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Chlamydia pneumoniae may trigger atherogenesis. Chlamydia trachomatis (CT) can also induce endothelial activation. However, its role in metabolic syndrome (METS), a proatherogenic entity, has remained unexplored. In this study the frequencies of IgA and IgG anti-CT antibodies were evaluated by immunoenzymatic assay in METS patients and healthy controls. The survey included 238 individuals (148 with METS). The mean age was 59.7 years. IgA anti-CT antibodies were found significantly more frequently in METS patients (16.9%) than in controls (5.6%) (P= 0.015). The role of such IgA response in METS should be further investigated.
Metabolic syndrome is a proinflammatory and prothrombotic state which leads to cardiovascular disease. METS is notable for generating a chronic inflammatory response (1, 2). Chlamydia are obligatory intracellular pathogens with a biphasic life cycle. In extracellular sites, their elementary bodies activate macrophages and lymphocytes, with consequent release of tumor necrosis factor and gamma-interferon (3).
Infection with Chlamydia pneumoniae can be considered a contributor to atherogenesis, but it is not an independent risk factor for atherosclerotic disease (4, 5). CT, our focus in this study, is predominantly sexually transmitted, and causes eye and urogenital infections (6). Of interest, C. pneumoniae and the CT subtypes H and L infect human endothelial cells and induce a procoagulant state (7).
Exposure to CT in patients with atherosclerotic disease has rarely been evaluated (8). The relationship of CT with METS has not so far been addressed. We herein evaluate the frequency of IgA and IgG anti-CT in patients with METS and in controls.
This cross-sectional study includes individuals with METS who were followed at our Cardiometabolic Risk Outpatient Clinic. Three groups of individuals were evaluated: patients with METS without cardiac events (non-complicated METS); patients with METS and previous cardiac events (acute myocardial infarction, acute coronary syndrome, myocardial revascularization surgery); and healthy controls. METS was diagnosed according to the classical criteria of the NCEP (9). Healthy controls paired by sex and age were selected from blood donors. Informed consent was obtained from all individuals who entered the study. The study was approved by the local ethics committee.
IgA and IgG specific antibodies to the outer CT membrane protein were evaluated by immunoenzymatic assay, IgA antibodies with sensitivity 95% and specificity 98% and IgG antibodies with sensitivity 96% and specificity 100%. The lipopolysaccharide responsible for most of the cross-reactions with other species of Chlamydia was not included in the microplate. For both isotypes, titers of greater than 1.1 units were considered positive (10, 11).
The χ2 test was used to compare the discontinuous variables, and Student's t test to compare the continuous variables. To estimate the degree of association of anti-CT antibodies with METS, the ORs with a 95%CI were calculated. Logistic regression was used to adjust the confounding factors (sex and age). Data were analyzed by the SPSS for Windows program, version 11.5, (Chicago, IL, USA).
Overall, 238 individuals were included in the study (77.2% women, 22.8% men). The METS group without previous cardiac events (non-complicated METS) was comprised of 101 patients; there were 47 patients with METS and previous cardiac events, and 90 individuals in the group of healthy controls. Female patients predominated in both groups with METS, the difference in proportion of men and women not being significant in comparison to the healthy control group. The mean age (59.7 years) did not significantly differ between patients with METS and controls. IgA anti-CT antibodies were found more frequently in METS patients (16.9%) than in controls (5.6%) (P= 0.015). After adjustment for sex and age, high concentrations of IgA anti-CT were significantly associated with occurrence of METS (OR = 3.4; CI95% 1.2–9,4; P= 0.015) (Table 1). IgA anti-CT antibodies were found more frequently in non-complicated METS than in controls (P= 0.013). No significant differences were identified when the other groups were compared (Table 2). After adjustment for age and sex, the association of IgA anti-CT with non-complicated METS remained definite (OR = 3.6; CI95% 1.32–10,2; P= 0.015).
Table 1. Association between anti-CT IgA and anti-CT IgG and METS
|Class of anti-CT antibodies||Number of patients/%||OR†||CI95%|
|IgA||25 (16.9)||5 (5.6)||3.4||1.2–9.4*|
|IgG||6 (4.1)||2 (2.2)||1.8|| 0.4–9.5**|
Table 2. Prevalence of anti-CT IgA and anti-CT IgG antibodies in individuals with METS‡ (with and without cardiac events) and controls
|Class of anti-CT antibodies||Number of patients/%|
|IgA|| 18 (17.8)*,**|| 7 (14.9)||5 (5.6)|
|IgG||3 (3.0)***||3 (6.4)||2 (2.2)|
METS has variously been reported to be more frequent in men (12), occur equally in both sexes (13) or, as in our study, predominate in women (14). The mean age of our patients with METS is in agreement with data from a previous study (14).
The increased IgA anti-CT responses in our patients with METS (mostly non-complicated) has not previously been described in published reports. The meaning of this finding is, as yet, unknown. Our reason for testing the IgA isotype was based on the known CT tropism for mucous membranes (15). This IgA response might reflect recent exposure to the pathogen, but this is a hypothetical possibility.
Our subgroup of patients with METS and previous cardiac events can safely be assumed to be comprised of individuals with established atherosclerosis. In this specific subpopulation, the prevalence of anti-CT antibodies was not increased in comparison to controls. We do not know why the IgA anti-CT response predominated in patients with non-complicated METS in our study.
There is a notable scarcity of published reports concerning CT and atherosclerotic disease. Murine exposure to CT can trigger respiratory infection and later, cardiovascular disease (16). The phosphatidylcholine metabolism derived from low density lipoprotein is accelerated in the presence of CT infection (17). Nasal exposure of apolipoprotein E-deficient mice to C. pneumoniae and CT accelerated aortic atheromatosis (18). Cardiomyopathy has been documented in one patient infected by CT and with a previous history of prostatitis (19).
Our study has limitations. Although high concentrations of IgA anti-CT occurred more frequently in METS than in healthy controls, we emphasize that the overall frequency of positive test in METS was relatively small (16.9%). Moreover, test positivity in controls was not negligible (5.6%). Although the controls did not fulfill the classical criteria for METS, the eventual occurrence of isolated features of METS in these individuals could also reduce the significance of our findings.
In summary, IgA anti-CT antibodies were found significantly more frequently in METS patients than controls. This IgA anti-CT response, presumably of the acute phase, predominated in patients with non-complicated METS. The possible link between CT exposure and METS warrants further studies.