title: Characterization of humoral immune responses to chlamydial HSP60, CPAF, and CT795 in inflammatory and severe trachoma.
abstract: OBJECTIVE
  Chlamydia trachomatis (Ct) remains the leading global cause of preventable blindness. There are limited data on humoral immune responses in trachoma. Evaluating these responses is important for understanding host-pathogen interactions and informing vaccine design. Antibodies to chlamydial heat shock protein 60 (cHSP60) have been associated with infertility and trachomatous scarring. Other proteins, including chlamydial protease-associated factor (CPAF) and a hypothetical protein unique to the family Chlamydiaceae, CT795, elicit strong immune responses in urogenital infections, but their role in trachomatous disease is unknown.
  
  
  METHODS
  This study was conducted to expand on previous cHSP60 findings and evaluate the association of CPAF and CT795 antibodies with ocular Ct infection and disease. Clinical trachoma grading was performed, and conjunctival samples were obtained from individuals with trachomatous trichiasis (TT; one or more inturned eyelashes) or inflammatory trachoma without trichiasis and control subjects without disease, all of whom resided in trachoma-endemic regions of Nepal. Ct infection was determined using commercial PCR. IgG and IgA tear antibodies against cHSP60, CT795, and CPAF fusion proteins were measured by quantitative ELISA.
  
  
  RESULTS
  Significantly higher IgG antibody levels were found against cHSP60, CPAF, and CT795 in the inflammatory cases compared with levels in the controls (P < 0.005 for all three). Ct infection was independently associated with IgG antibodies against all three immunogens in the inflammatory cases but not in the controls (P = 0.025, P = 0.03 and P = 0.017, respectively). Only IgG antibodies against CPAF were significantly elevated among the TT cases (P = 0.013).
  
  
  CONCLUSIONS
  Among individuals with trachoma, IgG antibody responses to CPAF are likely to be both a marker and risk factor for inflammatory trachoma and severe trachomatous disease.
authors.affiliation: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Skwor
authors.forename: Ram Prasad
authors.initials: RP
authors.lastname: Kandel
authors.forename: Sunniya
authors.initials: S
authors.lastname: Basravi
authors.forename: Aslam
authors.initials: A
authors.lastname: Khan
authors.forename: Bassant
authors.initials: B
authors.lastname: Sharma
authors.forename: Deborah
authors.initials: D
authors.lastname: Dean
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D002648:Child; D002692:Chlamydia trachomatis / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D010450:Endopeptidases / Q000276:immunology*; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins; D013666:Tears / Q000276:immunology; D014141:Trachoma / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D017931:DNA Primers; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D010450:Endopeptidases
references.citation: J Infect Dis. 1994 Mar;169(3):680-3
references.pmid: 8158051
references.citation: J Infect Dis. 1986 May;153(5):870-8
references.pmid: 3009637
references.citation: J Immunol. 2008 Mar 1;180(5):3375-82
references.pmid: 18292563
references.citation: J Infect Dis. 1993 Aug;168(2):415-20
references.pmid: 8335979
references.citation: J Infect Dis. 1993 Dec;168(6):1528-31
references.pmid: 8245540
references.citation: J Infect Dis. 1998 Jan;177(1):256-9
references.pmid: 9419202
references.citation: J Infect Dis. 1997 May;175(5):1153-8
references.pmid: 9129079
references.citation: Infect Immun. 2001 Apr;69(4):2442-7
references.pmid: 11254605
references.citation: Infect Immun. 2007 Feb;75(2):666-76
references.pmid: 17118987
references.citation: Infect Immun. 1997 Jun;65(6):2175-82
references.pmid: 9169748
references.citation: Am J Obstet Gynecol. 1997 Apr;176(4):870-7
references.pmid: 9125613
references.citation: J Exp Med. 2001 Apr 16;193(8):935-42
references.pmid: 11304554
references.citation: Sex Transm Dis. 2008 Feb;35(2):129-35
references.pmid: 18300379
references.citation: J Infect Dis. 1997 Jun;175(6):1453-8
references.pmid: 9180186
references.citation: Curr Opin Infect Dis. 1999 Feb;12(1):67-71
references.pmid: 17035763
references.citation: Infect Immun. 1997 Dec;65(12):4958-64
references.pmid: 9393782
references.citation: J Infect Dis. 1984 Nov;150(5):745-51
references.pmid: 6238106
references.citation: J Immunol Methods. 1998 Sep 1;218(1-2):133-9
references.pmid: 9819130
references.citation: Infect Immun. 1995 Dec;63(12):4704-14
references.pmid: 7591126
references.citation: Microbes Infect. 2005 Mar;7(3):410-20
references.pmid: 15784185
references.citation: PLoS Negl Trop Dis. 2008 Jul 16;2(7):e264
references.pmid: 18628987
references.citation: Br J Ophthalmol. 1989 Apr;73(4):276-82
references.pmid: 2713305
references.citation: J Infect Dis. 1996 Sep;174(3):647-50
references.pmid: 8769630
references.citation: Fertil Steril. 1995 Oct;64(4):730-5
references.pmid: 7672143
references.citation: Infect Immun. 1992 Dec;60(12):5294-7
references.pmid: 1452363
references.citation: JAMA. 2006 Sep 27;296(12):1488-97
references.pmid: 17003397
references.citation: Infect Immun. 2009 Aug;77(8):3218-26
references.pmid: 19487469
references.citation: Eye (Lond). 1998;12 ( Pt 6):1001-6
references.pmid: 10326004
references.citation: Infect Immun. 1996 Aug;64(8):3273-9
references.pmid: 8757864
references.citation: Infect Immun. 1999 Oct;67(10):5518-21
references.pmid: 10496942
references.citation: Hum Reprod. 2006 Jun;21(6):1533-8
references.pmid: 16478761
references.citation: Infect Immun. 2006 Dec;74(12):6722-9
references.pmid: 17015458
references.citation: Infect Immun. 2005 Jul;73(7):4414-9
references.pmid: 15972540
references.citation: Infect Immun. 2006 Mar;74(3):1490-9
references.pmid: 16495519
references.citation: Int J Immunogenet. 2009 Feb;36(1):73-8
references.pmid: 19207939
references.citation: Infect Immun. 1994 Dec;62(12):5491-7
references.pmid: 7960130
references.citation: Infect Immun. 2004 Jul;72(7):3863-8
references.pmid: 15213128
references.citation: Infect Immun. 1993 Mar;61(3):1117-20
references.pmid: 7679373
references.citation: Infect Immun. 2000 Dec;68(12):6979-87
references.pmid: 11083822
references.citation: Nat Rev Immunol. 2005 Feb;5(2):149-61
references.pmid: 15688042
references.citation: J Biol Chem. 2007 Mar 9;282(10):7368-75
references.pmid: 17215251
references.citation: PLoS Med. 2008 Jan 3;5(1):e14
references.pmid: 18177205
references.citation: Infect Immun. 2004 Dec;72(12):7164-71
references.pmid: 15557641
references.citation: Invest Ophthalmol Vis Sci. 2005 Feb;46(2):447-53
references.pmid: 15671268
references.citation: J Biol Chem. 2006 Oct 20;281(42):31495-501
references.pmid: 16940052
references.citation: Infect Immun. 2002 Sep;70(9):5132-9
references.pmid: 12183563
references.citation: Am J Reprod Immunol. 2008 Feb;59(2):99-104
references.pmid: 18211535
references.citation: Infect Immun. 1985 Jun;48(3):847-9
references.pmid: 3997251
references.citation: Arch Ophthalmol. 2004 Apr;122(4):511-6
references.pmid: 15078668
references.citation: Bull World Health Organ. 2004 Nov;82(11):844-51
references.pmid: 15640920
references.citation: Ophthalmology. 1980 Apr;87(4):298-301
references.pmid: 7393535
references.citation: Curr Microbiol. 2004 Jul;49(1):13-21
references.pmid: 15297924
references.citation: Infect Immun. 1991 Mar;59(3):925-31
references.pmid: 1705244
references.citation: Immunology. 2002 Feb;105(2):213-21
references.pmid: 11872097
references.citation: J Cell Biol. 2008 Jul 14;182(1):117-27
references.pmid: 18625845
references.citation: Clin Rheumatol. 2009 Jan;28(1):11-6
references.pmid: 18688674
references.citation: Diagn Microbiol Infect Dis. 2009 Nov;65(3):224-31
references.pmid: 19766431
references.citation: JAMA. 2004 Aug 11;292(6):721-5
references.pmid: 15304470
references.citation: Science. 1999 Feb 26;283(5406):1335-9
references.pmid: 10037605
references.citation: Infect Immun. 1990 Sep;58(9):3061-3
references.pmid: 2387634
references.citation: Biochem Biophys Res Commun. 1995 Mar 17;208(2):697-703
references.pmid: 7695625
references.citation: Sex Transm Infect. 2004 Oct;80(5):415-6
references.pmid: 15459415
references.citation: Infect Immun. 2001 Aug;69(8):4996-5000
references.pmid: 11447178
references.citation: Invest Ophthalmol Vis Sci. 1986 Jan;27(1):64-9
references.pmid: 3484473
references.citation: Bull World Health Organ. 1987;65(4):477-83
references.pmid: 3500800
references.citation: Reg Immunol. 1990-1991;3(4):171-6
references.pmid: 1716948
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1894-9
references.pmid: 16446444