","sequence":"additional","affiliation":[{"name":"New Mexico Consortium Los Alamos NM USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Busetti","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health \u2013 IRCCS \u201cBurlo Garofolo\u201d Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Marzari","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Trieste Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Not","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health \u2013 IRCCS \u201cBurlo Garofolo\u201d Trieste Italy"},{"name":"University of Trieste Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Sblattero","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and IRCAD University of Eastern Piedmont Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,9,1]]},"reference":[{"key":"2023020106404289100_lam12286-bib-0001","doi-asserted-by":"crossref","first-page":"9716","DOI":"10.1073\/pnas.0305659101","article-title":"The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae","volume":"101","author":"Alsmark","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023020106404289100_lam12286-bib-0002","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1128\/jcm.32.4.942-948.1994","article-title":"Detection of Rochalimaea henselae DNA in specimens from cat scratch disease patients by PCR","volume":"32","author":"Anderson","year":"1994","journal-title":"J Clin Microbiol"},{"key":"2023020106404289100_lam12286-bib-0003","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1128\/jcm.33.9.2358-2365.1995","article-title":"Characterization of a 17-kilodalton antigen of Bartonella henselae reactive with sera from patients with cat scratch disease","volume":"33","author":"Anderson","year":"1995","journal-title":"J Clin Microbiol"},{"key":"2023020106404289100_lam12286-bib-0004","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1128\/jcm.35.8.1931-1937.1997","article-title":"Pitfalls and fallacies of cat scratch disease serology: evaluation of Bartonella henselae-based indirect fluorescence assay and enzyme-linked immunoassay","volume":"35","author":"Bergmans","year":"1997","journal-title":"J Clin Microbiol"},{"key":"2023020106404289100_lam12286-bib-0005","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1749-6632.2003.tb07376.x","article-title":"Clinical impact of persistent Bartonella bacteremia in humans and animals","volume":"990","author":"Chomel","year":"2003","journal-title":"Ann N Y Acad Sci"},{"key":"2023020106404289100_lam12286-bib-0006","doi-asserted-by":"crossref","first-page":"888","DOI":"10.3346\/jkms.2005.20.5.888","article-title":"Detection of Bartonella henselae DNA by polymerase chain reaction in a patient with cat scratch disease: a case report","volume":"20","author":"Chung","year":"2005","journal-title":"J Korean Med Sci"},{"key":"2023020106404289100_lam12286-bib-0007","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev.micro.58.030603.123700","article-title":"Molecular and cellular basis of bartonella pathogenesis","volume":"58","author":"Dehio","year":"2004","journal-title":"Annu Rev Microbiol"},{"key":"2023020106404289100_lam12286-bib-0008","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3109\/00365549609037920","article-title":"Evaluation of serological response to Bartonella henselae, Bartonella quintana and Afipia felis antigens in 64 patients with suspected cat-scratch disease","volume":"28","author":"Dupon","year":"1996","journal-title":"Scand J Infect Dis"},{"key":"2023020106404289100_lam12286-bib-0009","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1002\/pmic.200700670","article-title":"Proteomic analysis of the bacterial pathogen Bartonella henselae and identification of immunogenic proteins for serodiagnosis","volume":"9","author":"Eberhardt","year":"2009","journal-title":"Proteomics"},{"key":"2023020106404289100_lam12286-bib-0010","doi-asserted-by":"crossref","first-page":"e1413","DOI":"10.1542\/peds.2007-1897","article-title":"Beyond cat scratch disease: widening spectrum of Bartonella henselae infection","volume":"121","author":"Florin","year":"2008","journal-title":"Pediatrics"},{"key":"2023020106404289100_lam12286-bib-0011","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1080\/00365540110076705","article-title":"Bartonella henselae infection mimicking a splenic lymphoma","volume":"33","author":"Ghez","year":"2001","journal-title":"Scand J Infect Dis"},{"key":"2023020106404289100_lam12286-bib-0012","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1074\/mcp.M300060-MCP200","article-title":"Comprehensive proteomic profiling of the membrane constituents of a Mycobacterium tuberculosis strain","volume":"2","author":"Gu","year":"2003","journal-title":"Mol Cell Proteomics"},{"issue":"Pt 8","key":"2023020106404289100_lam12286-bib-0013","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1099\/00221287-143-8-2807","article-title":"Heat shock response and groEL sequence of Bartonella henselae and Bartonella quintana","volume":"143","author":"Haake","year":"1997","journal-title":"Microbiology"},{"issue":"Pt 3","key":"2023020106404289100_lam12286-bib-0014","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1099\/0022-1317-73-3-653","article-title":"Construction of solid matrix-antibody-antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen","volume":"73","author":"Hanke","year":"1992","journal-title":"J Gen Virol"},{"key":"2023020106404289100_lam12286-bib-0015","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1128\/CVI.00305-08","article-title":"Development of an immunoglobulin M capture-based enzyme-linked immunosorbent assay for diagnosis of acute infections with Bartonella henselae","volume":"16","author":"Hoey","year":"2009","journal-title":"Clin Vaccine Immunol"},{"key":"2023020106404289100_lam12286-bib-0016","first-page":"8","article-title":"Natural history of Bartonella infections (an exception to Koch's postulate)","volume":"9","author":"Jacomo","year":"2002","journal-title":"Clin Diagn Lab Immunol"},{"key":"2023020106404289100_lam12286-bib-0017","first-page":"152","article-title":"Cat-scratch disease","volume":"83","author":"Klotz","year":"2011","journal-title":"Am Fam Physician"},{"key":"2023020106404289100_lam12286-bib-0018","doi-asserted-by":"crossref","first-page":"373","DOI":"10.4269\/ajtmh.1990.43.373","article-title":"Bb65, a major immunoreactive protein of Bartonella bacilliformis","volume":"43","author":"Knobloch","year":"1990","journal-title":"Am J Trop Med Hyg"},{"key":"2023020106404289100_lam12286-bib-0019","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1128\/jcm.34.9.2270-2274.1996","article-title":"Serological cross-reactions between Bartonella quintana, Bartonella henselae, and Coxiella burnetii","volume":"34","author":"La Scola","year":"1996","journal-title":"J Clin Microbiol"},{"key":"2023020106404289100_lam12286-bib-0020","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1128\/JCM.37.6.1899-1905.1999","article-title":"Culture of Bartonella quintana and Bartonella henselae from human samples: a 5-year experience (1993 to 1998)","volume":"37","author":"La Scola","year":"1999","journal-title":"J Clin Microbiol"},{"issue":"Suppl","key":"2023020106404289100_lam12286-bib-0021","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0896-8411(89)90120-0","article-title":"The mycobacterial GroEL stress protein: a common target of T-cell recognition in infection and autoimmunity","volume":"2","author":"Lamb","year":"1989","journal-title":"J Autoimmun"},{"key":"2023020106404289100_lam12286-bib-0022","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1046\/j.1469-0691.2003.00509.x","article-title":"Cure of bartonella endocarditis of a prosthetic aortic valve without surgery: value of serologic follow-up","volume":"9","author":"Lesprit","year":"2003","journal-title":"Clin Microbiol Infect"},{"key":"2023020106404289100_lam12286-bib-0023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diagmicrobio.2005.10.020","article-title":"Production of recombinant Bartonella henselae 17-kDa protein for antibody-capture enzyme-linked immunosorbent assay","volume":"55","author":"Loa","year":"2006","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"Pt 3","key":"2023020106404289100_lam12286-bib-0024","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1099\/00207713-49-3-1015","article-title":"Evaluation of intraspecies genetic variation within the 60 kDa heat-shock protein gene (groEL) of Bartonella species","volume":"49","author":"Marston","year":"1999","journal-title":"Int J Syst Bacteriol"},{"key":"2023020106404289100_lam12286-bib-0025","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s004310051298","article-title":"Widening of the clinical spectrum of Bartonella henselae infection as recognized through serodiagnostics","volume":"159","author":"Massei","year":"2000","journal-title":"Eur J Pediatr"},{"key":"2023020106404289100_lam12286-bib-0026","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.idc.2005.06.001","article-title":"The expanded spectrum of bartonellosis in children","volume":"19","author":"Massei","year":"2005","journal-title":"Infect Dis Clin North Am"},{"key":"2023020106404289100_lam12286-bib-0027","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/379420a0","article-title":"Protein folding in the central cavity of the GroEL-GroES chaperonin complex","volume":"379","author":"Mayhew","year":"1996","journal-title":"Nature"},{"key":"2023020106404289100_lam12286-bib-0028","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.diagmicrobio.2007.07.017","article-title":"Discovery and analysis of Bartonella henselae antigens for use in clinical serologic assays","volume":"60","author":"McCool","year":"2008","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2023020106404289100_lam12286-bib-0029","doi-asserted-by":"crossref","first-page":"5915","DOI":"10.1128\/IAI.66.12.5915-5920.1998","article-title":"Characterization of human immunoglobulin (Ig) isotype and IgG subclass response to Bartonella henselae infection","volume":"66","author":"McGill","year":"1998","journal-title":"Infect Immun"},{"key":"2023020106404289100_lam12286-bib-0030","doi-asserted-by":"crossref","first-page":"6933","DOI":"10.1128\/IAI.71.12.6933-6942.2003","article-title":"Mitogenic effect of Bartonella bacilliformis on human vascular endothelial cells and involvement of GroEL","volume":"71","author":"Minnick","year":"2003","journal-title":"Infect Immun"},{"key":"2023020106404289100_lam12286-bib-0031","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1128\/iai.64.8.2955-2961.1996","article-title":"Immunity against Yersinia enterocolitica by vaccination with Yersinia HSP60 immunostimulating complexes or Yersinia HSP60 plus interleukin-12","volume":"64","author":"Noll","year":"1996","journal-title":"Infect Immun"},{"key":"2023020106404289100_lam12286-bib-0032","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1089\/10445490050043344","article-title":"The gene encoding the 17-kDa antigen of Bartonella henselae is located within a cluster of genes homologous to the virB virulence operon","volume":"19","author":"Padmalayam","year":"2000","journal-title":"DNA Cell Biol"},{"key":"2023020106404289100_lam12286-bib-0033","doi-asserted-by":"crossref","first-page":"e81112","DOI":"10.1371\/journal.pone.0081112","article-title":"Immunization using GroEL decreases Clostridium difficile intestinal colonization","volume":"8","author":"Pechine","year":"2013","journal-title":"PLoS One"},{"key":"2023020106404289100_lam12286-bib-0034","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1074\/mcp.M600089-MCP200","article-title":"Disease state differentiation and identification of tuberculosis biomarkers via native antigen array profiling","volume":"5","author":"Sartain","year":"2006","journal-title":"Mol Cell Proteomics"},{"key":"2023020106404289100_lam12286-bib-0035","first-page":"145","article-title":"Heat shock proteins as antigens of bacterial and parasitic pathogens","volume":"167","author":"Shinnick","year":"1991","journal-title":"Curr Top Microbiol Immunol"},{"key":"2023020106404289100_lam12286-bib-0036","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0031-6997(24)01380-2","article-title":"Molecular chaperones: biology and prospects for pharmacological intervention","volume":"50","author":"Smith","year":"1998","journal-title":"Pharmacol Rev"},{"key":"2023020106404289100_lam12286-bib-0037","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nri749","article-title":"Roles of heat-shock proteins in innate and adaptive immunity","volume":"2","author":"Srivastava","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"2023020106404289100_lam12286-bib-0038","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1002\/pmic.200401097","article-title":"Bacterial protein microarrays for identification of new potential diagnostic markers for Neisseria meningitidis infections","volume":"5","author":"Steller","year":"2005","journal-title":"Proteomics"},{"key":"2023020106404289100_lam12286-bib-0039","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1128\/CDLI.7.2.251-257.2000","article-title":"Conservation of the 17-kilodalton antigen gene within the genus Bartonella","volume":"7","author":"Sweger","year":"2000","journal-title":"Clin Diagn Lab Immunol"},{"key":"2023020106404289100_lam12286-bib-0040","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.cell.2006.04.027","article-title":"Structural features of the GroEL-GroES Nano-Cage required for rapid folding of encapsulated protein","volume":"125","author":"Tang","year":"2006","journal-title":"Cell"},{"key":"2023020106404289100_lam12286-bib-0041","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.diagmicrobio.2012.06.028","article-title":"Evaluation of IgG ELISA using N-lauroyl-sarcosine-soluble proteins of Bartonella henselae for highly specific serodiagnosis of cat scratch disease","volume":"74","author":"Tsuruoka","year":"2012","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2023020106404289100_lam12286-bib-0042","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/j.1469-0691.2007.01700.x","article-title":"Serological testing for Bartonella henselae infections in The Netherlands: clinical evaluation of immunofluorescence assay and ELISA","volume":"13","author":"Vermeulen","year":"2007","journal-title":"Clin Microbiol Infect"},{"key":"2023020106404289100_lam12286-bib-0043","doi-asserted-by":"crossref","first-page":"e11447","DOI":"10.1371\/journal.pone.0011447","article-title":"Identification of the feline humoral immune response to Bartonella henselae infection by protein microarray","volume":"5","author":"Vigil","year":"2010","journal-title":"PLoS One"},{"key":"2023020106404289100_lam12286-bib-0044","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1128\/iai.59.9.3086-3093.1991","article-title":"Heat shock proteins and antigens of Mycobacterium tuberculosis","volume":"59","author":"Young","year":"1991","journal-title":"Infect Immun"},{"key":"2023020106404289100_lam12286-bib-0045","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1073\/pnas.85.12.4267","article-title":"Stress proteins are immune targets in leprosy and tuberculosis","volume":"85","author":"Young","year":"1988","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023020106404289100_lam12286-bib-0046","doi-asserted-by":"crossref","first-page":"3741","DOI":"10.1128\/JCM.36.12.3741-3742.1998","article-title":"Bartonella henselae-based indirect fluorescence assays are useful for diagnosis of cat scratch disease","volume":"36","author":"Zbinden","year":"1998","journal-title":"J Clin Microbiol"},{"key":"2023020106404289100_lam12286-bib-0047","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.tube.2009.05.005","article-title":"Development and evaluation of a novel multiple-antigen ELISA for serodiagnosis of tuberculosis","volume":"89","author":"Zhang","year":"2009","journal-title":"Tuberculosis (Edinb)"},{"key":"2023020106404289100_lam12286-bib-0048","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1128\/CMR.12.1.19","article-title":"Role of heat shock proteins in protection from and pathogenesis of infectious diseases","volume":"12","author":"Zugel","year":"1999","journal-title":"Clin Microbiol Rev"}],"container-title":["Letters in Applied Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Flam.12286","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Flam.12286","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/lambio\/article-pdf\/59\/3\/253\/49002401\/lambio0253.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/lambio\/article-pdf\/59\/3\/253\/49002401\/lambio0253.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T23:24:06Z","timestamp":1746228246000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/lambio\/article\/59\/3\/253\/6704831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,1]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,9,1]]}},"URL":"https:\/\/doi.org\/10.1111\/lam.12286","relation":{},"ISSN":["1472-765X","0266-8254"],"issn-type":[{"value":"1472-765X","type":"electronic"},{"value":"0266-8254","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,9,1]]},"published":{"date-parts":[[2014,9,1]]}}}