Skip to main content
Top
Published in: European Journal of Clinical Microbiology & Infectious Diseases 1/2017

01-01-2017 | Original Article

Antibody to Chlamydia trachomatis proteins, TroA and HtrA, as a biomarker for Chlamydia trachomatis infection

Authors: K. Hokynar, S. Korhonen, P. Norja, J. Paavonen, M. Puolakkainen

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 1/2017

Login to get access

Abstract

We studied whether antibody to two chlamydial proteins (TroA and HtrA) could be used as biomarkers of Chlamydia trachomatis infection. Methods: Recombinant proteins C. trachomatis TroA and HtrA were used as antigens in enzyme immunoassay (EIA). Both IgG and IgA antibody responses were studied. Results: IgG or IgA antibody to either protein was infrequently detected in sera from healthy blood donors or virgin girls. Patients attending the STI Clinic and patients with perihepatitis had often IgG antibody against TroA (25 and 50 % respectively) and HtrA (21 and 38 % respectively). Especially in sera from patients with chlamydial perihepatitis, the A450nm values with TroA were high (mean 1.591). A positive correlation between C. trachomatis MIF antibody and TroA (r  = 0.7) as well as HtrA (r  = 0.5) antibody was observed in sera from STI clinic patients and perihepatitis patients. Individuals with C. trachomatis infection and positive serology already when seeking medical attention had higher A450nm values for TroA (0.638) and HtrA (0.836) than patients with no marker of previous exposure or with no infection (0.208 and 0.234 respectively). Diagnosis of genital C. trachomatis infection is often NAAT-based, whereas serology has little value in testing for uncomplicated genital C. trachomatis infection. TroA and HtrA antibodies are potential biomarkers for evaluation of ascending and repeated C. trachomatis infection.
Literature
1.
go back to reference Paavonen J (2012) Chlamydia trachomatis infections of the female genital tract: state of the art. Ann Med 44:18–28CrossRefPubMed Paavonen J (2012) Chlamydia trachomatis infections of the female genital tract: state of the art. Ann Med 44:18–28CrossRefPubMed
2.
go back to reference Beatty WL, Byrne GI, Morrison RP (1993) Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci U S A 90:3998–4002CrossRefPubMedPubMedCentral Beatty WL, Byrne GI, Morrison RP (1993) Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci U S A 90:3998–4002CrossRefPubMedPubMedCentral
3.
go back to reference Beatty WL, Morrison RP, Byrne GI (1994) Persistent Chlamydiae: from cell culture to paradigm for chlamydial pathogenesis. Microbiol Rev 58:686–699PubMedPubMedCentral Beatty WL, Morrison RP, Byrne GI (1994) Persistent Chlamydiae: from cell culture to paradigm for chlamydial pathogenesis. Microbiol Rev 58:686–699PubMedPubMedCentral
5.
go back to reference Prusty BK, Siegl C, Hauck P, Hein J, Korhonen SJ, Hiltunen-Back E, Puolakkainen M, Rudel T (2013) Chlamydia trachomatis infection induces replication of latent HHV6. PLoS One 8:e61400CrossRefPubMedPubMedCentral Prusty BK, Siegl C, Hauck P, Hein J, Korhonen SJ, Hiltunen-Back E, Puolakkainen M, Rudel T (2013) Chlamydia trachomatis infection induces replication of latent HHV6. PLoS One 8:e61400CrossRefPubMedPubMedCentral
6.
go back to reference Matsumoto A, Manire GP (1970) Electron microscopic observations on the effects of penicillin on the morphology of Chlamydia psittaci. J Bacteriol 101:278–285PubMedPubMedCentral Matsumoto A, Manire GP (1970) Electron microscopic observations on the effects of penicillin on the morphology of Chlamydia psittaci. J Bacteriol 101:278–285PubMedPubMedCentral
7.
go back to reference Thompson CC, Carabeo RA (2011) An optimal method of iron starvation of the obligate intracellular pathogen, Chlamydia trachomatis. Front Microbiol 2:20CrossRefPubMedPubMedCentral Thompson CC, Carabeo RA (2011) An optimal method of iron starvation of the obligate intracellular pathogen, Chlamydia trachomatis. Front Microbiol 2:20CrossRefPubMedPubMedCentral
8.
go back to reference Raulston JE (1997) Response of Chlamydia trachomatis serovar E to iron restriction in vitro and evidence for iron-regulated chlamydial proteins. Infect Immun 65:4539–4547PubMedPubMedCentral Raulston JE (1997) Response of Chlamydia trachomatis serovar E to iron restriction in vitro and evidence for iron-regulated chlamydial proteins. Infect Immun 65:4539–4547PubMedPubMedCentral
9.
go back to reference Centers for Disease Control and Prevention (2014) Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae 2014. MMWR Recomm Rep 63:1–19 Centers for Disease Control and Prevention (2014) Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae 2014. MMWR Recomm Rep 63:1–19
10.
go back to reference Gérard HC, Krausse-Opatz B, Wang Z, Rudy D, Rao JP, Zeidler H, Schumacher HR, Whittum-Hudson JA, Köhler L, Hudson AP (2001) Expression of Chlamydia trachomatis genes encoding products required for DNA synthesis and cell division during active versus persistent infection. Mol Microbiol 41:731–741CrossRefPubMed Gérard HC, Krausse-Opatz B, Wang Z, Rudy D, Rao JP, Zeidler H, Schumacher HR, Whittum-Hudson JA, Köhler L, Hudson AP (2001) Expression of Chlamydia trachomatis genes encoding products required for DNA synthesis and cell division during active versus persistent infection. Mol Microbiol 41:731–741CrossRefPubMed
11.
go back to reference Nicholson T, Stephens RS (2002) Chlamydial genomic transcriptional profile for penicillin-induced persistence. In: Schachter J, Christiansen G, Clarke IN, et al, eds. Chlamydial infections. Proceedings of the Tenth International Symposium on Human Chlamydial Infections. San Francisco, CA: International Chlamydia Symposium, pp. 611–614 Nicholson T, Stephens RS (2002) Chlamydial genomic transcriptional profile for penicillin-induced persistence. In: Schachter J, Christiansen G, Clarke IN, et al, eds. Chlamydial infections. Proceedings of the Tenth International Symposium on Human Chlamydial Infections. San Francisco, CA: International Chlamydia Symposium, pp. 611–614
12.
go back to reference Belland RJ, Nelson DE, Virok D, Crane DD, Hogan D, Sturdevant D, Beatty WL, Caldwell HD (2003) Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation. Proc Natl Acad Sci U S A 100:15971–15976CrossRefPubMedPubMedCentral Belland RJ, Nelson DE, Virok D, Crane DD, Hogan D, Sturdevant D, Beatty WL, Caldwell HD (2003) Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation. Proc Natl Acad Sci U S A 100:15971–15976CrossRefPubMedPubMedCentral
13.
go back to reference Gérard HC, Whittum-Hudson JA, Schumacher HR, Hudson AP (2004) Differential expression of three Chlamydia trachomatis hsp60-encoding genes in active vs. persistent infections. Microb Pathog 36:35–39CrossRefPubMed Gérard HC, Whittum-Hudson JA, Schumacher HR, Hudson AP (2004) Differential expression of three Chlamydia trachomatis hsp60-encoding genes in active vs. persistent infections. Microb Pathog 36:35–39CrossRefPubMed
14.
go back to reference Rodgers AK, Budrys NM, Gong S, Wang J, Holden A, Schenken RS, Zhong G (2011) Genome-wide identification of Chlamydia trachomatis antigens associated with tubal factor infertility. Fertil Steril 96:715–721CrossRefPubMedPubMedCentral Rodgers AK, Budrys NM, Gong S, Wang J, Holden A, Schenken RS, Zhong G (2011) Genome-wide identification of Chlamydia trachomatis antigens associated with tubal factor infertility. Fertil Steril 96:715–721CrossRefPubMedPubMedCentral
15.
go back to reference Budrys NM, Gong S, Rodgers AK, Wang J, Louden C, Shain R, Schenken RS, Zhong G (2012) Chlamydia trachomatis antigens recognized in women with tubal factor infertility, normal fertility, and acute infection. Obstet Gynecol 119:1009–1016CrossRefPubMedPubMedCentral Budrys NM, Gong S, Rodgers AK, Wang J, Louden C, Shain R, Schenken RS, Zhong G (2012) Chlamydia trachomatis antigens recognized in women with tubal factor infertility, normal fertility, and acute infection. Obstet Gynecol 119:1009–1016CrossRefPubMedPubMedCentral
16.
go back to reference Bannantine JP, Rockey DD (1999) Use of primate model system to identify Chlamydia trachomatis protein antigens recognized uniquely in the context of infection. Microbiology 145:2077–2085CrossRefPubMed Bannantine JP, Rockey DD (1999) Use of primate model system to identify Chlamydia trachomatis protein antigens recognized uniquely in the context of infection. Microbiology 145:2077–2085CrossRefPubMed
17.
go back to reference Miller JD, Sal MS, Schell M, Whittimore JD, Raulston JE (2009) Chlamydia trachomatis YtgA is an iron-binding periplasmic protein induced by iron restriction. Microbiology 155:2884–2894CrossRefPubMedPubMedCentral Miller JD, Sal MS, Schell M, Whittimore JD, Raulston JE (2009) Chlamydia trachomatis YtgA is an iron-binding periplasmic protein induced by iron restriction. Microbiology 155:2884–2894CrossRefPubMedPubMedCentral
18.
go back to reference Patel P, De Boer L, Timms P, Huston WM (2014) Evidence of a conserved role for Chlamydia HtrA in the replication phase of the chlamydial developmental cycle. Microbes Infect 16:690–694CrossRefPubMed Patel P, De Boer L, Timms P, Huston WM (2014) Evidence of a conserved role for Chlamydia HtrA in the replication phase of the chlamydial developmental cycle. Microbes Infect 16:690–694CrossRefPubMed
19.
go back to reference Huston WM, Swedberg JE, Harris JM, Walsh TP, Mathews SA, Timms P (2007) The temperature activated HtrA protease from pathogen Chlamydia trachomatis acts as both a chaperone and protease at 37 degrees C. FEBS Lett 581:3382–3386CrossRefPubMed Huston WM, Swedberg JE, Harris JM, Walsh TP, Mathews SA, Timms P (2007) The temperature activated HtrA protease from pathogen Chlamydia trachomatis acts as both a chaperone and protease at 37 degrees C. FEBS Lett 581:3382–3386CrossRefPubMed
20.
go back to reference Paukku M, Närvänen A, Puolakkainen M, Dreesbach K, Tiitinen A, Hao W, Anttila TI, Paavonen J (1998) Detection of Chlamydia trachomatis antibodies by two novel tests - rELISA and peptide EIA. Int J STD AIDS 9:604–607CrossRefPubMed Paukku M, Närvänen A, Puolakkainen M, Dreesbach K, Tiitinen A, Hao W, Anttila TI, Paavonen J (1998) Detection of Chlamydia trachomatis antibodies by two novel tests - rELISA and peptide EIA. Int J STD AIDS 9:604–607CrossRefPubMed
21.
go back to reference Närvänen A, Puolakkainen M, Hao W, Kino K, Suni J (1997) Detection of antibodies to Chlamydia trachomatis with peptide-based species-specific enzyme immunoassay. Inf Dis Obstet Gynecol 5:349–354 Närvänen A, Puolakkainen M, Hao W, Kino K, Suni J (1997) Detection of antibodies to Chlamydia trachomatis with peptide-based species-specific enzyme immunoassay. Inf Dis Obstet Gynecol 5:349–354
22.
go back to reference Puolakkainen M, Saikku P, Leinonen M, Nurminen M, Väänänen P, Mäkelä PH (1985) Comparative sensitivity of different serological tests for detecting chlamydial antibodies in perihepatitis. J Clin Pathol 38:929–932CrossRefPubMedPubMedCentral Puolakkainen M, Saikku P, Leinonen M, Nurminen M, Väänänen P, Mäkelä PH (1985) Comparative sensitivity of different serological tests for detecting chlamydial antibodies in perihepatitis. J Clin Pathol 38:929–932CrossRefPubMedPubMedCentral
23.
go back to reference Gencay M, Koskiniemi M, Ämmälä P, Fellman V, Närvänen A, Wahlström T, Vaheri A, Puolakkainen M (2000) Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery. APMIS 108:584–588CrossRefPubMed Gencay M, Koskiniemi M, Ämmälä P, Fellman V, Närvänen A, Wahlström T, Vaheri A, Puolakkainen M (2000) Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery. APMIS 108:584–588CrossRefPubMed
24.
go back to reference Huston WM, Theodoropoulos C, Mathews SA, Timms P (2008) Chlamydia trachomatis responds to heat shock, penicillin induced persistence, and IFN-gamma persistence by altering levels of the extracytoplasmic stress response protease HtrA. BMC Microbiol 8:190CrossRefPubMedPubMedCentral Huston WM, Theodoropoulos C, Mathews SA, Timms P (2008) Chlamydia trachomatis responds to heat shock, penicillin induced persistence, and IFN-gamma persistence by altering levels of the extracytoplasmic stress response protease HtrA. BMC Microbiol 8:190CrossRefPubMedPubMedCentral
25.
go back to reference Wu X, Lei L, Gong S, Chen D, Flores R, Zhong G (2011) The chlamydial periplasmic stress response serine protease cHtrA is secreted into host cell cytosol. BMC Microbiol 11:87CrossRefPubMedPubMedCentral Wu X, Lei L, Gong S, Chen D, Flores R, Zhong G (2011) The chlamydial periplasmic stress response serine protease cHtrA is secreted into host cell cytosol. BMC Microbiol 11:87CrossRefPubMedPubMedCentral
26.
go back to reference Raulston JE, Miller JD, Davis CH, Schell M, Baldwin A, Ferguson K, Lane H (2007) Identification of an iron-responsive protein that is antigenic in patients with Chlamydia trachomatis genital infections. FEMS Immunol Med Microbiol 51:569–576CrossRefPubMed Raulston JE, Miller JD, Davis CH, Schell M, Baldwin A, Ferguson K, Lane H (2007) Identification of an iron-responsive protein that is antigenic in patients with Chlamydia trachomatis genital infections. FEMS Immunol Med Microbiol 51:569–576CrossRefPubMed
27.
go back to reference Laurila A, Bloigu A, Näyhä S, Hassi J, Leinonen M, Saikku P (1997) Chronic Chlamydia pneumoniae infection is associated with a serum lipid profile known to be a risk factor for atherosclerosis. Arterioscler Thromb Vasc Biol 17:2910–2913CrossRefPubMed Laurila A, Bloigu A, Näyhä S, Hassi J, Leinonen M, Saikku P (1997) Chronic Chlamydia pneumoniae infection is associated with a serum lipid profile known to be a risk factor for atherosclerosis. Arterioscler Thromb Vasc Biol 17:2910–2913CrossRefPubMed
28.
go back to reference Huston WM, Armitage CW, Lawrence A, Gloeckl S, Bell SJ, Debattista J, Allan JA, Timms P, Queensland Clinical Chlamydia Research Network (2010) HtrA, RseP, and Tsp proteins do not elicit a pathology-related serum IgG response during sexually transmitted infection with Chlamydia trachomatis. J Reprod Immunol 85:168–171CrossRefPubMed Huston WM, Armitage CW, Lawrence A, Gloeckl S, Bell SJ, Debattista J, Allan JA, Timms P, Queensland Clinical Chlamydia Research Network (2010) HtrA, RseP, and Tsp proteins do not elicit a pathology-related serum IgG response during sexually transmitted infection with Chlamydia trachomatis. J Reprod Immunol 85:168–171CrossRefPubMed
29.
go back to reference Finco O, Frigimelica E, Buricchi F, Petracca R, Galli G, Faenzi E, Meoni E, Bonci A, Agnusdei M, Nardelli F, Bartolini E, Scarselli M, Caproni E, Laera D, Zedda L, Skibinski D, Giovinazzi S, Bastone R, Ianni E, Cevenini R, Grandi G, Grifantini R (2011) Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines. Proc Natl Acad Sci U S A 108:9969–9974CrossRefPubMedPubMedCentral Finco O, Frigimelica E, Buricchi F, Petracca R, Galli G, Faenzi E, Meoni E, Bonci A, Agnusdei M, Nardelli F, Bartolini E, Scarselli M, Caproni E, Laera D, Zedda L, Skibinski D, Giovinazzi S, Bastone R, Ianni E, Cevenini R, Grandi G, Grifantini R (2011) Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines. Proc Natl Acad Sci U S A 108:9969–9974CrossRefPubMedPubMedCentral
30.
go back to reference Phillips Campbell R, Kintner J, Whittimore J, Schoborg RV (2012) Chlamydia muridarum enters a viable but non-infectious state in amoxicillin-treated BALB/c mice. Microbes Infect 14:1177–1185CrossRefPubMedPubMedCentral Phillips Campbell R, Kintner J, Whittimore J, Schoborg RV (2012) Chlamydia muridarum enters a viable but non-infectious state in amoxicillin-treated BALB/c mice. Microbes Infect 14:1177–1185CrossRefPubMedPubMedCentral
31.
go back to reference Hudson AP, McEntee CM, Reacher M, Whittum-Hudson JA, Taylor HR (1992) Inapparent ocular infection by Chlamydia trachomatis in experimental and human trachoma. Curr Eye Res 11:279–283CrossRefPubMed Hudson AP, McEntee CM, Reacher M, Whittum-Hudson JA, Taylor HR (1992) Inapparent ocular infection by Chlamydia trachomatis in experimental and human trachoma. Curr Eye Res 11:279–283CrossRefPubMed
32.
go back to reference Dean D, Suchland RJ, Stamm WE (2000) Evidence for long-term cervical persistence of Chlamydia trachomatis by omp1 genotyping. J Infect Dis 182:909–916CrossRefPubMed Dean D, Suchland RJ, Stamm WE (2000) Evidence for long-term cervical persistence of Chlamydia trachomatis by omp1 genotyping. J Infect Dis 182:909–916CrossRefPubMed
33.
go back to reference Puolakkainen M, Vesterinen E, Purola E, Saikku P, Paavonen J (1986) Persistence of chlamydial antibodies after pelvic inflammatory disease. J Clin Microbiol 23:924–928PubMedPubMedCentral Puolakkainen M, Vesterinen E, Purola E, Saikku P, Paavonen J (1986) Persistence of chlamydial antibodies after pelvic inflammatory disease. J Clin Microbiol 23:924–928PubMedPubMedCentral
34.
go back to reference Horner PJ, Wills GS, Reynolds R, Johnson AM, Muir DA, Winston A, Broadbent AJ, Parker D, McClure MO (2013) Effect of time since exposure to Chlamydia trachomatis on chlamydia antibody detection in women: a cross-sectional study. Sex Transm Infect 89:398–403CrossRefPubMed Horner PJ, Wills GS, Reynolds R, Johnson AM, Muir DA, Winston A, Broadbent AJ, Parker D, McClure MO (2013) Effect of time since exposure to Chlamydia trachomatis on chlamydia antibody detection in women: a cross-sectional study. Sex Transm Infect 89:398–403CrossRefPubMed
35.
go back to reference Stansfield SH, Patel P, Debattista J, Armitage CW, Cunningham K, Timms P, Allan J, Mittal A, Huston WM (2013) Proof of concept: a bioinformatic and serological screening method for identifying new peptide antigens for Chlamydia trachomatis related sequelae in women. Results Immunol 3:33–39CrossRefPubMedPubMedCentral Stansfield SH, Patel P, Debattista J, Armitage CW, Cunningham K, Timms P, Allan J, Mittal A, Huston WM (2013) Proof of concept: a bioinformatic and serological screening method for identifying new peptide antigens for Chlamydia trachomatis related sequelae in women. Results Immunol 3:33–39CrossRefPubMedPubMedCentral
Metadata
Title
Antibody to Chlamydia trachomatis proteins, TroA and HtrA, as a biomarker for Chlamydia trachomatis infection
Authors
K. Hokynar
S. Korhonen
P. Norja
J. Paavonen
M. Puolakkainen
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 1/2017
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-016-2769-7

Other articles of this Issue 1/2017

European Journal of Clinical Microbiology & Infectious Diseases 1/2017 Go to the issue