[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

Natural cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) is not impaired in patients suffering from chronic hepatitis C.

BACKGROUND/AIMS: Recent observations suggest that natural killer (NK) cell activity might be impaired in chronic hepatitis C. However, to date antibody-dependent cellular cytotoxicity (ADCC) has not been studied in chronic hepatitis C in detail. METHODS: Therefore, we investigated spontaneous and cytokine-induced (interleukin-2 and interferon-gamma) natural cytotoxicity and ADCC in 29 patients suffering from chronic hepatitis C and 19 healthy controls. Cytotoxicity was determined with a flow-cytometric assay, which can also assess monocyte cytotoxicity. As target cells we used the colorectal tumor cell line HT29 and the lymphoma cell line Raji. RESULTS: We found no significant differences with respect to spontaneous cytotoxicity (HCV versus healthy controls (32 vs. 46%) and 17-1A specific ADCC (59 vs. 48%), even if isolated monocytes or NK cells were studied. Preincubation and stimulation of effector cells with cytokines increased both natural cytotoxicity and ADCC by 20-30%. However, natural cytotoxicity and ADCC after stimulation did not differ between the two groups. CONCLUSIONS: Our data obtained with a long-term cytotoxicity assay do not reveal impaired cytolytic capacity of the innate immune system in chronic hepatitis C, even when isolated monocytes and NK cells were studied as effector cells.

Transient loss of T-cell reactivity in a patient with hepatitis C virus reinfection.

BACKGROUND/AIMS: Self-limited acute hepatitis C virus (HCV) infection with spontaneous recovery is only rarely observed in clinical practice. All existing studies correlate strong cellular immune responses to the recovery from HCV infection. CASE REPORT: Here, we present a 49-year-old haemophiliac, who had successfully recovered from an acute hepatitis, which was classified retrospectively as HCV infection based on his antibody profiles. This patient was reinfected with HCV 18 years later from an exogenous source, and successfully recovered from this reinfection within 2 months. After his first hepatitis the patient displayed strong cellular responses against recombinant HCV proteins. During reinfection, T-cell proliferation was markedly reduced, while HCV antibody titres increased. However, E2 antibodies were consistently not detectable. T-cell proliferation returned to the pre-reinfection level only several months after loss of viraemia. DISCUSSION: Our observations resulted in the unexpected finding that our patient cleared HCV reinfection despite an apparent loss of his pre-existing T-cell reactivity in the peripheral blood.