Characterization of humoral immune responses to chlamydial HSP60, CPAF, and CT795 in inflammatory and severe trachoma.
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.
Skwor
Troy
T
Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
Kandel
Ram Prasad
RP
Basravi
Sunniya
S
Khan
Aslam
A
Sharma
Bassant
B
Dean
Deborah
D
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*
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
J Infect Dis. 1994 Mar;169(3):680-3
8158051
J Infect Dis. 1986 May;153(5):870-8
3009637
J Immunol. 2008 Mar 1;180(5):3375-82
18292563
J Infect Dis. 1993 Aug;168(2):415-20
8335979
J Infect Dis. 1993 Dec;168(6):1528-31
8245540
J Infect Dis. 1998 Jan;177(1):256-9
9419202
J Infect Dis. 1997 May;175(5):1153-8
9129079
Infect Immun. 2001 Apr;69(4):2442-7
11254605
Infect Immun. 2007 Feb;75(2):666-76
17118987
Infect Immun. 1997 Jun;65(6):2175-82
9169748
Am J Obstet Gynecol. 1997 Apr;176(4):870-7
9125613
J Exp Med. 2001 Apr 16;193(8):935-42
11304554
Sex Transm Dis. 2008 Feb;35(2):129-35
18300379
J Infect Dis. 1997 Jun;175(6):1453-8
9180186
Curr Opin Infect Dis. 1999 Feb;12(1):67-71
17035763
Infect Immun. 1997 Dec;65(12):4958-64
9393782
J Infect Dis. 1984 Nov;150(5):745-51
6238106
J Immunol Methods. 1998 Sep 1;218(1-2):133-9
9819130
Infect Immun. 1995 Dec;63(12):4704-14
7591126
Microbes Infect. 2005 Mar;7(3):410-20
15784185
PLoS Negl Trop Dis. 2008 Jul 16;2(7):e264
18628987
Br J Ophthalmol. 1989 Apr;73(4):276-82
2713305
J Infect Dis. 1996 Sep;174(3):647-50
8769630
Fertil Steril. 1995 Oct;64(4):730-5
7672143
Infect Immun. 1992 Dec;60(12):5294-7
1452363
JAMA. 2006 Sep 27;296(12):1488-97
17003397
Infect Immun. 2009 Aug;77(8):3218-26
19487469
Eye (Lond). 1998;12 ( Pt 6):1001-6
10326004
Infect Immun. 1996 Aug;64(8):3273-9
8757864
Infect Immun. 1999 Oct;67(10):5518-21
10496942
Hum Reprod. 2006 Jun;21(6):1533-8
16478761
Infect Immun. 2006 Dec;74(12):6722-9
17015458
Infect Immun. 2005 Jul;73(7):4414-9
15972540
Infect Immun. 2006 Mar;74(3):1490-9
16495519
Int J Immunogenet. 2009 Feb;36(1):73-8
19207939
Infect Immun. 1994 Dec;62(12):5491-7
7960130
Infect Immun. 2004 Jul;72(7):3863-8
15213128
Infect Immun. 1993 Mar;61(3):1117-20
7679373
Infect Immun. 2000 Dec;68(12):6979-87
11083822
Nat Rev Immunol. 2005 Feb;5(2):149-61
15688042
J Biol Chem. 2007 Mar 9;282(10):7368-75
17215251
PLoS Med. 2008 Jan 3;5(1):e14
18177205
Infect Immun. 2004 Dec;72(12):7164-71
15557641
Invest Ophthalmol Vis Sci. 2005 Feb;46(2):447-53
15671268
J Biol Chem. 2006 Oct 20;281(42):31495-501
16940052
Infect Immun. 2002 Sep;70(9):5132-9
12183563
Am J Reprod Immunol. 2008 Feb;59(2):99-104
18211535
Infect Immun. 1985 Jun;48(3):847-9
3997251
Arch Ophthalmol. 2004 Apr;122(4):511-6
15078668
Bull World Health Organ. 2004 Nov;82(11):844-51
15640920
Ophthalmology. 1980 Apr;87(4):298-301
7393535
Curr Microbiol. 2004 Jul;49(1):13-21
15297924
Infect Immun. 1991 Mar;59(3):925-31
1705244
Immunology. 2002 Feb;105(2):213-21
11872097
J Cell Biol. 2008 Jul 14;182(1):117-27
18625845
Clin Rheumatol. 2009 Jan;28(1):11-6
18688674
Diagn Microbiol Infect Dis. 2009 Nov;65(3):224-31
19766431
JAMA. 2004 Aug 11;292(6):721-5
15304470
Science. 1999 Feb 26;283(5406):1335-9
10037605
Infect Immun. 1990 Sep;58(9):3061-3
2387634
Biochem Biophys Res Commun. 1995 Mar 17;208(2):697-703
7695625
Sex Transm Infect. 2004 Oct;80(5):415-6
15459415
Infect Immun. 2001 Aug;69(8):4996-5000
11447178
Invest Ophthalmol Vis Sci. 1986 Jan;27(1):64-9
3484473
Bull World Health Organ. 1987;65(4):477-83
3500800
Reg Immunol. 1990-1991;3(4):171-6
1716948
Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1894-9
16446444