Antibody Response to the 60‐kDa Chlamydial Heat‐Shock Protein Is Associated with Scarring Trachoma

Peeling, Rosanna W.; Bailey, Robin L.; Conway, David J.; Holland, Martin J.; Campbell, Alison E.; Jallow, Ousman; Whittle, Hilton; Mabey, David

doi:10.1086/517367

Cited by 81 publications

(53 citation statements)

References 14 publications

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“…Some have proposed that IFNg-induced chlamydial persistence may lead to chronic inflammation and tissue damage 36,37 partly through the induction of putative sensitizing antigens such as chlamydial heat shock protein 60 (Chsp60). 38 Antibodies to Chsp60 have been found to be associated with scarring sequelae of chlamydial infection in the eye and the genital tract, 39,40 and it has been shown that IFNg is capable of mediating overexpression of Hsp 60 in vitro in HeLa cells. 37 The role of this IFNg-mediated induction of Hsp 60 in vivo has not been established.…”

Section: Discussionmentioning

confidence: 99%

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

et al. 2005

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Experimental evidence implicates interferon gamma (IFNg) in protection from and resolution of chlamydial infection. Conversely, interleukin 10 (IL10) is associated with susceptibility and persistence of infection and pathology. We studied genetic variation within the IL10 and IFNg loci in relation to the risk of developing severe complications of human ocular Chlamydia trachomatis infection. A total of 651 Gambian subjects with scarring trachoma, of whom 307 also had potentially blinding trichiasis and pair-matched controls with normal eyelids, were screened for associations between single-nucleotide polymorphisms (SNPs), SNP haplotypes and the risk of disease. MassEXTEND (Sequenom) and MALDI-TOF mass spectrometry were used for detection and analysis of SNPs and the programs PHASE and SNPHAP used to infer haplotypes from population genetic data. Multivariate conditional logistic regression analysis identified IL10 and IFNg SNP haplotypes associated with increased risk of both trachomatous scarring and trichiasis. SNPs in putative IFNg and IL10 regulatory regions lay within the disease-associated haplotypes. The IFNg þ 874A allele, previously linked to lower IFNg production, lies in the IFNg risk haplotype and was more common among cases than controls, but not significantly so. The promoter IL10-1082G allele, previously associated with high IL10 expression, is in both susceptibility and resistance haplotypes.

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Section: Discussionmentioning

confidence: 99%

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

et al. 2005

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“…4 -6 Chlamydial Hsp60 seroreactivity has also been previously implicated in the pathogenesis of chlamydial infections and in the development of severe sequelae after infections. 11,12,[21][22][23][24][25] It has also been directly linked to the pathogenesis of atherosclerosis, 14,26 and quite recently a strong correlation between anti-Hsp60 IgG levels and coronary heart disease was reported. 27 It has therefore been suggested that Hsps may be the link between C pneumoniae infections and atherogenesis.…”

Section: Discussionmentioning

confidence: 99%

Serum Immunoglobulin G Antibodies to Chlamydial Heat Shock Protein 60 but Not to Human and Bacterial Homologs Are Associated With Coronary Artery Disease

et al. 2002

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Background— Evidence for an association between Chlamydia pneumoniae infection and coronary artery disease (CAD) has been reported by numerous studies, cross-reactive heat shock protein (Hsp) antibody responses have been causally linked to CAD, and the severity of chlamydial disease pathogenesis correlates with Hsp serology. Our aim was to determine if chlamydial Hsp (cHsp) antibody responses are predictive of CAD. Methods and Results— Patients were recruited in a case-control study: 250 cases had angiographically significant CAD (stenosis ≥70%), and 250 controls had normal coronary arteries (stenosis <10%). Serum immunoglobulin G reactivity to Hsp10 and Hsp60 antigens (chlamydial, Escherichia coli , and human), and C pneumoniae whole organisms were measured by ELISA. Univariate analysis confirmed that classical CAD risk factors were predictors of CAD. Univariate analysis showed that cHsp60 ( P = 0.001, OR 3.9), cHsp10 ( P =0.045, OR 3.8), E coli Hsp60 ( P =0.04, OR 1.5) and C pneumoniae ( P =0.03, OR 1.8) ELISA optical density (OD) values were significantly different between cases and controls. Multivariate analysis found that only upper-quintile cHsp60 seroreactivity remained a significant predictor of CAD after controlling for classical CAD risk factors and seroreactivity to the other antigens (cHsp60 OD, P =0.005, OR 3.9 per OD unit; cHsp60 quintile, 5 versus 1 to 4; P =0.01, OR 2.1). Conclusions— The presence of elevated anti-cHsp60 immunoglobulin G antibodies, but not anti-human or anti– E coli homologs, was independently associated with CAD. This finding argues against previous suggestions that cross-reactive or autoimmune Hsp60 responses may contribute to disease progression. High anti-cHsp60 antibody response appears to identify the subset of patients with chlamydial infection and significant CAD.

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“…The levels of chlamydial HSP60 antibodies are predictive for an increased risk of pelvic inflammatory disease in women [18]. They also correlate with other pathologic sequelae of C. trachomatis infections, such as tubal factor infertility, habitual abortion, endometriosis, ectopic pregnancy [19±24], and scarring trachoma [25]. Only a few reports have thus far been published of the antibody response to C. pneumoniae HSP60 [26±29].…”

Section: Hsp60 Antibodies and Pathogenesis Of Chlamydial Diseasesmentioning

confidence: 99%

Heat Shock Protein 60 Specific T‐Cell Response in Chlamydial Infections

Kinnunen

Surcel²

2001

Scand J Immunol

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Heat shock proteins (HSPs) of most pathogens, including Chlamydia, are major immune targets of both humoral-and cell-mediated immune mechanisms. During the last decade, many investigators have focused their research to elucidate the complex relationship of chlamydial HSPs, especially chlamydial HSP60, and the host immune response. A central issue is whether the pathologic mechanisms in chronic chlamydial diseases are associated with an enhanced immune response to chlamydial HSP60 which can mediate tissue destruction through cytotoxic reactions, or whether they are related to the Th2 type of response that eventually leads to partial or temporary suppression of an effective antichlamydial response. Our review highlights the available knowledge between immune responses to chlamydial HSP60 and chronic chlamydial infections in human.

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Antibody Response to the 60‐kDa Chlamydial Heat‐Shock Protein Is Associated with Scarring Trachoma

Cited by 81 publications

References 14 publications

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

Serum Immunoglobulin G Antibodies to Chlamydial Heat Shock Protein 60 but Not to Human and Bacterial Homologs Are Associated With Coronary Artery Disease

Heat Shock Protein 60 Specific T‐Cell Response in Chlamydial Infections

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