Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60- and 65-kDa heat-shock proteins

Pandey, Janardan P.; Prohászka, Zoltán; Veres, Amarilla; Füst, George; Hurme, Mikko

doi:10.1038/sj.gene.6364033

Cited by 12 publications

(8 citation statements)

References 19 publications

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“…Association of non-GM 3 23 5,13 phenotypes with high responsiveness to MUC1 could aid in identifying subjects who are more likely to benefit from MUC1-based vaccines. For individuals with the low responder phenotype, MUC1 could be fused with appropriate adjuvants, such as heat shock proteins, in order to conceive a vaccine that could potentially generate high antibody responses in the majority of population (Li et al, 2006;Pandey et al, 2004). In accordance with Reis CA et al (1998) and Baldus SE at al (1998), our results regarding the survival of patients at 5 years prove the association between the overexpression of MUC1 and the worse prognosis.…”

supporting

confidence: 73%

Immunohistochemical Profile of Mucins in Gastric Carcinoma

Lazăr¹,

Tăban²

2011

Gastric Carcinoma - Molecular Aspects and Current Advances

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supporting

confidence: 73%

Immunohistochemical Profile of Mucins in Gastric Carcinoma

Lazăr¹,

Tăban²

2011

Gastric Carcinoma - Molecular Aspects and Current Advances

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“…In addition to infections and overexpression/release of Hsps, other factors, such as genetic predisposition, can also regulate the production of these autoantibodies. Our research group reported that a common genetic polymorphism in the promoter region of the interleukin 6 gene and immunoglobulin GM genotypes affect the production of autoantibodies to Hsp60 and Hsp65 (Veres et al 2002c;Pandey et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Circulating anti-heat-shock-protein antibodies in normal pregnancy and preeclampsia

Molvarec

Derzsy

Kocsis

et al. 2009

Cell Stress and Chaperones

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It has been previously reported that circulating anti-heat-shock-protein (Hsp) antibody levels are elevated in cardiovascular disorders. The aim of the present study was to determine circulating antihuman Hsp60, antimycobacterial Hsp65, and antihuman Hsp70 antibody levels in healthy pregnant women and preeclamptic patients and to investigate their relationship to the clinical characteristics of the study subjects, as well as to the markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen), or endothelial injury (fibronectin), oxidative stress (malondialdehyde) and to serum Hsp70 levels. Ninety-three preeclamptic patients and 127 normotensive healthy pregnant women were involved in this case control study. Serum anti-Hsp60, anti-Hsp65, anti-Hsp70, and Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Serum CRP levels were determined by an autoanalyzer using the manufacturer's kit. Plasma von Willebrand factor antigen levels were quantified by ELISA, while plasma fibronectin concentration by nephelometry. Plasma malondialdehyde levels were measured by the thiobarbituric-acid-based colorimetric assay. For statistical analyses, nonparametric methods were applied. Anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibodies were detected in all of our serum samples. There were no significant differences in serum anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibody levels between the control and preeclamptic groups. Serum levels of Hsp70 and CRP, as well as plasma levels of VWF antigen, fibronectin, and malondialdehyde, were significantly higher in preeclamptic patients than in normotensive healthy pregnant women. Serum anti-Hsp60 antibody levels showed significant correlations with serum anti-Hsp65 antibody levels both in the control and the preeclamptic groups (Spearman R = 0.55 and 0.59; p < 0.001, respectively). However, no other relationship was found between clinical features (maternal age, smoking status, parity, body mass index, gestational age at blood draw, systolic and diastolic blood pressure, gestational age at delivery, and fetal birth weight) and measured laboratory parameters of the study subjects and serum anti-Hsp antibody levels in either study group. In conclusion, anti-Hsp60 and anti-Hsp70 antibodies as naturally occurring autoantibodies are present in the peripheral circulation of healthy pregnant women. Nevertheless, humoral immunity against heat shock proteins was not associated with preeclampsia. Further studies are warranted to explore the role of heat shock proteins and immune reactivity to them in the immunobiology of normal pregnancy and preeclampsia.

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“…This difference indicates essential interpopulation differences and underlines the importance of the aim of the present study. A potential explanation for this difference is based on our recent observation on the epistatic interaction between IL-6 and immunoglobulin genes [23] . Interpopulation differences in the reported Km and Gm allotypes and in other, as yet not identified genes might influence our observations and explain the different behavior of heterozygotes in the two study groups.…”

Section: Discussionmentioning

confidence: 99%

Associations between Interleukin-6 Genetic Polymorphisms and Levels of Autoantibodies to 60-kDa Heat-Shock Proteins

Kiszel

Füst²,

Hurme³

et al. 2006

Hum Hered

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Aims: Previously we reported an association between levels of anti-Hsp60 autoantibodies and interleukin-6 (IL-6) –174 SNP in Finnish population. The aim of this study was to investigate the same association in an independent population and to study four recently described SNP in IL-6. Materials and Methods: 313 healthy Hungarian subjects were recruited and genotyped for IL-6 –174(G→C), –9316(T→C), –1363(G→T), +1753(C→G), +2954(G→C). IgG antibodies to Hsp60 were measured by ELISA. LD between SNPs was computed by Haploview 3.2 software. Results: A strong association between IL-6 –174 polymorphism and anti-Hsp60 autoantibody levels was observed. Carriers of –174 CC genotype had significantly lower levels of anti-Hsp60 (p = 0.0052). Eight haplotypes were observed with five SNP-s and autoantibody levels in individuals carrying the most common haplotype (containing allele C of –174) were significantly lower than in all other genotype combinations (p = 0.026). Conclusions: Allele C of –174 promoter polymorphism of the IL-6 gene was repeatedly shown to be associated with low anti-Hsp60 autoantibody levels. Strong linkage in the IL-6 gene was observed and the most frequent haplotype containing the –174 C allele was significantly associated with autoantibody levels. Since the –174 SNP of IL-6 is a functional polymorphism, our results indicate for a direct regulatory effect of IL-6 genotypes in the determination of autoantibody levels.

show abstract

Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60- and 65-kDa heat-shock proteins

Cited by 12 publications

References 19 publications

Immunohistochemical Profile of Mucins in Gastric Carcinoma

Immunohistochemical Profile of Mucins in Gastric Carcinoma

Circulating anti-heat-shock-protein antibodies in normal pregnancy and preeclampsia

Associations between Interleukin-6 Genetic Polymorphisms and Levels of Autoantibodies to 60-kDa Heat-Shock Proteins

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