Levels of Antibodies against Human Heat Shock Protein (HSP) 60 in Patients with Glaucoma in Poland

Background

AIM OF THE STUDY:

The aim of the study was to determine if normal-tension glaucoma (NTG) coexists with elevated levels of antibodies against human heat shock protein HSP60.

Material and Methods

STATISTICAL ANALYSIS:

Statistical analyses were performed using STAT software. The normality of distribution of the study variables in groups was assessed with the Shapiro-Wilk test. Because of departures from normality assumptions, the non-parametric Kruskal-Wallis test was used for comparisons. The chi-square test was used to compare frequencies. The entire statistical analysis was performed at the significance level α=0.05. Results were considered statistically significant at p<0.05.

Results

We included a total of 139 patients in the study. Their demographic data are presented in Table 1.

The following levels of antibodies against human HSP60 were measured in the study groups (Figure 1):

The result was not statistically significant (p=0.96).

Discussion

In this study, serum levels of antibodies against human HSP60 were measured in 4 groups of subjects: with NTG, with POAG, with autoimmune rheumatic diseases, and normal controls. In the NTG group, the level of HSP60 antibodies was higher compared to the POAG group and controls, but the difference was not statistically significant. The highest level of antibodies against HSP60 was found in subjects with autoimmune rheumatic diseases, but the difference between this group and the remaining groups was not statistically significant. These findings do not confirm the results of 2 studies performed by Wax et al. [14,16]. In the first study, they demonstrated that patients with glaucoma had elevated levels of antibodies against HSP60, both human and bacterial, based on the comparison between subjects with NTG and POAG, and normal controls. The levels of antibodies against human HSP60 in the NTG subjects and POAG subjects were comparable, but in both groups they were significantly higher compared to controls. The levels of antibodies against bacterial HSP60 were significantly elevated in the NTG subjects compared to the POAG subjects. According to Wax et al., comparable levels of antibodies against human HSP60 in NTG and POAG might suggest a similar mechanism underlying optic disc neuropathy, while elevated levels of antibodies against bacterial HSP60 in the subjects with NTG might indicate a stronger abnormal immune response to bacterial HSP60. In their later study, Wax et al. compared the levels of antibodies against bacterial and human HSP60 in larger groups of patients from the United States and Japan and revealed elevated levels of antibodies against human and bacterial HSP60 in NTG patients compared to POAG patients, who, however, had higher HSP60 antibody levels compared to controls [16]. The results of these 2 studies are not quite consistent, as the earlier study did not find any differences between the levels of antibodies against HSPs in NTG and POAG [14].

The findings by Boehm et al. in Germany do not support the above observations by Wax et al. Boehm et al. measured, among other variables, the levels of antibodies against HSP60 in subjects with POAG and in controls, but did not find elevated HSP60 antibodies in the former compared to the latter [17]. Also, the results of the present study do not confirm the observations by Wax et al. reported from the United States and Japan. We demonstrate lack of significant differences in the levels of antibodies against human HSP60 between NTG and POAG subjects and controls. Subjects’ ages could not have had any impact on this finding, because they were comparable in all studies discussed. The differences may be due to other factors. First of all, antibodies against human HSP60 may also be found in healthy individuals, both neonates and adults [18,19]. Additionally, the international literature now offers increasing evidence for the autoimmune component of atherosclerosis, with an important role of HSPs, including HSP60, in its pathogenesis [13,20,21]. According to recent research, antibodies against HSP60 may play a role in the etiology of cardiomyopathy, including diabetic cardiomyopathy (hence, elevated levels of anti-HSP60 antibodies in diabetes) and atrial fibrillation, but not in arterial hypertension [20]. Another important observation of this study is absence of elevated levels of antibodies against HSP60 in subjects with rheumatic diseases, despite the autoimmune component of their disorder. This finding may be accounted for by the role of antibodies against HSP60 in the pathogenesis of atherosclerosis. Only patients with rheumatic diseases and co-existing atherosclerosis were found to have elevated serum titers of antibodies against HSP60 [22]. Nowadays, rheumatic diseases are increasingly diagnosed in younger patients, and in this study the mean age of the subjects with rheumatic diseases was 47.7 years and none of them had ischemic heart disease. It may be safely assumed that in patients with NTG, HSP60 antibodies would elevate only in patients with coexisting atherosclerosis, which is why these antibodies could not be detected in the sera of the relatively young glaucoma subjects with no history of cardiovascular disease assessed in this study. In the studies from other international centers discussed in this paper, there is no information concerning a possible history of cardiovascular disease in the subjects with NTG and elevated titers of antibodies against HSP60 [14,16].

Conclusions

This study does not confirm the hypothesis that normal-tension glaucoma is associated with elevated blood levels of antibodies against human heat shock protein (HSP) 60. Future studies with larger groups of patients are needed to further investigate the role HSP60 plays in the pathogenesis of glaucoma.