Close association of Chlamydia pneumoniae IgA seropositivity by ELISA with the presence of coronary artery stenosis in haemodialysis patients
Masato Nishimura1,
Tetsuya Hashimoto2,
Hiroyuki Kobayashi2,
Toyofumi Fukuda2,
Koji Okino3,
Noriyuki Yamamoto2,
Chikako Mashida4,
Kiyotaka Kawagoe4,
Hiroshi Fujita5,
Naoto Inoue5,
Hakuo Takahashi6 and
Toshihiko Ono2
1 Cardiovascular Division, 2 Division of Urology, and 3 Division of Surgery, Toujinkai Hospital, 5 Department of Interventional Cardiology, Kyoto Second Red Cross Hospital, Kyoto, 4 Pharmaceutical Research Laboratory, Hitachi Chemical Company, Ibaraki and 6 Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, Moriguchi, Japan
Correspondence and offprint requests to: Masato Nishimura, MD, Cardiovascular Division, Toujinkai Hospital, 16 Negoro, Momoyama-cho, Fushimi-ku, Kyoto, 612-8024 Japan. Email: mnishimura{at}tea.ocn.ne.jp
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Abstract
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Background. Traditional risk factors of cardiovascular disease do not fully explain the accelerated atherosclerosis present in patients with end-stage renal disease (ESRD). The goal of this study was to identify the association of clinical and laboratory factors including seropositivity for Chlamydia pneumoniae determined by a specific enzyme-linked immunosorbent assay (ELISA) with the presence of coronary artery disease identified by coronary angiography in ESRD patients.
Methods. We prospectively enrolled 161 consecutive ESRD patients undergoing haemodialysis for >6 months (106 men, 55 women; mean age 63.1±10.2 years; mean dialysis duration 91.3±90.1 months). All patients underwent coronary angiography within 1 week after blood sampling. The associations of coronary artery disease with clinical parameters including C. pneumoniae IgA and IgG seropositivity were analysed using multiple logistic regression models.
Results. Coronary stenosis >50% was found in 102 of 161 haemodialysis patients (63.4%). Of the 102 patients, 75.5% were asymptomatic. Seropositivity for C. pneumoniae IgA was found in patients with coronary stenosis (77 out of 102, 75.5%) more frequently (P<0.001) than in patients without coronary stenosis (10 out of 59, 16.9%). Seropositivity for C. pneumoniae IgA but not IgG was strongly associated with the presence of coronary stenosis in multiple logistic regression analysis (odds ratio, 18.440; 95% confidence interval, 7.50045.337), independently of the Framingham coronary risk factors, factors peculiar to ESRD or serum C-reactive protein levels.
Conclusions. C. pneumoniae IgA seropositivity determined by ELISA is an independent laboratory factor indicating the presence of coronary artery stenosis in ESRD patients undergoing maintenance haemodialysis.
Keywords: Chlamydia pneumoniae; coronary artery disease; ELISA; end-stage renal disease; haemodialysis; IgA
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Introduction
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Progression of systemic atherosclerosis is accelerated in patients with end-stage renal disease (ESRD) [1]. Cardiovascular disease is the leading cause of mortality in ESRD patients, and the prevalence of coronary artery disease in ESRD patients is high, ranging from 73% in the chronic haemodialysis population [2] to 85% in diabetic uraemic patients [3]. In our recent study [4], the incidence of significant coronary artery stenosis
75% determined by AHA classification was >70% in maintenance haemodialysis patients. On the other hand, traditional risk factors of cardiovascular disease such as hypertension, smoking or hypercholesterolaemia do not fully explain the accelerated atherosclerosis present in ESRD patients [5]. Of emerging cardiovascular risk factors, systemic inflammation is likely to contribute significantly to the initiation and progression of the atherosclerotic process in ESRD patients [6,7]. The infection-based atherogenous hypothesis could explain accelerated atherosclerosis and increased inflammation in ESRD patients. Many studies have suggested a possible association between C. pneumoniae infection and atherosclerotic diseases and/or inflammation in patients with chronic renal failure, and Song et al. [8] reported possible involvement of C. pneumoniae infection in coronary artery disease in chronic renal failure patients. On the other hand, Zoccali et al. [9] have shown recently that the more careful adjustment for other risk factors of cardiovascular diseases weakens the correlations between C. pneumoniae and atherosclerosis in patients with chronic renal failure. In the present study, we aimed to determine whether C. pneumoniae seropositivity, which was determined by a specific enzyme-linked immunosorbent assay (ELISA), was associated with the presence of coronary artery stenosis identified by coronary angiography (CAG) in chronic haemodialysis patients, independently of traditional coronary risk factors or factors peculiar to ESRD.
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Subjects and methods
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Patients
We prospectively enrolled 161 ESRD patients undergoing maintenance haemodialysis for >6 months at Toujinkai Hospital [106 men, 55 women; mean age 63.1±10.2 years; mean dialysis duration 91.3±90.1 months (7424 months)]. Patients diagnosed with acute or old myocardial infarction, idiopathic hypertrophic or dilated cardiomyopathy, or congestive heart failure (New York Heart Association grades IIIIV) were excluded. In addition, patients who had shown serum C-reactive protein (CRP) concentrations >10 µg/ml in four measurements were excluded from this study to remove the possibility of acute C. pneumoniae infection. Of the 161 patients, 75 had diabetes mellitus (47%), and 30 of the 75 diabetic patients had been receiving insulin therapy. Blood pressure was measured hourly during dialysis using a mercury sphygmomanometer; for study purposes, it was determined as the mean of the measurements obtained at eight different midweek haemodialysis sessions before CAG. Haemodialysis was performed three times weekly using a dialysate containing Na+ (140 mEq/l), K+ (2.0 mEq/l), Cl (110 mEq/l), Ca2+ (3.0 mEq/l), Mg2+ (1.0 mEq/l), HCO3 (30 mEq/l) and CH3COO (1015 mEq/l). The membranes used in the dialyser were cellulose triacetate (FB-190F, NIPRO, Tokyo, Japan), surface-modified regenerated cellulose (AMBC-20X, Asahi Medical, Tokyo, Japan), polymethyl methacrylate (FB-2.1F, TORAY Medical, Tokyo, Japan) or polysulfone (PS-1.9UW, Kawasumi Laboratory, Tokyo, Japan). The dialysis filter surface areas were 1.82.1 m2. Histories of cigarette smoking or alcohol consumption were ascertained by questionnaire. Smoking habit means
10 cigarettes per week. Alcohol consumption means intake of alcohol of
20 g per week. The Ethical Committee for Human Research of Toujinkai Hospital approved this study, and all patients provided informed consent prior to participation.
Coronary angiography (CAG)
All patients underwent CAG at the Department of Interventional Cardiology of the Kyoto Second Red Cross Hospital within 1 week after blood sampling and echocardiography. Quantitative CAG analysis was performed using a validated automated edge-detection program (CCIP-310/W, CATHEX, Tokyo, Japan), and luminal stenosis >50% was defined as a significant lesion.
Echocardiographic measurements
A two-dimensionally guided M-mode echocardiogram was obtained for each patient using a single ultrasonographic recorder (UF-8800, Fukuda Denshi, Tokyo, Japan) on a midweek non-dialysis day within 1 week before CAG. Measurements for M-mode-guided calculation of left ventricular mass (LVM), left ventricular internal end-diastolic and end-systolic dimensions (LVIDd and LVIDs), interventricular septal wall thickness (IVST) and left ventricular posterior wall thickness (PWT) were obtained according to the guidelines of the American Society of Echocardiography [10]. LVM was calculated according to the formula described by Devereux et al. [11] LVM (g/m2) = 1.04 [(LVIDd + IVST + PWT)3 LVIDd3] 13.6 g. LVM was normalized to body surface area and is reported as the LVM index (LVMI). The M-mode criteria for left ventricular hypertrophy (LVH) were >134 g/m2 body surface area in men or >110 g/m2 body surface area in women [10].
Biochemical and haematological determinations
Blood samples (5 ml) were obtained at the initiation of a mid-week haemodialysis, after the patient had been in the supine position for at least 10 min. Haematocrit and serum concentrations of haemoglobin, calcium and inorganic phosphorus were determined as the mean of eight different measurements within a 4 month period before the CAG. Serum calcium concentrations were corrected by serum albumin concentrations. Serum concentrations of total protein, albumin, total cholesterol, intact parathyroid hormone (iPTH) and CRP were determined as the mean of four different measurements within a 4 month period before the CAG. Plasma iPTH was measured using a chemiluminescent assay (Chemiluminescence Intact PTH 100T kit, Nichols Institute Diagnostics, San Juan Capistrano, CA). Serum CRP concentration was measured using a high sensitive assay kit (N-Assay LA CRP-S, D-type, Nittobo, Tokyo, Japan); the intra- and inter-assay coefficients of variation for this assay ranged from 0.6 to 1.6% and from 0.7 to 2.1%, respectively.
Serological study of C. pneumoniae infection
The concentrations of serum IgA and IgG antibodies against C. pneumoniae within 1 week before CAG were determined using a specific ELISA kit (HITAZYME C. pneumoniae, Hitachi Chemical, Tokyo, Japan) [12,13]. This ELISA method detects antibodies to the chlamydial outer membrane complex, which was isolated from purified elementary bodies of the C. pneumoniae YK-41 strain [14]. The concentrations of IgA and IgG antibodies against C. pneumoniae in each sample are expressed as the IgA or IgG index. The IgA index was determined by calculating the corrected optical density (OD) (405 nm) of the IgA sample divided by the IgA cut-off value, and the IgG index by calculating the corrected OD (405 nm) of the IgG sample divided by the IgG cut-off value. The corrected OD (405 nm) of a sample = the sample's OD (405 nm) x the reference value of the positive control/mean OD (405 nm) of the positive control. The cut-off value = mean OD (405 nm) of the negative control x the reference value of the positive control/the mean OD (405 nm) of the positive control + 0.20. Index values >1.10 are defined as positive for IgA or IgG antibodies, whereas values
1.10 are defined as negative [12,13]. Detection rates of IgG and IgA antibodies against C. pneumoniae using this ELISA method were compared with the microimmunofluorescence method: the sensitivity was 90.4% for detecting IgG and 84.6% for detecting IgA, and the specificity was 89.9% for detecting IgG and 86.7% for detecting IgA [12]. The rates of agreement between the ELISA method and western blotting analysis were 80.0% for IgG and 87.5% for IgA [13].
Statistical analysis
Values are expressed as the mean±SD. Differences in continuous variables between groups were evaluated by Wilcoxon rank-sum test, and differences in categorical data between groups were evaluated by
2 test. The associations of continuous or categorical data with coronary artery disease were analysed using multiple logistic regression models, with a dichotomous response variable used for the presence/absence of coronary artery disease and using backward elimination and forward selection procedures. Variables with independent association with the presence of significant coronary stenosis were identified by constructing hierarchical models, which included Framingham risk factors (age, gender, smoking, diabetes mellitus, systolic blood pressure, serum total cholesterol levels and LVH), clinical laboratory factors peculiar to ESRD (serum haemoglobin levels, albumin levels, calcium x phosphate product values and duration of haemodialysis) and a clinical laboratory factor relating to inflammation (serum CRP concentration). As a measure of the relative risk for the presence of coronary artery disease, the odds ratio (OR) and 95% confidence intervals (CIs) were calculated in order to summarize the effects of each covariate. All statistical tests were two-sided, with a value for P of <0.05 considered significant. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive potential of C. pneumoniae IgA or IgG index and serum CRP concentration for the presence of significant coronary stenosis [15]. The Statistical Analysis Software (SPSS for Windows, version 9.0J and 11.0J, Chicago, IL) system was used for statistical analyses.
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Results
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CAG findings
Significant coronary stenosis >50% was found in 102 of 161 haemodialysis patients (63.4%). Of the 102 subjects, single, double and triple vessel disease was present in 39, 34 and 24 patients, respectively. Stenosis of the left main trunk was present in five patients. Significant coronary stenosis >50% in the right coronary artery, left anterior descending artery or left circumflex artery was present in 59, 67 and 62 patients, respectively. Of the 102 patients who had coronary stenosis, 77 had not noted chest pain or discomfort before CAG (75.5%). The mean age (65.0±9.1 vs 59.9±11.3 years, P<0.01), the presence of diabetes mellitus [53.9% (55 out of 102) vs 35.6% (21 out of 59), P<0.05] and serum CRP concentration (4.76±3.75 vs 3.61±2.99 µg/ml, P<0.05) were greater in patients with coronary artery stenosis (n = 102) than in those without (n = 59). Diastolic blood pressure before dialysis (73±12 vs 77±9 mmHg, P<0.05), alcohol consumption (39.2 vs 59.3%, P<0.05), haematocrit (31.8±2.4 vs 32.9±3.0%, P<0.05), serum concentrations of haemoglobin (101.9±8.2 vs 105.4±9.0 g/l, P<0.05) and inorganic phosphorus (1.65±0.23 vs 1.74±0.23 mmol/l, P<0.05) were lower in patients with coronary artery stenosis (n = 102) than in those without (n = 59). Male gender [69 out of 102 (67.6%) vs 38 out of 59 (64.4%)], dialysis duration (84±87 vs 103±95 months), smoking habit (42.2 vs 45.8%), body mass index (20.8±2.9 vs 21.4±3.5 kg/m2), systolic blood pressure before dialysis (146±16 vs 148±16 mmHg) or after dialysis (136±18 vs 132±19 mmHg), cardiothoracic ratio (51.9±5.1 vs 50.8±4.3%), echocardiographic parameters (LVIDd, 51.2±6.9 vs 50.8±7.8 mm; LVIDs, 34.5±8.2 vs 33.0±7.1 mm; LVFS, 33.2±9.9 vs 36.1±9.2%; LVEF, 60.7±14.7 vs 64.4±12.0%; IVST, 11.7±3.2 vs 11.4±3.1 mm; PWT, 9.2±2.1 vs 9.6±1.7; LVMI, 152±57 vs 151±58 g/m2), serum concentrations of albumin (37.3±3.4 vs 38.2±2.7 g/l), total cholesterol (4.33±0.91 vs 4.14±0.75 mmol/l) or iPTH (281±263 vs 258±210 pg/ml) and calcium phosphate (3.82±0.03 vs 3.94±0.42 mmol2/l2) did not differ between patients with coronary stenosis (n = 102) and those without coronary stenosis (n = 59). The frequencies of use of the drugs which may affect the cardiovascular system did not differ between patients with coronary stenosis (n = 102) and those without coronary stenosis (n = 59): patients with coronary stenosis, calcium blockers 33%, angiotensin-converting enzyme inhibitors 7%, angiotensin II receptor blockers 9%, ß-blockers 8%,
1 receptor blockers 11%, anti-platelet drugs 33% and statins 4%; patients without coronary stenosis, calcium blockers 34%, angiotensin-converting enzyme inhibitors 8%, angiotensin II receptor blockers 8%, ß-blockers 7%,
1 receptor blockers 10%, anti-platelet drugs 32% and statins 4%.
Serological study of C. pneumoniae
Seropositivity for C. pneumoniae IgA was found in 54.1% of all of the haemodialysis patients (87 out of 161). It was recognized in 77 of 102 patients with coronary artery stenosis (75.5%) and in 10 of 59 patients without coronary stenosis (16.9%; P<0.001). Seropositivity for C. pneumoniae IgG was found in 56.5% of all of the haemodialysis patients (91 out of 161). It was recognized in 67 of 102 patients with coronary artery disease (65.7%) and in 24 of 59 patients without coronary disease (40.7%; P<0.01). The mean IgA and IgG indices for C. pneumoniae were greater in patients with coronary stenosis than in those without [IgA, 1.846±0.982 (n = 102) vs 0.671±0.402 (n = 59), P = 0.0001; IgG, 1.537±0.847 vs 0.968±0.758, P = 0.0001]. The percentage of C. pneumoniae IgA seropositivity did not differ between diabetic and non-diabetic patients [60.5±51.8% (n = 76) vs 48.2±50.3% (n = 85)], and between patients with and without alcohol consumption [52.0±52.9% (n = 75) vs 55.8±50.0% (n = 86)]. The C. pneumoniae IgA index did not correlate significantly with age (r = 0.118, P = 0.109, n = 161), serum CRP concentration (r = 0.121, P = 0.103, n = 161) and serum concentration of inorganic phosphorus (r = 0.111, P = 0.160, n = 161).
Factors associated with the presence of coronary artery stenosis
In multiple logistic regression analysis including Framingham coronary risk factors (including echocardiographically detected LVH), clinical laboratory factors peculiar to ESRD (serum levels of haemoglobin, albumin or calcium phosphate, and dialysis duration) and serum CRP levels, the presence of coronary artery stenosis >50% was significantly associated with diabetes mellitus (OR, 2.496; 95% CI, 1.2005.193; P = 0.014), age (OR, 1.052; 95% CI, 1.0121.093; P = 0.010) and serum CRP concentration (OR, 1.115; 95% CI, 1.0081.236; P = 0.049) when C. pneumoniae IgA seropositivity was not included in the analysis. However, when C. pneumoniae IgA seropositivity was included in the multiple logistic regression analysis, C. pneumoniae IgA seropositivity was strongly associated with the presence of coronary artery stenosis not only in all of the coronary arteries but also in the right coronary, left anterior descending or left circumflex arteries individually (Table 1). In contrast, diastolic blood pressure before dialysis and alcohol consumption were inversely associated with the presence of coronary artery stenosis. The presence of diabetes mellitus was related to the presence of lesions in the left anterior descending artery, and the serum haemoglobin concentration was inversely related to the presence of lesions in the left circumflex artery. Other factors including age, blood pressure, smoking, haemodialysis duration and serum concentrations of total cholesterol or CRP were not selected in the logistic models. Furthermore, the significant association of C. pneumoniae IgA seropositivity with the presence of coronary artery stenosis remained almost unchanged after adjustment for Framingham risk factors, clinical factors peculiar to ESRD and serum CRP levels (Table 2).
Coronary plaques and C. pneumoniae IgA
We identified 272 plaques that had coronary stenosis >50% in the coronary arteries of 102 haemodialysis patients. The mean number of total coronary plaques of which coronary stenosis was >50% was greater in patients with C. pneumoniae IgA seropositivity than those without [2.88±1.75 (n = 77) vs 2.04±1.48 (n = 25), P = 0.033], and the C. pneumoniae IgA index correlated positively with the numbers of the total coronary plaques of which stenosis was >50% (r = 0.196, P = 0.048, n = 102). Further, we identified 430 plaques that had coronary stenosis >25% in the coronary arteries of 113 haemodialysis patients. The mean number of total coronary plaques of which stenosis was >25% was also greater in patients with C. pneumoniae IgA seropositivity than those without [4.44±2.66 (n = 77) vs 2.44±1.96 (n = 36), P = 0.001], and the C. pneumoniae IgA index correlated positively with the numbers of the total coronary plaques of which stenosis was >25% (r = 0.291, P = 0.002, n = 113).
ROC analysis
ROC analysis indicated that the IgA index for C. pneumoniae was predictive of the presence of coronary artery stenosis more strongly than the C. pneumoniae IgG index or serum CRP concentration (Figure 1). The area under the curve was 0.854 for the IgA index, 0.709 for the IgG index and 0.584 for the serum CRP concentration.

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Fig. 1. Receiver operating characteristic (ROC) curves indicating the diagnostic potential for coronary artery stenosis for Chlamydia pneumoniae IgA, IgG or serum C-reactive protein (CRP) concentration. The area under the curve (AUC) was 0.854 for IgA, 0.709 for IgG and 0.584 for CRP.
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Discussion
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In the present study, seropositivity for C. pneumoniae IgA was found in 75.5% of patients with coronary artery stenosis, whereas it was seen in only 16.9% of patients without coronary stenosis. On the other hand, seropositivity for C. pneumoniae IgG was found in 65.7% of patients with coronary stenosis and in 40.7% of patients without coronary stenosis. Multivariate analysis using logistic models indicated that C. pneumoniae IgA seropositivity was strongly associated with the presence of coronary artery stenosis in haemodialysis patients (OR = 18.440). This significant association between C. pneumoniae IgA seropositivity and coronary stenosis in haemodialysis patients was not affected by Framingham coronary risk factors, clinical factors peculiar to ESRD and serum CRP concentration. In contrast, seropositivity for C. pneumoniae IgG was not associated with coronary artery stenosis. ROC analysis indicated that the C. pneumoniae IgA index was related to the presence of coronary artery stenosis more strongly than the C. pneumoniae IgG index or serum CRP concentration. Since IgA has a short half-life of 57 days and the cases where acute infection was suspected were excluded from this study, the presence of serum IgA antibody in this study is thought to mean the persistent infection of C. pneumoniae, although serological study for C. pneumoniae antibodies was performed once. The results of this study indicate the close and independent association between chronic C. pneumoniae infection and the presence of significant coronary stenosis in maintenance haemodialysis patients. In the present study, the mean number of total coronary plaques was greater in patients with C. pneumoniae IgA seropositivity than in those without in haemodialysis patients who had significant coronary stenosis. Furthermore, the number of total coronary plaques positively correlated with the C. pneumoniae IgA index in haemodialysis patients with coronary stenosis. Thus, C. pneumoniae IgA seropositivity by ELISA, which is thought to indicate chronic C. pneumoniae infection, may be involved in the progression of coronary atherosclerosis in haemodialysis patients.
Independent cardiovascular risk factors such as age, diabetes mellitus, high CRP levels and low alcohol consumption were more prevalent in patients with coronary stenosis than in those without coronary stenosis. On the other hand, the C. pneumoniae IgA index did not significantly correlate with age or serum CRP concentration, and the percentage C. pneumoniae IgA seropositivity did not differ between diabetic and non-diabetic patients and between patients with and without alcohol consumption. Therefore, it would not be conceivable that the group with coronary stenosis had higher C. pneumoniae IgA titres or seropositivity than the group without coronary stenosis because of increased age or serum CRP concentration, increased numbers with diabetes mellitus or low alcohol consumption. Further, since these risk factors did not affect the close association between C. pneumoniae IgA seropositivity and coronary stenosis in haemodialysis patients, we do not think that increased age, increased number of diabetics, high CRP levels and low alcohol consumption in the group of coronary stenosis may reduce the predictive value of C. pneumoniae IgA seropositivity for coronary artery disease in haemodialysis patients.
Elevated circulating levels of inorganic phosphorus could be involved in progressive cardiovascular calcified atherosclerosis of patients with chronic renal failure [16,17]. In this study, the mean serum concentration of inorganic phosphorus was lower in patients with coronary stenosis than in those without. However, our data do not deny the role of serum phosphorus concentration in calcified atherosclerosis in ESRD patients. Although we did not evaluate the extent of vascular calcification, the serum phosphorus concentration may be involved in the coronary calcification rather than in the coronary atherosclerosis itself. We need further investigation to clarify the relationship among calcified coronary atherosclerosis, circulating phosphorus concentration and C. pneumoniae infection.
We used an ELISA method, but not microimmunofluorescence, to measure IgA and IgG antibodies against C. pneumoniae. Microimmunofluorescence is the recommended method for detection of C. pneumoniae antibodies [18], and has been used in most clinical studies. However, this method requires skilled personnel for interpretation of the slides. Further, the specificity of the microimmunofluorescence method has been questioned, as cross-reactions among the major outer membrane proteins of different Chlamydia species were reported [19,20]. On the other hand, ELISA has been recognized as an unreliable method for C. pneumoniae identification compared with microimmunofluorescence. However, ELISA is relatively simple to perform, and is more objective than microimmunofluorescence because of the photometrical reading of the results. In the ELISA used in our study, the sensitivity was 90.4% for detecting IgG and 84.6% for detecting IgA, and the specificity was 89.9% for detecting IgG and 86.7% for detecting IgA using the microimmunofluorescence method as the reference [12]. In addition, the rates of agreement between ELISA and western blotting analysis were 80.0% for IgG and 87.5% for IgA [13]. Hoymans et al. [21] have recently reported that the sandwich ELISA, which is the same as our method, shows good agreement with the microimmunofluorescence method. The ELISA used in this study is believed to have a sufficiently good performance to detect circulating antibodies against C. pneumoniae.
The point that we would like to emphasize in this study is that C. pneumoniae IgA seropositivity determined by ELISA may be an important clinical laboratory factor strongly indicating the presence of coronary artery stenosis in haemodialysis patients, independently of Framingham risk factors, clinical laboratory factors peculiar to ESRD and serum CRP levels. Considering that the duration of haemodialysis dependence was extremely variable in the subjects of the present study, and that the presence of coronary artery stenosis was not related to the haemodialysis duration, this association between C. pneumoniae IgA seropositivity and coronary artery disease could be applicable not only to chronic haemodialysis patients but also to ESRD patients before the start of haemodialysis. Chlamydia pneumoniae IgA seropositivity determined by ELISA may be useful for predicting the presence of coronary artery lesions in chronic haemodialysis patients, who have a high incidence of asymptomatic coronary artery disease [4].
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Acknowledgments
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The authors greatly appreciate the assistance of the staff of the Department of Interventional Cardiology at the Kyoto Second Red Cross Hospital with coronary angiography.
Conflict of interest statement. None declared.
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Received for publication: 29.11.04
Accepted in revised form: 20. 4.05