RESUMEN
BACKGROUND: The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. METHODS: A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T-cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre-defined criteria. A cost analysis of diagnostic testing was performed. RESULTS: Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1-year post-transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. CONCLUSION: The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings.
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Huésped Inmunocomprometido , Receptores de Trasplantes , Humanos , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Receptores de Trasplantes/estadística & datos numéricos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anciano , Trasplante de Órganos/efectos adversos , Incidencia , Mycoplasma pneumoniae/inmunología , Mycoplasma pneumoniae/aislamiento & purificación , Bordetella pertussis/inmunología , Bordetella pertussis/aislamiento & purificación , Chlamydophila pneumoniae/inmunología , Connecticut/epidemiologíaRESUMEN
OBJECTIVE: Cerebral microbleeds (CMBs) is a subtype of cerebral small vessel disease. Their underlying pathogenesis remains unclear. The aim of this study was to investigate the association between infectious burden (IB) and CMBs. METHODS: Seven hundred and seventy-three consecutive patients who were hospitalized in the Department of Neurology in General Hospital of Western Theater Command without severe neurological symptoms were recruited and selected in this pilot cross-sectional study. CMBs were assessed using the susceptibility-weighted imaging sequence of magnetic resonance imaging. Immunoglobulin G antibodies against common pathogens, including herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus (CMV), Chlamydia pneumoniae (C. pneumoniae), Mycoplasma pneumoniae (M. pneumoniae), Epstein-Barr virus (EBV), Helicobacter pylori (HP), and Borrelia burgdorferi (B. burgdorferi), were measured by commercial ELISA assays. IB was defined as a composite serologic measure of exposure to these common pathogens. RESULTS: Patients with and without CMBs were defined as the CMBs group (n = 76) and the non-CMBs group (n = 81), respectively. IB was significantly different between the CMBs and non-CMBs groups. After adjusted for other risk factors, the increased IB was independently associated with the presence of CMBs (P = 0.031, OR = 3.00, 95% CI [1.11-8.15]). IB was significantly positively associated with the number of CMBs (Spearman ρ = 0.653, P < 0.001). The levels of serum inflammatory markers were significantly different between the CMBs and non-CMBs groups and among the categories of IB. INTERPRETATION: IB consisting of HSV-1, HSV-2, CMV, C. pneumoniae, M. pneumoniae, EBV, HP, and B. burgdorferi was associated with CMBs. All the findings suggested that pathogen infection could be involved in the pathogenesis of CMBs.
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Biomarcadores/sangre , Hemorragia Cerebral , Enfermedades de los Pequeños Vasos Cerebrales , Anciano , Borrelia burgdorferi/inmunología , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/microbiología , Hemorragia Cerebral/fisiopatología , Hemorragia Cerebral/virología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/microbiología , Enfermedades de los Pequeños Vasos Cerebrales/fisiopatología , Enfermedades de los Pequeños Vasos Cerebrales/virología , Chlamydophila pneumoniae/inmunología , Estudios Transversales , Citomegalovirus/inmunología , Femenino , Helicobacter pylori/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Inmunoglobulina G/sangre , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mycoplasma pneumoniae/inmunología , Proyectos Piloto , Factores de Riesgo , Simplexvirus/inmunologíaRESUMEN
Purpose: Mycoplasma pneumoniae (M. pneumoniae) and Chlamydophila pneumoniae (C. pneumoniae) play a significant role in children of all ages with lower respiratory tract infections (LRTIs). This study was conducted to detect M. pneumoniae and C. pneumoniae in children with community-acquired LRTIs employing serology, polymerase chain reaction (PCR) and nested PCR analysis. Material and Methods: This study included 75 children with acute LRTIs for detection of M. pneumoniae and C. pneumoniae. Blood was obtained for M. pneumoniae and C. pneumoniae antibodies and nasopharyngeal aspirates for M. pneumoniae PCR and C. pneumoniae nested PCR. Results: M. pneumoniae infection was positive in 9 (64.21%) children aged 2-6 months and in 5 (35.79%) aged 7 months-12 years, and this difference was statistically significant (P = 0.002). C. pneumoniae infection was comparable within the age group and statistically insignificant (P = 0.43). Clinical and radiological profiles of M. pneumoniae- and C. pneumoniae-positive and negative patients were numerically comparable. Serology and PCR together detected M. pneumoniae infection in 14 (18.6%) children. The sensitivity, specificity and positive and negative predictive values of serology were 77.78%, 92.42%, 58.33% and 96.83%, respectively. C. pneumoniae infection was positive in 11 (14.6%) children by serology and nested PCR with 50% sensitivity, 87.67% specificity, 10% positive predictive value and 98.46% negative predictive value. Conclusions: Our study confirms that M. pneumoniae and C. pneumoniae play a significant role in community-acquired LRTIs and a combination of serology and nested PCR is useful for its diagnosis.
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Infecciones por Chlamydophila/diagnóstico , Chlamydophila pneumoniae , Infecciones Comunitarias Adquiridas/diagnóstico , Neumonía por Mycoplasma/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Anticuerpos Antibacterianos/sangre , Niño , Preescolar , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/inmunología , Chlamydophila pneumoniae/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Masculino , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/inmunología , Mycoplasma pneumoniae/aislamiento & purificación , Neumonía Bacteriana/diagnóstico , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Pruebas SerológicasRESUMEN
Rosacea is a complex facial skin condition associated with abnormal inflammation and vascular dysfunction. Next to the known trigger factors, the role of microbiota in the development and aggravation of rosacea continues to raise interest. Demodex folliculorum mites, Helicobacter pylori, Staphylococcus epidermidis, Chlamydia pneumoniae, and the Demodex-associated bacterium, Bacillus oleronius are microbes that have been linked with rosacea. However, the results of studies which assessed their involvement in the disease have been inconsistent and inconclusive. Microbiological research in many different disciplines exploded in recent years as methods to analyze complex microbial communities at the taxonomic and phylogenetic levels became available. Here, we provide an update on the microorganisms implicated in rosacea and review the potential pathogenic role of microbes in the development of rosacea.
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Microbiota/inmunología , Infestaciones por Ácaros/complicaciones , Ácaros/microbiología , Rosácea/inmunología , Piel/microbiología , Animales , Bacillus/inmunología , Chlamydophila pneumoniae/inmunología , Helicobacter pylori/inmunología , Humanos , Infestaciones por Ácaros/inmunología , Infestaciones por Ácaros/microbiología , Infestaciones por Ácaros/parasitología , Rosácea/microbiología , Piel/inmunología , Piel/parasitología , Staphylococcus epidermidis/inmunologíaRESUMEN
BACKGROUND: Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infection. There may exist an association between C. pneumoniae, asthma, and production of immunoglobulin (Ig) E responses in vitro. Interleukin (IL-4) is required for IgE production. OBJECTIVE: We previously demonstrated that doxycycline suppresses C. pneumoniae-induced production of IgE and IL-4 responses in peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Whereas macrolides have anti-chlamydial activity, their effect on in vitro anti-inflammatory (IgE) and IL-4 responses to C. pneumoniae have not been studied. METHODS: PBMC from IgE- adult atopic subjects (N = 5) were infected +/- C. pneumoniae BAL69, +/- azithromycin (0.1, 1.0 ug/mL) for 10 days. IL-4 and IgE levels were determined in supernatants by ELISA. IL-4 and IgE were detected in supernatants of PBMC (day 10). RESULTS: When azithromycin (0.1, 1.0 ug/ml) was added, IL-4 levels decreased. At low dose, IgE levels increased and at high dose, IgE levels decreased. When PBMC were infected with C. pneumoniae, both IL-4 and IgE levels decreased. Addition of azithromycin (0.1, 1.0 ug/mL) decreased IL-4 levels and had no effect on IgE levels. CONCLUSIONS: These findings indicate that azithromycin decreases IL-4 responses but has a bimodal effect on IgE responses in PBMC from atopic patients in vitro.
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Azitromicina/farmacología , Chlamydophila pneumoniae/inmunología , Inmunoglobulina E/biosíntesis , Interleucina-4/biosíntesis , Anciano , Antibacterianos/farmacología , Asma/complicaciones , Asma/tratamiento farmacológico , Asma/inmunología , Infecciones por Chlamydophila/complicaciones , Infecciones por Chlamydophila/tratamiento farmacológico , Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/efectos de los fármacos , Chlamydophila pneumoniae/patogenicidad , Femenino , Humanos , Hipersensibilidad Inmediata/complicaciones , Hipersensibilidad Inmediata/inmunología , Hipersensibilidad Inmediata/microbiología , Inmunoglobulina E/sangre , Técnicas In Vitro , Interleucina-4/sangre , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/microbiología , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/inmunología , Adulto JovenRESUMEN
Protective immune response to chlamydial infection is largely dependent on cell-mediated immune responses with IFN-γ production. Recent studies have shown the critical role of NK cells in bridging innate and adaptive immune responses. In this study, we investigated the effect of NK cells on T cell responses during Chlamydophila pneumoniae (Cpn) lung infection. The results showed that NK cells play a protective role in Cpn infection and influence T cell immunity largely though modulating dendritic cells (DCs) function. Specifically, we found that NK depletion significantly impaired type 1 T cell responses, but enhanced FOXP3+Treg cells and IL-10-producing CD4+T cells. The alteration of T cell responses was associated with more disease severity and higher chlamydial growth in the lung. Further analysis of DC phenotype and cytokine profile found that DCs from NK cell-depleted mice expressed lower levels of co-stimulatory molecules and produced higher levels of IL-10 than those from control IgG-treated mice. More importantly, the adoptive transfer of DCs from NK cell-depleted mice induced a much lower degree of type 1 T cell responses but a higher amount of FOXP3+ Treg cells and IL-10-producing CD4+T cells in the recipient mice than DCs from IgG-treated mice. In contrast to the strong protective effect observed in recipients of DCs from IgG-treated mice, the recipients of DCs from NK cell-depleted mice failed to be protected against Cpn infection. The data suggest that NK cells play a critical role in coordinating innate and adaptive immunity in Cpn lung infection by modulating the DC function to influence T cell responses.
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Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/inmunología , Células Asesinas Naturales/inmunología , Traslado Adoptivo , Animales , Chlamydophila pneumoniae/metabolismo , Chlamydophila pneumoniae/patogenicidad , Citocinas/metabolismo , Células Dendríticas/inmunología , Inmunidad Celular/inmunología , Células Asesinas Naturales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Células T Asesinas Naturales/inmunología , Neumonía Bacteriana/inmunologíaRESUMEN
CHLAMYDOPHILA PNEUMONIAE: , a common cause of respiratory tract infections, rarely leads to serious conditions. A 13-year-old boy with serologically confirmed C. pneumoniae infection presented with pneumonia complicated by pericardial and bilateral pleural effusions. He had a large haemorrhagic pericardial effusion from which 1000 ml of fluid was aspirated over 10 days and a right haemorrhagic pleural effusion which required a chest drain and the removal of 700 ml over 5 days. The addition of clarithromycin to ceftriaxone appeared to enhance recovery. As far as we are aware, this is the first report in the English literature of massive haemorrhagic pericardial and pleural effusions in children owing to C. pneumoniae infection.
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Ceftriaxona/uso terapéutico , Neumonía por Clamidia/complicaciones , Neumonía por Clamidia/microbiología , Claritromicina/uso terapéutico , Pericarditis/microbiología , Pericarditis/patología , Adolescente , Ceftriaxona/administración & dosificación , Chlamydophila pneumoniae/inmunología , Chlamydophila pneumoniae/aislamiento & purificación , Claritromicina/administración & dosificación , Humanos , Inmunoglobulina G/química , Inmunoglobulina G/metabolismo , Inmunoglobulina M/química , Inmunoglobulina M/metabolismo , Masculino , Esputo/químicaRESUMEN
OBJECTIVES: Chlamydia pneumoniae is a difficult to diagnose respiratory pathogen. This study was performed to systematically characterize humoral immune responses to selected C. pneumoniae antigens in order to provide novel serodiagnostic perspectives for clinical and epidemiological issues. METHODS: Based on a literature search, gene library screening, and serological proteome analysis, 15 immunogenic surface-associated, virulence-associated, and hypothetical C. pneumoniae antigens were selected, recombinantly expressed, and lined on a nitrocellulose strip. Specific IgM and IgG reactivity was measured in a total of 172 PCR- and micro-immunofluorescence testing (MIF)-characterized serum samples from patients with respiratory infections. A theoretical model was conceived to approximate a putative course of C. pneumoniae antigen expression and assess the potential of early and late antigens. RESULTS: While surface antigens performed poorly, the virulence-associated TARP was a reliable antigen for IgM detection, with a sensitivity of 80.0% and a diagnostic specificity of 90.2%. The hypothetical protein YwbM proved powerful for IgG detection with MIF-correlative sensitivities of up to 94.4% and a diagnostic specificity of 95.1%. CONCLUSIONS: This study provides new insights into antibody profiles to immunogenic proteins in C. pneumoniae infection. The study findings offer antigen candidates for more reliable and standardized serological investigations of C. pneumoniae infections, including studies on seroprevalence and epidemiology.
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Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Infecciones por Chlamydia/inmunología , Chlamydophila pneumoniae/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Infecciones por Chlamydia/diagnóstico , Chlamydophila pneumoniae/genética , Femenino , Humanos , Inmunidad Humoral , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Proteínas Recombinantes/inmunología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/inmunología , Pruebas Serológicas , Adulto JovenRESUMEN
Cross-reactivity of classical chlamydial antigens compromises Chlamydia (C.) pneumoniae serology. By testing with 185 human antisera, we expanded 18 previously discovered C. pneumoniae-specific B-cell epitopes to 48 peptide antigens from 12 C. pneumoniae immunodominant proteins. For specific detection of antibodies against C. pneumoniae, we developed novel ELISAs with strongly reactive individual peptide antigens and mixtures of these peptides. By comparison to a composite reference standard (CRS) for anti-C. pneumoniae antibody status of human sera, the top-performing CpnMixF12 peptide assay showed 91% sensitivity at 95% specificity, significantly higher than 4 commercial anti-C. pneumoniae IgG ELISAs (36-12% sensitivity at 95% specificity). Human C. pneumoniae (Cpn) and C. trachomatis (Ctr) seroreactivity was 54% biased towards co-positivity in commercial Cpn and Ctr ELISAs, but unbiased in Cpn and Ctr peptide antibody assays, suggesting severe cross-reactivity of commercial ELISAs. Using hyperimmune mouse sera against each of 11 Chlamydia spp., we confirm that commercial Cpn and Ctr ELISA antigens are cross-reactive among all Chlamydia spp., but Cpn and Ctr peptide antigens react only with antisera against the cognate chlamydial species. With simultaneously high specificity and sensitivity, and convenient use for non-specialized laboratories, these ELISAs have the potential to improve serodiagnosis of C. pneumoniae infection.
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Chlamydophila pneumoniae/inmunología , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Péptidos/sangre , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/sangre , Linfocitos B/inmunología , Secuencia Conservada , Epítopos/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Ratones , Estándares de ReferenciaRESUMEN
Scrub typhus is an acute febrile illness caused by the obligate intracellular organism Orientia tsutsugamushi, endemic to South Korea. The course of scrub typhus can range from a self-limiting disease to a fatal illness. Serological cross-reactivity has been reported with other intracellular organisms, including Rickettsia species, Chlamydophila species, and Mycoplasma pneumoniae. We conducted a retrospective study to assess the current seroprevalence of M. pneumoniae IgM and Chlamydia pneumoniae IgM in scrub typhus patients in South Korea. We enrolled 150 patients with suspected rickettsial disease over the course of 2 years. Of these patients, 60 were confirmed to have scrub typhus and had paired acute and convalescent serum. Among the 60 scrub typhus patients, 40 (66.7%) had M. pneumoniae IgM and 19 (31.7%) had C. pneumoniae IgM in acute- or convalescent phase sera. The seroconversion rates of M. pneumoniae IgG and IgM were 16.7% and 33.3%, respectively. The seroconversion rates of C. pneumoniae IgG and IgM were 8.3% and 11.7%, respectively. Compared with previous study results, this may indicate a relatively high seroprevalence of M. pneumoniae IgM and C. pneumoniae IgM in scrub typhus patients, indicating possible misdiagnosis of M. pneumoniae and C. pneumoniae infections in non-endemic scrub typhus areas.
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Anticuerpos Antibacterianos/sangre , Chlamydophila pneumoniae/inmunología , Mycoplasma pneumoniae/inmunología , Orientia tsutsugamushi/inmunología , Tifus por Ácaros/diagnóstico , Anciano , Anciano de 80 o más Años , Reacciones Cruzadas , Errores Diagnósticos , Pruebas Diagnósticas de Rutina , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Estudios Retrospectivos , Tifus por Ácaros/epidemiología , Tifus por Ácaros/microbiología , Estudios SeroepidemiológicosRESUMEN
Purpose: The investigation of anti-inflammatory and immunosuppressive functions of Kynurenic acid (KYNA) is now in focus. There is also substantial evidence that TSG-6 has an anti-inflammatory activity. Therefore, in the present study, we compared the effects of newly synthetized KYNA analogs on the TNF-α production in U-937 monocytic cells in correlation with the effects on the TSG-6 expression. Methods: TNF-α production was measured by ELISA, the TSG-6 expression was determined by RTqPCR method. As cytokine inducers Staphylococcus aureus and Chlamydia pneumoniae were used. Results: KYNA and KYNA analogs attenuated TNF-α production and increased TSG-6 mRNA expression in U-937 cells stimulated by heat inactivated Staphylococcus aureus. In contrast, KYNA and some of the KYNA analogs increased the TNF-α production of C. pneumoniae infected U-937 cells; however, the newly synthetized analogs (SZR104, SZR 105, and SZR 109) exerted significant inhibitory effects on the TNF-α synthesis. The inhibitory and stimulatory effects correlated inversely with the TSG-6 expression. Conclusions: TSG-6 expression following activation with bacterial components could participate in the suppression of inflammatory cytokines, such as TNF-α, We suppose that the elevation of the TSG-6 expression by KYNA and especially by new KYNA analogs might be one of the mechanisms that are responsible for their suppressive effect on TNF-α production as a feedback mechanism. KYNA and KYNA analogs have an important role in influencing TSG-6 expression, and there is a possible benefit of targeting TSG-6 expression by kynurenines in inflammatory conditions following infections.
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Moléculas de Adhesión Celular/genética , Chlamydophila pneumoniae/inmunología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ácido Quinurénico/farmacología , Staphylococcus aureus/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/inmunología , Moléculas de Adhesión Celular/metabolismo , Ensayo de Inmunoadsorción Enzimática , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Ácido Quinurénico/análogos & derivados , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células U937 , Vacunas Atenuadas/inmunologíaRESUMEN
BACKGROUND AND AIMS: The long-term effect of immune tolerance has not been explored so far in atherosclerosis. In the present study, we assessed the effect of mucosal tolerance to a multi antigenic construct expressing three peptides from ApoB, HSP60, and outer membrane protein from Chlamydia pneumonia (AHC) for 30 weeks at every 6-week interval to understand the kinetics of immune modulation in disease progression. The safety profile of the molecule was also evaluated in mice. METHODS: Apobtm2SgyLdlrtm1Her/J mice (5-6 weeks) were orally dosed with multi antigenic construct (AHC) molecule on alternate days, followed by high-fat diet feeding to initiate atherosclerosis. RESULTS: Treated animals showed an efficient reduction in plaque growth and lipid accumulation at 6 weeks (49%, p < 0.01) and 12 weeks (42.3%, p < 0.01) which decreased to 29% (p = 0.0001) at 18 weeks and at later time points. Macrophage accumulation was significantly lower at all time points (53% at 12 weeks to 27% at 30 weeks). Regulatory T cells increased in the spleen following treatment until 12 weeks (week 0 (2.57 ± 0.18 vs. 6.36 ± 0.03, p = 0.02), week 6 (4.52 ± 0.2 vs. 8.87 ± 0.32, p = 0.02), and week 12 (8.74 ± 0.37 vs. 15.4 ± 0.27, p = 0.02)) but showed a decline later. A similar trend was observed with tolerogenic dendritic cells. We observed an increase in antibody levels to low-density lipoprotein and oxidized LDL at later stages. AHC molecule was found to be safe in acute and repeated dose toxicity studies. CONCLUSIONS: Our results suggest that immune tolerance to AHC protein by oral administration is able to provide efficient atheroprotection up to 18 weeks and moderately at later stages. Apart from immune regulatory cells, protective antibodies may also have a role in controlling atherosclerosis.
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Aterosclerosis/tratamiento farmacológico , Tolerancia Inmunológica/efectos de los fármacos , Inmunidad Mucosa/efectos de los fármacos , Factores Inmunológicos/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Animales , Antígenos Bacterianos/administración & dosificación , Antígenos Bacterianos/inmunología , Apolipoproteína B-100/administración & dosificación , Apolipoproteína B-100/genética , Apolipoproteína B-100/inmunología , Aterosclerosis/sangre , Aterosclerosis/inmunología , Aterosclerosis/patología , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/inmunología , Biomarcadores/sangre , Chaperonina 60/administración & dosificación , Chaperonina 60/inmunología , Chlamydophila pneumoniae/inmunología , Modelos Animales de Enfermedad , Femenino , Factores Inmunológicos/inmunología , Lípidos/sangre , Lípidos/inmunología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Fragmentos de Péptidos/inmunología , Placa Aterosclerótica , Receptores de LDL/genética , Receptores de LDL/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: This study aims to investigate the chlamydia pneumoniae infection (PC) in patients with coronary heart disease. METHODS: A total of 92 patients with coronary heart disease, who were treated with percutaneous coronary intervention (PCI), were selected as the case group. In addition, 50 healthy people were enrolled as the control group. The incidences of CP infection and serum Chlamydia pneumoniae IgA antibody (CP-IgA), high sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were compared in these two groups. The classification of coronary artery lesion, the incidence of perioperative cardiovascular events, and adverse prognosis events within six months after procedure were compared. RESULTS: The incidence of CP infection in the case group was higher (42.4% vs. 0%, P < 0.05). Furthermore, 17 patients were at grade I, 39 patients were at grade II, and 36 patients were at grade III. The incidences for these three kinds of patients were 17.6, 30.8, and 66.7%. The incidence of CP infection at grade III was higher than that of grade I or II (P < 0.05). Serum CP-IgA, hs-CRP and IL-6 levels increased with the severity of the coronary artery disease (P < 0.05), and the serum hs-CRP and IL-6 levels of patients with perioperative cardiovascular events were higher (P < 0.05). Moreover, the serum CP-IgA levels of the patients with adverse prognosis events were also higher (P < 0.05). CONCLUSIONS: Patients with coronary heart disease have a high CP infection rate. The degree of infection is relevant to the severity of the coronary artery lesions and postoperative prognosis of patients, suggesting that CP infection may be an important factor affecting the incidence and prognosis of coronary heart disease.
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Infecciones por Chlamydophila/epidemiología , Chlamydophila pneumoniae/patogenicidad , Enfermedad Coronaria/epidemiología , Anticuerpos Antibacterianos/sangre , Beijing/epidemiología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Infecciones por Chlamydophila/sangre , Infecciones por Chlamydophila/diagnóstico , Chlamydophila pneumoniae/inmunología , Enfermedad Coronaria/sangre , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/terapia , Femenino , Humanos , Inmunoglobulina A/sangre , Incidencia , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Recent epidemiological or immunopathological studies demonstrate the possible association between giant cell arteritis and infectious agents including Chlamydia pneumoniae. A 62-year-old Japanese man with type 1 diabetes mellitus developed biopsy-proven giant cell arteritis after acute upper respiratory infection. Serological examination indicated concurrent re-infection with C. pneumoniae. Clinical manifestations of the vasculitis subsided within a month without any immunosuppressive therapy, and no relapse was observed for the following 12 months. The natural history of this disease is unclear and spontaneous remission is rarely reported. The self-limiting nature of the infection could contribute to this phenomenon.
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Anticuerpos Antibacterianos/sangre , Chlamydophila pneumoniae/inmunología , Chlamydophila pneumoniae/patogenicidad , Arteritis de Células Gigantes/sangre , Arteritis de Células Gigantes/inmunología , Infecciones del Sistema Respiratorio/sangre , Anticuerpos Antibacterianos/inmunología , Arteritis de Células Gigantes/microbiología , Humanos , Masculino , Persona de Mediana Edad , Remisión Espontánea , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
We have shown previously that intranasal vaccination with recombinant chlamydial protease-like activity factor (rCPAF: antigen) and interleukin-12 (IL-12) as an adjuvant induces robust protection against pathological consequences of female genital tract infection with Chlamydia muridarum, a closely related species and a rodent model for the human pathogen Chlamydia trachomatis. Another related species Chlamydia pneumoniae, a human respiratory pathogen, has been associated with exacerbation of atherosclerotic pathology. CPAF is highly conserved among Chlamydia spp. leading us to hypothesize that immunization with rCPAF with IL-12 will protect against high-fat diet (HFD) and C. pneumoniae-induced acceleration of atherosclerosis. rCPAF ± IL-12 immunization induced robust splenic antigen (Ag)-specific IFN-γ and TNF-α production and significantly elevated serum total anti-CPAF Ab, IgG2c, and IgG1 antibody levels compared to mock or IL-12 alone groups. The addition of IL-12 to rCPAF significantly elevated splenic Ag-specific IFN-γ production and IgG2c/IgG1 anti-CPAF antibody ratio. Following intranasal C. pneumoniae challenge and HFD feeding, rCPAF ± IL-12-immunized mice displayed significantly enhanced splenic IFN-γ, not TNF-α, response on days 6 and 9 after challenge, and significantly reduced lung chlamydial burden on day 9 post-challenge compared to mock- or IL-12-immunized mice. Importantly, rCPAF ± IL-12-immunized mice displayed significantly reduced atherosclerotic pathology in the aortas after C. pneumoniae challenge. Serum cholesterol levels were comparable between the groups suggesting that the observed differences in pathology were due to protective immunity against the infection. Together, these results confirm and extend our previous observations that CPAF is a promising candidate antigen for a multisubunit vaccine regimen to protect against Chlamydia-induced pathologies, including atherosclerosis.
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Aterosclerosis/inmunología , Infecciones por Chlamydophila/prevención & control , Chlamydophila pneumoniae/inmunología , Endopeptidasas/administración & dosificación , Interleucina-12/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Administración Intranasal , Animales , Antígenos Bacterianos/administración & dosificación , Antígenos Bacterianos/inmunología , Aterosclerosis/etiología , Aterosclerosis/prevención & control , Infecciones por Chlamydophila/complicaciones , Endopeptidasas/genética , Endopeptidasas/inmunología , Inmunogenicidad Vacunal , Interleucina-12/inmunología , Ratones , Proteínas Recombinantes/inmunologíaRESUMEN
The host immune responses that mediate Chlamydia-induced chronic disease sequelae are incompletely understood. The role of TNF-α, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2), in Chlamydia pneumoniae (CPN)-induced atherosclerosis was studied using the high-fat diet-fed male C57BL/6J mouse model. Following intranasal CPN infection, TNF-α knockout (KO), TNFR1 KO, TNFR2 KO, and TNFR 1/2 double-knockout, displayed comparable serum anti-chlamydial antibody response, splenic antigen-specific cytokine response, and serum cholesterol profiles compared to wild type (WT) animals. However, atherosclerotic pathology in each CPN-infected KO mouse group was reduced significantly compared to WT mice, suggesting that both TNFR1 and TNFR2 promote CPN-induced atherosclerosis.
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Aterosclerosis/inmunología , Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/inmunología , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Administración Intranasal , Animales , Anticuerpos Antibacterianos/sangre , Aterosclerosis/microbiología , Aterosclerosis/patología , Infecciones por Chlamydophila/microbiología , Infecciones por Chlamydophila/patología , Colesterol/sangre , Citocinas/metabolismo , Dieta Alta en Grasa , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Persistent respiratory infections caused by Chlamydia pneumoniae have been implicated in the pathogenesis of chronic diseases (e.g. asthma). Antibiotics are used to treat C. pneumoniae respiratory infections; however, the use of antibiotics as anti-inflammatory agents in treatment of asthma remains controversial. The current study investigated whether ciprofloxacin, azithromycin, or doxycycline can suppress C. pneumoniae-induced production of immunoglobulin (Ig) E or cytokines in peripheral blood mononuclear cells (PBMC) obtained from asthmatic children. Apart from blood, nasopharyngeal swab specimens were also collected to test for the presence of C. pneumoniae and/or M. pneumoniae (qPCR). PBMC (1.5 x 106) from asthmatic pediatric patients (N = 18) were infected or mock infected for 1 h ± C. pneumoniae AR-39 at a multiplicity of infection (MOI) = 0.1, and cultured ± ciprofloxacin, azithromycin, or doxycycline (0.1 or 1.0 µg/mLmL) for either 48 h (cytokines) or 10 days (IgE). Interleukin (IL)-4, interferon (IFN)-γ and IgE levels in supernatants were measured (ELISA). When PBMC were infected with C. pneumoniae, IL-4 and IFNγ production increased (p = 0.06 and 0.03, respectively); IgE levels were low. The now-elevated levels of IL-4 didn't decrease significantly after addition of ciprofloxacin, azithromycin, or doxycycline. However, infected PBMC IFNγ formation decreased significantly when 0.1 µg/mL doxycycline was employed (p = 0.04); no dose of ciprofloxacin or azithromycin had any impact. This inhibitory outcome with doxycycline lends support to the use of tetracyclines as immune modulators and anti-inflammatory medications in treatment of C. pneumoniae-infected asthma patients.
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Antibacterianos/farmacología , Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/inmunología , Doxiciclina/farmacología , Interferón gamma/sangre , Leucocitos Mononucleares/efectos de los fármacos , Adolescente , Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Asma/inmunología , Azitromicina/farmacología , Azitromicina/uso terapéutico , Niño , Infecciones por Chlamydophila/tratamiento farmacológico , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Doxiciclina/uso terapéutico , Femenino , Humanos , Inmunoglobulina E/sangre , Interleucina-4/sangre , Masculino , Mycoplasma pneumoniae/inmunología , Adulto JovenRESUMEN
Our previous studies showed that anti-citrate synthase (anti-CS) immunoglobulin (Ig)M natural autoantibodies are present in healthy individuals without previous antigen stimulation, but no studies have investigated their presence in the pericardial fluid (PF). Therefore, we detected the natural anti-CS IgG/M autoantibody levels in plasma and PF of cardiac surgery patients and investigated their relationship with cardiovascular disease-associated bacterial pathogens. PF and blood samples of 22 coronary artery bypass graft (CABG) and 10 aortic valve replacement (AVR) patients were tested for total Ig levels, natural autoantibodies and infection-related antibodies using enzyme-linked immunosorbent assay (ELISA) and Luminex methods. The B cell subsets were measured by flow cytometry. The total Ig subclass levels were four to eight times lower in PF than in plasma, but the natural anti-CS IgM autoantibodies showed a relative increase in PF. The frequency of CD19+ B lymphocytes was significantly lower in PF than in blood (P = 0·01), with a significant relative increase of B1 cells (P = 0·005). Mycoplasma pneumoniae antibody-positive patients had significantly higher anti-CS IgM levels. In CABG patients we found a correlation between anti-CS IgG levels and M. pneumoniae, Chlamydia pneumoniae and Borrelia burgdorferi antibody titres. Our results provide the first evidence that natural autoantibodies are present in the PF, and they show a significant correlation with certain anti-bacterial antibody titres in a disease-specific manner.
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Anticuerpos Antibacterianos/sangre , Autoanticuerpos/sangre , Subgrupos de Linfocitos B/citología , Enfermedades Cardiovasculares/cirugía , Citrato (si)-Sintasa/inmunología , Líquido Pericárdico/inmunología , Anticuerpos Antibacterianos/inmunología , Válvula Aórtica/cirugía , Autoanticuerpos/inmunología , Borrelia burgdorferi/inmunología , Enfermedades Cardiovasculares/inmunología , Chlamydophila pneumoniae/inmunología , Puente de Arteria Coronaria , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , Mycoplasma pneumoniae/inmunologíaRESUMEN
Chlamydia pneumoniae is an intracellular bacterium responsible for respiratory diseases and is highly involved in cardiovascular disease development, mainly atherosclerosis. The main objective of our study was to evaluate C. pneumoniae prevalence in Moroccan patients suffering from cardiovascular diseases. A total of 115 patients with cardiovascular diseases were enrolled, and their clinical and behavioral information was recorded. Blood was sampled from all patients as well as the atheroma plaques from 36 patients undergoing surgery. Nested PCR was performed for C. pneumoniae DNA detection in both peripheral blood mononuclear cells (PBMCs) and atheroma plaques. Statistical analysis was performed using EpiInfo software. Data analysis showed cardiovascular disease dominance in men, with a sex ratio M/F of 3.4, a majority of tobacco users (52.2%), and many diabetics (44.3%). A significant difference between genders was shown for tobacco use (p<0.05). Positive cases for PBMCs and atheroma plaques were 61% and 86%, respectively, and a significant difference between PBMCs and atheroma plaque infection was identified (p=0.02). Data analysis also showed that 12% of patients presented only C. pneumoniae infection as a risk factor. Therefore, the high prevalence of C. pneumoniae suggests its involvement in atherosclerosis, and further investigation is recommended for confirmation.
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Enfermedades Cardiovasculares/epidemiología , Infecciones por Chlamydophila/epidemiología , Chlamydophila pneumoniae/genética , Anticuerpos Antibacterianos/sangre , Aterosclerosis/epidemiología , Aterosclerosis/microbiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/microbiología , Infecciones por Chlamydophila/sangre , Infecciones por Chlamydophila/diagnóstico , Chlamydophila pneumoniae/inmunología , Chlamydophila pneumoniae/aislamiento & purificación , ADN Bacteriano/genética , Femenino , Humanos , Leucocitos Mononucleares/microbiología , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de RiesgoRESUMEN
INTRODUCTION: Hajj pilgrimage is the biggest and longest mass gathering in the Muslim world. Annually, about 50% of more than 2.5 million pilgrims participating in this ritual get involved in severe devastating coughs. Most coughs continue, so the pilgrims turn back home and transmit them to family members and other people. Despite the high prevalence of coughs for many years, what causes them remains unknown. Considering the pertussis-like clinical picture of the so-called "hajj coughs", the researchers conducted a study to measure antibodies against three known common atypical bacteria, namely Bordetella Pertussis, Chlamydia Pneumonia and Mycoplasma Pneumonia. PATIENTS AND METHODS: The study was done on three out of eleven groups of pilgrims from Yazd province, central Iran. The sample was selected randomly and consisted of 202 pilgrims who completed an informed consent. Their blood samples were taken, and the plasma was separated and then stored at -70 °C. After turning back from the journey, the pilgrims had their second blood samples taken. As many as 52 pilgrims failed to come for the second sampling, and two samples were broken during transportation. The final analysis was performed on the remaining 148 pairs of samples. RESULTS: Antibodies were already elevated in many pilgrims before the journey probably due to their old age (causing more exposure to pathogens) or unplanned pertussis vaccination. After their return, antibody elevation was only mild, again probably due to the old age of the participants (i.e. due to their weaker immune systems). Some antibodies even fell down without any known reason. In this study, previous hajj journey was assumed as a prophylactic factor, due to acquisition of immunity. Coughs with a prolonged pertussis-like picture were also presumed to be more related than other types of coughs to atypical pathogens. Statistical tests showed that the history of previous journeys had no prophylactic effect. Also, no correlation was found between the clinical pictures of coughs and infection with atypical bacteria. CONCLUSION: Even though some rises and falls occurred in the antibodies titer, the variations could hardly be attributed to coughs in this study. Indeed, the variation of antibodies had no meaningful relationship with clinical factors. In this regard, further studies are needed to clarify the reason for the so-called "hajj coughs", but epidemiological studies will be difficult to do until easier and more reliable methods become available for accurate diagnosis.