RESUMO

Cystic fibrosis (CF) is the most frequent life threatening autosomal recessive disease in white subjects. The primary cause of morbidity and mortality in children with CF is chronic pulmonary infection, mainly caused by Pseudomonas aeruginosa. The purpose of this study was to assess the value of the measurement of antibodies to P. aeruginosa in diagnosing lung infection by the bacteria in CF patients. We assessed P. aeruginosa antibody titers in CF patients from Rio de Janeiro, Brazil, using cell lysate antigens as well as recombinant PcrV, a Type III Secretion System protein. Sputum (more than 70% of the specimens) or oropharyngeal swabs were obtained whenever patients were regularly followed for their pulmonary disease. Blood samples were obtained with an average interval of 6 months for a period of 2 years. The ELISA cut-offs were assigned as the positive 95% confidence interval of the mean antibody levels from non-fibrocystic controls. Our data showed that most CF patients (81%) of whom were not chronically infected by P. aeruginosa (Groups I and II), had their first serology positive for rPcrV. Cell-lysate ELISA was able to detect P. aeruginosa antibodies before positive culture in the first serum sample of 44% of the patients from Groups I and II. When serum reactivity to rPcrV and cell lysate were combined, 94% of CF patients from Groups I and II (n = 16) had the first serology positive for P. aeruginosa over a mean time of 20 months before the first isolation of P. aeruginosa. In conclusion, longitudinal P. aeruginosa serology should become part of respiratory care follow-up, in conjunction with other lung parameter functions.

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Objetivo: avaliar o diagnóstico da infecção e colonização pulmonar por Pseudomonas aeruginosa (Pa), através da detecção de anticorpos séricos específicos em pacientes fibrocísticos.Fontes pesquisadas: foi revisada a base de dados Medline, no período de 1986 a 2007, com os descritores fibrose cística e pseudomonas. Síntese dos dados: as alterações no transporte de íons nas células epiteliais levam à obstruçãocrônica das vias aéreas, com infecções secundárias. A Pa mucóide é o principal agente que aumenta a morbidade e a mortalidade nos pacientes fibrocísticos. A erradicação da bactéria é possível com antibioticoterapia precoce, queaumenta a sobrevida dos pacientes. A cultura de secreções respiratórias apresenta limitação como método diagnóstico, pela dificuldade decoleta da amostra. Parece promissora a detecção de anticorpos específicos no soro para Pa, que, em muitos casos, precede o isolamento bacterianoem cultura. O método mais utilizado é ode ELISA, com pesquisa de IgG ou IgG, IgM, e IgA. A positividade da sorologia não discrimina entre colonização e infecção pulmonar e, a condutaantibiótica não é uniforme nessa situação. Conclusões: a pesquisa sorológica de anticorpos para Pa pode ser útil no tratamento do pacientefibrocístico. Complementa a avaliação clínica, permite reavaliações não invasivas durante a evolução e possibilita a antibioticoterapia precoceem parte dos casos.

Objective: to evaluate the diagnosis of lung infection and colonization by Pseudomonas aeruginosa (Pa) through the detection of specific seric antibodies in fibrocystic patients. Data sources: the Medline database, was searched in the period 1986 to 2007, with the keywords cystic fibrosisand pseudomonas. Data synthesis: the epithelium cells disturb in ion transport cause a chronic airways obstruction, with secondary infections. Themucoid Pa is the main agent that increases morbidity and mortality in fibrocystic patients. The Objective: to evaluate the diagnosis of lung infectionand colonization by Pseudomonas aeruginosa (Pa) through the detection of specific seric antibodies in fibrocystic patients. Data sources: the Medline database, was searched in the period1986 to 2007, with the keywords cystic fibrosis and pseudomonas. Data synthesis: the epithelium cells disturb in ion transport cause a chronic airwaysobstruction, with secondary infections. The mucoid Pa is the main agent that increases morbidity and mortality in fibrocystic patients. The bacteria eradication is possible with early antibiotic therapy, which increases patients’ survival period. Respiratory secretions culture is limited as a diagnostic method, due to the difficulty incollecting samples. The detection of specific antibodies in serum for Pa, which in many cases precedesthe bacteria isolation in culture, seems to be promising. The most used method is the ELISA, with survey of IgG or IgG, IgM, and IgA. The serological positive result does not make a distinctionbetween lung colonization and infection, and the antibiotic procedure is not uniform in such situation. Conclusions: the serological antibodies survey for Pa can be useful in the treatment of fibrocystic patients. It completes the clinical evaluation, allowing non invasive reevaluations during the evolution as well as an early antibiotictherapy in some cases.

Objetivo: evaluar el diagnostico de la infección y colonización pulmonar por Pseudomonas aeruginosa (Pa) en pacientes con fibrosis cística, mediante la detección de anticuerpos sericosespecíficos. Fuente de los datos: fueron seleccionados los artículos en la base de datos Medline publicados entre 1986 y 2007, con las palabras clave fibrose cistica y pseudomonas. Síntesis delos datos: las alteraciones en el transporte de los iones de las células epiteliales llevan a la obstruccióncrónica de las vias aereas, con infecciones secundarias. La Pa mucoide es el principal agente que aumenta la morbidad y mortalidad de los pacientes fibrocisticos. La eliminación de labacteria es posible con antibióticoterapia precoz, qui determina mayor sobrevida de los pacientes.Lo cultivo de secreciones respiratorias presenta limitación como método diagnóstico, determinada por la dificultad de recolectar la muestra. Ladetección de anticuerpos específicos en el suero para Pa en muchos casos precede el islamiento bacteriano en cultura. Lo metodo más utilizadoes el de ELISA, con pesquisa de IgG, o IgG IgM y IgA. El resultado positivo non discrimina entre la ocurrencia de colonización o infección pulmonary, por lo tanto, a conducta non es uniforme en esta situación. Conclusiones: la pesquisa serologicade anticuerpos para Pa puede ser util en el tratamiento del paciente con fibrose cística. Complementa la evaluación clinica, permite reevaluaciones non invasivas, y posibilita la antibioticoterapia precoz en parte dos casos.

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IFN-gamma responses to Mycobacterium tuberculosis antigens ESAT-6 and CFP-10 have been proposed as specific markers of M. tuberculosis infection. Monokine induced by gamma interferon (MIG/CXCL9) has been shown to be expressed by IFN-gamma stimulated mononuclear cells and to attract activated T-cells through the chemokine receptor CXCR3. Since MIG is induced early in the response to IFN-gamma, measuring MIG may provide an interesting marker to assess downstream IFN-gamma induced responses, in contrast to assays that mainly focus on quantifying production of IFN-gamma per se. We, therefore, investigated MIG and IFN-gamma responses to a fusion protein of ESAT-6 and CFP-10, and compared responses to the conserved mycobacterial antigen 85B (Ag85B) and purified protein derivative (PPD) of M. tuberculosis, in 29 BCG vaccine controls and 24 TB patients. IFN-gamma secreting cells were determined by ELISPOT, and MIG production was measured by ELISA and flow cytometry. Production of MIG in response to ESAT-6/CFP-10, Ag85B and PPD correlated overall with increased numbers of IFN-gamma secreting cells (r=0.55, P<0.0001). A significant increase was noted among patients compared to controls in the secretion of IFN-gamma and MIG following stimulation with ESAT-6/CFP-10 or PPD (P<0.05). Moreover, MIG intracellular expression was higher in TB patients compared to BCG vaccines (P<0.05) in response to ESAT-6/CFP-10 or PPD. We conclude that MIG production correlates significantly with enhanced T-cell IFN-gamma production induced by M. tuberculosis-specific antigens ESAT-6/CFP-10. These results point to MIG as a potential novel biomarker that may be helpful in assessing downstream responses induced by IFN-gamma in TB.

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