Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Palikhe, A. Articles by Sinisalo, J. Search for Related Content PubMed PubMed Citation Articles by Palikhe, A. Articles by Sinisalo, J.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, January 2008, p. 55-59, Vol. 15, No. 1
1071-412X/08/$08.00+0     doi:10.1128/CVI.00163-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Association of Chlamydia pneumoniae Infection with HLA-B*35 in Patients with Coronary Artery Disease

Anil Palikhe,^1,2 Marja-Liisa Lokki,² Pekka Saikku,³ Maija Leinonen,⁴ Mika Paldanius,⁴ Mikko Seppänen,⁵ Ville Valtonen,⁵ Markku S. Nieminen,¹ and Juha Sinisalo^1*

Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland,¹ Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland,² Department of Medical Microbiology, University of Oulu, Oulu, Finland,³ National Public Health Institute, Oulu, Finland,⁴ Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland⁵

Received 30 March 2007/ Returned for modification 16 July 2007/ Accepted 24 October 2007

Top ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
The immune system may interplay between Chlamydia pneumoniae infection and coronary artery disease (CAD). Major histocompatibility complex genes regulate innate and adaptive immunity. Patients with CAD (n = 100) and controls (n = 74) were enrolled. Human leukocyte antigens (HLA-A, HLA-B, and HLA-DRB1), four lymphotoxin alpha single-nucleotide polymorphisms, and complement C4A and C4B allotypes were typed, and their haplotypes were inferred. The presence of serum C. pneumoniae immunoglobulin A (IgA) (titer, 40) or IgG (titer, 128) antibodies or immune complex (IC)-bound IgG antibodies (titer, 2) was considered to be a serological marker suggesting chronic C. pneumoniae infection. C. pneumoniae IgA antibodies were found more frequently in patients than in controls (P = 0.04). Among the patients, multiple logistic regression analysis showed the HLA-B*35 allele to be the strongest-risk gene for C. pneumoniae infection (odds ratio, 7.88; 95% confidence interval, 2.44 to 25.43; P = 0.0006). Markers of C. pneumoniae infection were found more frequently in patients with the HLA-A*03-B*35 haplotype than in those without the haplotype (P = 0.007 for IgA; P = 0.008 for IgG; P = 0.002 for IC). Smokers with HLA-B*35 or HLA-A*03-B*35 had markers of C. pneumoniae infection that appeared more often than in smokers without these genes (P = 0.003 and P = 0.001, respectively). No associations were found in controls. In conclusion, HLA-B*35 may be the link between chronic C. pneumoniae infection and CAD.

Top ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Atherosclerosis is a chronic inflammatory process (11) in which infections, especially those caused by Chlamydia pneumoniae (24, 35), have been suggested to play a role. C. pneumoniae is a common cause of respiratory tract infections. Like all chlamydial species, it has a tendency to cause chronic infections. This may lead to severe sequelae such as chronic obstructive pulmonary disease (42) and cardiovascular diseases (24). Most likely, all individuals get infected with C. pneumoniae during their lifetimes, but many of them are capable of resolving the infection, and only some become chronically infected. It is assumed that in order to maintain a persistent infection and to evade host defense mechanisms, chlamydiae have developed specific strategies (9), e.g., by being an obligatory intracellular organism and by having a unique and complicated life cycle (21). An aberrant and persistent form of C. pneumoniae can be induced by gamma interferon (31), antibiotics (7), and tobacco smoke (44) in in vitro cell cultures. In vivo, however, immunogenetic factors (22) of the host also contribute to the infection outcome.

The major histocompatibility complex (MHC) region takes part in innate and adaptive immunity (28). MHC molecules present microbial peptides to the appropriate subsets of T cells. Patients with specific HLA genes are susceptible or resistant to certain viral and nonviral pathogens (12, 32). Immunoglobulin A (IgA) and IgG antibodies against C. pneumoniae (35) and immune complexes (ICs) (23, 25) have frequently been found to be present in sera of patients with coronary artery disease (CAD). Recently, we showed that HLA-B*35- and DRB1*01-related haplotypes are found more frequently in patients with CAD than in healthy age- and sex-matched controls. Also, smokers who had a complement component C4B null allele together with HLA-DRB1*01 were shown to be prone to cardiovascular disease (30). Therefore, in this study, we assessed MHC genes associated with serological markers of C. pneumoniae infection, elevated specific IgA and IgG antibody levels and the presence of specific circulating ICs, in patients with CAD.

Top ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Study subjects. Patients with CAD (n = 148) were recruited from nine different central hospitals in Finland between September 1998 and December 2000, as described previously (39). The inclusion criteria for the patients were as follows. Patients had to have clear symptoms of angina with electrocardiographic evidence of myocardial ischemia. Patients who met the anginal pain inclusion criteria but none of the electrocardiographic criteria were eligible to enter the trial if their cardiac enzymes were consistent with the occurrence of myocardial infarction. Patients with prolonged chest pain with electrocardiogram changes indicating either unstable angina (n = 43) or non-Q-wave myocardial infarction (n = 105) were enrolled. No differences in the C. pneumoniae infection markers between the patients with unstable angina and non-Q myocardial infarction were found (data not shown). The original study was a placebo-controlled study on clarithromycin treatment of patients with acute coronary syndrome (ACS) (39). For the MHC gene study, we randomly selected 100 of the patients. No differences in the C. pneumoniae infection markers studied were found between the patients receiving study medication and placebo (data not shown). Blood samples from patients were taken at the time of hospitalization (visit 1) and 1 week (visit 2), 3 months (visit 3), and 1 year (visit 4) after hospital admission. Consecutive age- and sex-matched healthy blood donors (n = 74) served as controls and donated a blood sample once. The criteria for blood donation are available at http://www.veripalvelu.redcross.fi/.

Baseline characteristics of the patients and controls are shown in Table 1. All patients and controls gave written informed consent. Study protocols were approved by local ethics committees.

View this table: [in this window] [in a new window]

TABLE 1. Characteristics of patients with ACS and controls

Laboratory procedures. Genomic HLA-A, HLA-B, and HLA-DRB1 tissue typing, four lymphotoxin alpha (LTA) single-nucleotide polymorphisms (positions +253 [a/g], +496 [C/T], +633 [c/g], and +724 [C/A]), and complement C4A and C4B allotyping were performed (lowercase indicates intronic and uppercase indicates exonic variation). MHC haplotypes of the subjects were inferred using all these markers (30).

Sera were tested for C. pneumoniae-specific IgA and IgG antibodies by the microimmunofluorescence method using elementary bodies of Kajaani 6 as antigens (43). Fourfold serum dilutions were used, starting from 1/32 for IgG and 1/10 for IgA, as described previously (13, 14). Isolation of C. pneumoniae-specific ICs was performed by polyethylene glycol precipitation, and IgG antibodies against C. pneumoniae were measured from dissociated ICs by microimmunofluorescence at twofold dilutions starting from a dilution of 1/2, as described previously (13, 25).

Due to the lack of information on controls’ smoking statuses, we measured plasma cotinine levels by use of a gas chromatograph equipped with a nitrogen phosphorous detector. The cutoff point for the classification of active smoking was set at 10 ng/ml (1), revealing subjects who had smoked tobacco within a week.

Statistical analysis. For this study, elevated levels of antichlamydial IgA (titer, 40) or IgG (titer, 128) or the presence of IC-bound antichlamydial IgG antibodies (titer, 2) at any visit was considered to be a marker of C. pneumoniae infection, suggesting persistent infection (14). Positivity with any of these three titers was considered to be positivity for C. pneumoniae infection. The correlation between C. pneumoniae infection and CAD was examined by comparing C. pneumoniae infection markers in patients and controls. The potential association between MHC genes and C. pneumoniae infection markers was examined as follows.

Forward stepwise multiple-logistic regression analysis was used to study the association between alleles (HLA-A, HLA-B, LTA+253a/g, LTA+496C/T, LTA+633c/g, LTA+724C/A, C4A, C4B, and HLA-DRB1) and any of the markers of C. pneumoniae infection. Categorical data were compared by the chi-square or Fisher's exact test to study whether the frequencies of C. pneumoniae infection markers differed in patients with and those without the MHC alleles.

Data were analyzed using SPSS 12.0.1 (SPSS Inc., Chicago, IL). For all statistical tests, a P value of <0.05 was considered to be statistically significant.

Top ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Baseline characteristics of patients with ACS (n = 100) and controls (n = 74) are shown in Table 1. C. pneumoniae titers for both patients and controls ranged between 5 and 640 for IgA, 16 and 2,048 for IgG, and 1 and 32 for IC. Patients were C. pneumoniae seropositive more often than controls (Table 2).

View this table: [in this window] [in a new window]

TABLE 2. C. pneumoniae markers, gender, and smoking status in patients with ACS (n = 100) and controls (n = 74)a

In univariate analyses, any single marker (IgA titer of 40, IgG titer of 128, or IC titer of 2) of C. pneumoniae infection was found more frequently in the patients with the haplotypes HLA-A*03-B*35 and HLA-A*03-B*35-LTA+724C than in patients without these haplotypes (Table 3). Also, any of the markers of C. pneumoniae infection were found significantly more frequently in patients with the HLA-A*03-B*35 or the HLA-A*03-B*35-LTA+724C haplotype than in patients with the HLA-DRB1*01 allele (P = 0.044 and P = 0.048, respectively). In subgroup analyses, when gender and smoking were also considered, any of the markers of C. pneumoniae infection were significantly associated with males having the HLA-A*03-B*35 (P = 0.008) or HLA-A*03-B*35-LTA+724C (P = 0.02) haplotype as well as with current smokers with these haplotypes or the HLA-B*35 allele alone (P = 0.001, P = 0.009, and P = 0.003, respectively) (Table 4). Among the controls, no associations between C. pneumoniae markers and MHC genes (Table 3), smoking status, or gender were found.

View this table: [in this window] [in a new window]

TABLE 3. Significant association of MHC genes and haplotypes with a single marker of C. pneumoniae infections in patients with ACSa

View this table: [in this window] [in a new window]

TABLE 4. Significant correlations between any of the markers of C. pneumoniae infection and the known risk factors for C. pneumoniae infection in patients with ACSa

In multiple-logistic regression analysis, any of the markers of C. pneumoniae infection were associated with HLA-B*35 (odds ratio [OR], 7.88; 95% confidence interval [CI], 2.44 to 25.43; P = 0.0006) as well as with HLA-A*02 (OR, 4.15; 95% CI, 1.42 to 12.10; P = 0.009) and C4B2 (OR, 3.60; 95% CI, 1.19 to 10.86; P = 0.02). However, the latter two did not associate in univariate analyses.

Top ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
This study shows for the first time that markers of C. pneumoniae infection are associated with HLA-B*35-related haplotypes in patients with ACS. Furthermore, among these patients, the prevalence of C. pneumoniae infection markers was more pronounced in smokers and males. In the controls, HLA-B*35 was not associated with C. pneumoniae infection. HLA-B*35 alone or together with the other functionally important genes on the A*03-B*35-LTA+724C haplotype may provide one possible link between CAD and C. pneumoniae infection.

C. pneumoniae infection has been linked to CAD by several methodological approaches, e.g., by seroepidemiological studies and by demonstrating the presence of C. pneumoniae in atherosclerotic lesions by culture, immunocytochemistry, PCR, and electron microscopy. In the present study, we used elevated antichlamydial IgA, IgG, and ICs as markers of chronic C. pneumoniae infection. Thus, antibodies are only indirect evidence of chronic Chlamydia infection; however, IC and IgA levels will not stay high without a continuous infection (25, 36). The prevalence of these markers was lower than that reported previously (35) but significantly higher in patients than in controls. Smoking and male gender are established risk factors for CAD and also predispose one to C. pneumoniae infection (19, 22). Also, in this study, male gender and smoking, when related to HLA-B*35, were definite risk factors for C. pneumoniae infection in patients with CAD. When HLA-B*35 was absent, any of the markers of C. pneumoniae infection were almost threefold lower in current smokers. No such relation was found in controls. Thus, suggested chronic C. pneumoniae infection in patients with CAD seems to be the result of multiple factors, and among them, the HLA-B*35-positive haplotype may play an important role.

Associations between immunity and genes regulating inflammation with CAD and C. pneumoniae infection have been studied only occasionally (29, 34). Dahlén et al. (5) previously studied class II HLA genes and showed that C. pneumoniae antibodies and high Lp(a) levels were associated with HLA-DRB1*03 and HLA-DRB1*13, but the association was not later confirmed by the same group (5, 15). We have recently shown an association between CAD and HLA-B*35, DRB1*01-related haplotypes. The results in this study may indicate that the elevated markers of C. pneumoniae infection associate especially with the presence of the HLA-B*35 allele on the haplotype HLA-A*03-B*35-LTA+724C. Eighty- one percent of HLA-A*03-B*35 and HLA-A*03-B*35-LTA+724C haplotype-positive patients had any of the markers of C. pneumoniae infection, while on the contrary, 55% of HLA-DRB1*01-positive patients had any of the markers of C. pneumoniae infection.

Both the incidence of CAD (16, 17) and the prevalence of C. pneumoniae markers (18) are elevated in the eastern part of Finland. The HLA-B*35 allele is one of the most frequently isolated HLA alleles in the Finnish population and has an even higher prevalence in the eastern parts (40), suggesting an accessible association between CAD, C. pneumoniae, and the HLA-B*35 allele.

In addition to C. pneumoniae, an infectious etiology of atherosclerosis and CAD has been implicated with regard to Helicobacter pylori, herpes simplex virus, and cytomegalovirus (27). Several case control studies suggested that vaccination against influenza virus may reduce the risk of myocardial infarction (8, 26). One of the preferred alleles in the influenza A virus-specific cytotoxic-T-lymphocyte response is HLA-B*3501; preferential HLA usage is dependent on the type of the virus and determines differential cytokine expression (2, 3). The HLA-B*35 allele has also been associated with chronic hepatitis B virus, hepatitis C virus, and herpes simplex virus infections; Epstein-Barr virus seropositivity; and cytotoxic responses against Aspergillus and Mycobacterium tuberculosis (10, 20, 33, 45). In human immunodeficiency virus infection, the rapid progression of the disease has been correlated to the interaction of a virus peptide with B*35 (4). Recently, it has been shown that C. pneumoniae-infected host cells can induce genes involved in apoptosis (6), while HLA-B35 influences the apoptosis rate (37).

The results of our study indicate that HLA-B35 presents C. pneumoniae peptides and may further provide an environment that predetermines the establishment of persistent C. pneumoniae infection. The HLA-B*35 allele has been shown to confer a significant proapoptotic influence to different kind of cells. It may promote pathological cell activation and proliferation and gene transcription through the control of the intracellular cation concentration (38). C. pneumoniae-infected monocyte cells are shown to up-regulate many genes including the vasoconstrictor endothelin 1 (41). HLA-B*35 influences the upregulation of endothelin 1, providing an explanation for the epidemiological association existing between isolated pulmonary hypertension and HLA-B*35 (38).

In conclusion, our results show that the HLA-B*35-positive haplotypes confer a C. pneumoniae-related risk for CAD.

 
This study was funded by the University of Helsinki Foundation, Finnish-Norwegian Medical Foundation, Aarne Koskelo Foundation, Finnish Foundation for Cardiovascular Research, Special Governmental Subsidy for Health Sciences Research (EVO), Medical Research Fund of the Finnish Red Cross Blood Transfusion Service, and the Päivikki and Sakari Sohlberg Foundation.

M.-L.L. is employed by the Haartman Institute, University of Helsinki, and consults at HaartBio, a company owned by the University of Helsinki and which offers MHC typing services. No conflicts are reported for all other authors.

 
* Corresponding author. Mailing address: Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, P.O. Box 340, FI-00029 Helsinki, Finland. Phone: 358-9-471 72442. Fax: 358-9-471 74574. E-mail: juha.sinisalo{at}hus.fi

Published ahead of print on 7 November 2007.

Top ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

1
1. Benowitz, N. L., F. Kuyt, P. Jacob III, R. T. Jones, and A. L. Osman. 1983. Cotinine disposition and effects. Clin. Pharmacol. Ther. 34:604-611.[Medline]
2
2. Boon, A. C., G. De Mutsert, R. A. Fouchier, K. Sintnicolaas, A. D. Osterhaus, and G. F. Rimmelzwaan. 2004. Preferential HLA usage in the influenza virus-specific CTL response. J. Immunol. 172:4435-4443.[Abstract/Free Full Text]
3
3. Boon, A. C., G. de Mutsert, Y. M. Graus, R. A. Fouchier, K. Sintnicolaas, A. D. Osterhaus, and G. F. Rimmelzwaan. 2002. Sequence variation in a newly identified HLA-B35-restricted epitope in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. J. Virol. 76:2567-2572.[Abstract/Free Full Text]
4
4. Carrington, M., and S. J. O'Brien. 2003. The influence of HLA genotype on AIDS. Annu. Rev. Med. 54:535-551.[CrossRef][Medline]
5
5. Dahlén, G. H., J. Boman, L. S. Birgander, and B. Lindblom. 1995. Lp(a) lipoprotein, IgG, IgA and IgM antibodies to Chlamydia pneumoniae and HLA class II genotype in early coronary artery disease. Atherosclerosis 114:165-174.[CrossRef][Medline]
6
6. Eickhoff, M., J. Thalmann, S. Hess, M. Martin, T. Laue, J. Kruppa, G. Brandes, and A. Klos. 2007. Host cell responses to Chlamydia pneumoniae in gamma interferon-induced persistence overlap those of productive infection and are linked to genes involved in apoptosis, cell cycle, and metabolism. Infect. Immun. 75:2853-2863.[Abstract/Free Full Text]
7
7. Gieffers, J., J. Rupp, A. Gebert, W. Solbach, and M. Klinger. 2004. First-choice antibiotics at subinhibitory concentrations induce persistence of Chlamydia pneumoniae. Antimicrob. Agents Chemother. 48:1402-1405.[Abstract/Free Full Text]
8
8. Gurfinkel, E. P., R. Leon de la Fuente, O. Mendiz, and B. Mautner. 2004. Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) study. Eur. Heart. J. 25:25-31.[Abstract/Free Full Text]
9
9. Hackstadt, T. 2000. Redirection of host vesicle trafficking pathways by intracellular parasites. Traffic 1:93-99.[CrossRef][Medline]
10
10. Hammond, A. S., M. R. Klein, T. Corrah, A. Fox, A. Jaye, K. P. McAdam, and R. H. Brookes. 2005. Mycobacterium tuberculosis genome-wide screen exposes multiple CD8 T cell epitopes. Clin. Exp. Immunol. 140:109-116.[CrossRef][Medline]
11
11. Hansson, G. K. 2005. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352:1685-1695.[Free Full Text]
12
12. Hill, A. V. 1998. The immunogenetics of human infectious diseases. Annu. Rev. Immunol. 16:593-617.[CrossRef][Medline]
13
13. Huittinen, T., D. Hahn, T. Anttila, E. Wahlström, P. Saikku, and M. Leinonen. 2001. Host immune response to Chlamydia pneumoniae heat shock protein 60 is associated with asthma. Eur. Respir. J. 17:1078-1082.[Abstract/Free Full Text]
14
14. Huittinen, T., M. Leinonen, L. Tenkanen, H. Virkkunen, M. Manttari, T. Palosuo, V. Manninen, and P. Saikku. 2003. Synergistic effect of persistent Chlamydia pneumoniae infection, autoimmunity, and inflammation on coronary risk. Circulation 107:2566-2570.[Abstract/Free Full Text]
15
15. Jonasson, L., T. Eriksson, G. H. Dahlén, and B. Lindblom. 1997. Lipoprotein (a) and HLA-DRB1 and -DQB1 genes in coronary artery disease. Atherosclerosis 133:111-114.[CrossRef][Medline]
16
16. Jousilahti, P., E. Vartiainen, J. Pekkanen, J. Tuomilehto, J. Sundvall, and P. Puska. 1998. Serum cholesterol distribution and coronary heart disease risk: observations and predictions among middle-aged population in eastern Finland. Circulation 97:1087-1094.[Abstract/Free Full Text]
17
17. Jousilahti, P., E. Vartiainen, J. Tuomilehto, J. Pekkanen, and P. Puska. 1998. Role of known risk factors in explaining the difference in the risk of coronary heart disease between eastern and southwestern Finland. Ann. Med. 30:481-487.[Medline]
18
18. Karvonen, M., J. Tuomilehto, J. Pitkäniemi, A. Naukkarinen, and P. Saikku. 1994. Chlamydia pneumoniae IgG antibody prevalence in south-western and eastern Finland in 1982 and 1987. Int. J. Epidemiol. 23:176-184.[Abstract/Free Full Text]
19
19. Karvonen, M., J. Tuomilehto, J. Pitkäniemi, A. Naukkarinen, and P. Saikku. 1994. Importance of smoking for Chlamydia pneumoniae seropositivity. Int. J. Epidemiol. 23:1315-1321.[Abstract/Free Full Text]
20
20. Kim, J. H., C. W. Pyo, D. K. Koh, J. K. Hur, J. H. Kang, and T. G. Kim. 2006. Alteration of the influences of HLA classes I and II alleles on the perinatal hepatitis B virus infection after immunoprophylaxis in Korean children. Hepatol. Res. 35:118-126.[CrossRef][Medline]
21
21. Kuo, C. C., L. A. Jackson, L. A. Campbell, and J. T. Grayston. 1995. Chlamydia pneumoniae (TWAR). Clin. Microbiol. Rev. 8:451-461.[Abstract/Free Full Text]
22
22. Leinonen, M. 2000. Chlamydia pneumoniae and other risk factors for atherosclerosis. J. Infect. Dis. 181(Suppl. 3):S414-S416.[CrossRef][Medline]
23
23. Leinonen, M., E. Linnanmaki, K. Mattila, M. S. Nieminen, V. Valtonen, M. Leirisalo-Repo, and P. Saikku. 1990. Circulating immune complexes containing chlamydial lipopolysaccharide in acute myocardial infarction. Microb. Pathog. 9:67-73.[CrossRef][Medline]
24
24. Leinonen, M., and P. Saikku. 2002. Evidence for infectious agents in cardiovascular disease and atherosclerosis. Lancet Infect. Dis. 2:11-17.[CrossRef][Medline]
25
25. Linnanmäki, E., M. Leinonen, K. Mattila, M. S. Nieminen, V. Valtonen, and P. Saikku. 1993. Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease. Circulation 87:1130-1134.[Abstract/Free Full Text]
26
26. Madjid, M., M. Naghavi, S. Litovsky, and S. W. Casscells. 2003. Influenza and cardiovascular disease: a new opportunity for prevention and the need for further studies. Circulation 108:2730-2736.[Free Full Text]
27
27. Mehta, J. L., T. G. Saldeen, and K. Rand. 1998. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease. J. Am. Coll. Cardiol. 31:1217-1225.[Abstract/Free Full Text]
28
28. MHC Sequencing Consortium. 1999. Complete sequence and gene map of a human major histocompatibility complex. Nature 401:921-923.[CrossRef][Medline]
29
29. Momiyama, Y., R. Hirano, H. Taniguchi, H. Nakamura, and F. Ohsuzu. 2001. Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection. J. Am. Coll. Cardiol. 38:712-717.[Abstract/Free Full Text]
30
30. Palikhe, A., J. Sinisalo, M. Seppänen, V. Valtonen, M. S. Nieminen, and M. L. Lokki. 2007. Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease. Tissue Antigens 69:47-55.[CrossRef][Medline]
31
31. Pantoja, L. G., R. D. Miller, J. A. Ramirez, R. E. Molestina, and J. T. Summersgill. 2001. Characterization of Chlamydia pneumoniae persistence in HEp-2 cells treated with gamma interferon. Infect. Immun. 69:7927-7932.[Abstract/Free Full Text]
32
32. Petzl-Erler, M. L. 1999. Genetics of the immune responses and disease susceptibility. Ciência Cultura 51:1999-2011.
33
33. Ramadan, G., B. Davies, V. P. Kurup, and C. A. Keever-Taylor. 2005. Generation of cytotoxic T cell responses directed to human leucocyte antigen class I restricted epitopes from the Aspergillus f16 allergen. Clin. Exp. Immunol. 140:81-91.[CrossRef][Medline]
34
34. Rugonfalvi-Kiss, S., V. Endresz, H. O. Madsen, K. Burian, J. Duba, Z. Prohaszka, I. Karadi, L. Romics, E. Gonczol, G. Fust, and P. Garred. 2002. Association of Chlamydia pneumoniae with coronary artery disease and its progression is dependent on the modifying effect of mannose-binding lectin. Circulation 106:1071-1076.[Abstract/Free Full Text]
35
35. Saikku, P., M. Leinonen, K. Mattila, M. R. Ekman, M. S. Nieminen, P. H. Makela, J. K. Huttunen, and V. Valtonen. 1988. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet ii:983-986.
36
36. Saikku, P., M. Leinonen, L. Tenkanen, E. Linnanmaki, M. R. Ekman, V. Manninen, M. Manttari, M. H. Frick, and J. K. Huttunen. 1992. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann. Intern. Med. 116:273-278.[Abstract/Free Full Text]
37
37. Salazar, G., G. Colombo, S. Lenna, R. Antonioli, L. Beretta, A. Santaniello, and R. Scorza. 2007. HLA-B35 influences the apoptosis rate in human peripheral blood mononucleated cells and HLA-transfected cells. Hum. Immunol. 68:181-191.[CrossRef][Medline]
38
38. Santaniello, A., G. Salazar, S. Lenna, R. Antonioli, G. Colombo, L. Beretta, and R. Scorza. 2006. HLA-B35 upregulates the production of endothelin-1 in HLA-transfected cells: a possible pathogenetic role in pulmonary hypertension. Tissue Antigens 68:239-244.[CrossRef][Medline]
39
39. Sinisalo, J., K. Mattila, V. Valtonen, O. Anttonen, J. Juvonen, J. Melin, H. Vuorinen-Markkola, and M. S. Nieminen. 2002. Effect of 3 months of antimicrobial treatment with clarithromycin in acute non-Q-wave coronary syndrome. Circulation 105:1555-1560.[Abstract/Free Full Text]
40
40. Siren, M. K., H. Sareneva, M. L. Lokki, and S. Koskimies. 1996. Unique HLA antigen frequencies in the Finnish population. Tissue Antigens 48:703-707.[Medline]
41
41. Virok, D., A. Loboda, L. Kari, M. Nebozhyn, C. Chang, C. Nichols, V. Endresz, E. Gonczol, K. Berencsi, M. K. Showe, and L. C. Showe. 2003. Infection of U937 monocytic cells with Chlamydia pneumoniae induces extensive changes in host cell gene expression. J. Infect. Dis. 188:1310-1321.[CrossRef][Medline]
42
42. von Hertzen, L., H. Alakarppa, R. Koskinen, K. Liippo, H. M. Surcel, M. Leinonen, and P. Saikku. 1997. Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease. Epidemiol. Infect. 118:155-164.[CrossRef][Medline]
43
43. Wang, S. P., and J. T. Grayston. 1970. Immunologic relationship between genital TRIC lymphogranuloma venerum, and related organisms in a new microtiter indirect immunofluorescence method. Am. J. Ophthalmol. 70:367-374.[Medline]
44
44. Wiedeman, J. A., R. Kaul, L. S. Heuer, N. N. Thao, K. E. Pinerton, and W. M. Wenman. 2005. Tobacco smoke induces a persistent, but recoverable state in Chlamydia pneumoniae infection of human endothelial cells. Microb. Pathog. 39:197-204.[Medline]
45
45. Yoon, S. K., J. Y. Han, C. W. Pyo, J. M. Yang, J. W. Jang, C. W. Kim, U. I. Chang, S. H. Bae, J. Y. Choi, K. W. Chung, H. S. Sun, H. B. Choi, and T. G. Kim. 2005. Association between human leukocytes antigen alleles and chronic hepatitis C virus infection in the Korean population. Liver Int. 25:1122-1127.[CrossRef][Medline]

---

Clinical and Vaccine Immunology, January 2008, p. 55-59, Vol. 15, No. 1
1071-412X/08/$08.00+0     doi:10.1128/CVI.00163-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Palikhe, A. Articles by Sinisalo, J. Search for Related Content PubMed PubMed Citation Articles by Palikhe, A. Articles by Sinisalo, J.