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Complement defects in patients with chronic rhinosinusitis
Abstracts / Molecular Immunology 56 (2013) 240–316
P CI 5
P CI 6
The role of mannose binding lectin in infectious complications of hemato-oncologic diseases
Complement defects in patients with chronic rhinosinusitis
299
M. Dobi 1,2,∗ , Î. Szilágyi 1 , D. Csuka 1 , L. Varga 1 , Z. Prohászka 1 , G. Kovács 2 , F. Fekete 3
M.Q. Gaunsbaek 1 , B. Lange 1 , A.D. Kjeldsen 1 , V. Svane-Knudsen 1 , K. Skjødt 2 , M.L. Henriksen 2 , C. Nielsen 3 , Y. Palarasah 2 , S. Hansen 2,∗
1
Semmelweis University, III. Department of Internal Medicine, Research Laboratory, Budapest, Hungary 2 Semmelweis University, II. Department of Pediatrics, Department of Heamatology, Budapest, Hungary 3 Heim Pál Children’s Hospital, Madarász Street Building, Department of Hematology, Budapest, Hungary
1
Odense University Hospital, Dept. of Otorhinolaryngology, Odense, Denmark 2 University of Southern Denmark, Dept. of Cancer & Inflammation Research, Odense, Denmark 3 Odense University Hospital, Dept. of Clinical Immunology, Odense, Denmark
Introduction: The appropriate function of the complement system is essential for protection against infections in oncologic patients; partly because of the developing neutropenia due to the malignant disease and partly because of the chemotherapy induced immunosuppression. The key element in the activation of the complement system via the lectin pathway is the appropriate functioning of mannose-binding lectin (MBL) and mannose-binding lectin-associated serine protease 2 (MASP2) complex. One of the limiting factors of this activation may be the low serum concentration of MBL. The aim of our study was to find association between polymorphisms resulting in low MBL level and activation of the MBL–MASP2 complex, and find connection between these abnormalities and the frequency and severity of febrile neutropenic episodes in children suffering from hemato-oncological diseases. Methods: 97 children with hemato-oncological diseases (76 ALL, 10 AML, 11 NHL) were enrolled and followed from the beginning of the therapy for 8 months and several characteristics of febrile neutropenic episodes were recorded. Genotypes of 4 MBL polymorphisms (−221C/G, R52C, G54D, G57E) were determined by real-time PCR. Activation of the MBL-MASP2 complex was evaluated by ELISA from samples obtained at the time of diagnosis and during an infection. Results: The number of febrile neutropenic episodes was lower and the time until the first episode was longer in patients with normal MBL level coding genotypes, than in patients with low MBL level coding genotypes (p < 0.01). Patients with wild type genotypes have higher chance for a longer period without febrile neutropenia according to the Kaplan–Meier survival analysis (p = 0.01). A correlation between the MBL–MASP2 complex activation and the MBL genotype was found, moreover activation level decreased significantly during infections (p = 0.004) in patients with low MBL level coding genotypes. Conclusion: Our results suggest that infections after immunosuppression therapy in children suffering from hemato-oncological diseases are associated with the MBL genotype. Changes of MBL–MASP2 activation confirm the important role of the lectin pathway in infections. Our results may contribute to the estimation of risk for infections in the future, that may modify therapeutic options for individuals.
Introduction: The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. Objective: We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS), and more specifically studied whether complement defects collectively predispose individuals for CRS or affect CRS severity (Gaunsbaek et al., 2012). Methods: The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. Results: We found that the frequency of complement defects was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Conclusion: Our studies show that defects in the complement system collectively may play an immunological role related to the development of CRS. However, an association between severity of symptoms and presence of complement defects could not be demonstrated.
http://dx.doi.org/10.1016/j.molimm.2013.05.166
1
Reference Gaunsbaek, et al., 2012. Complement defects in patients with chronic rhinosinusitis. PLoS ONE 7, e47383.
http://dx.doi.org/10.1016/j.molimm.2013.05.167 P CI 8 Role of mannose binding lectin in susceptibility to tuberculosis M. Krusch 1,∗ , K. Walter 1 , T. Thye 2 , S. Niemann 1 , S. Homolka 1 , C.D. Intemann 2 , J. Köhl 3 , S. Rüsch-Gerdes 1 , R.D. Horstmann 2 , C.G. Meyer 2 , S. Ehlers 1 , C. Hölscher 1 Research Center Borstel, Borstel, Germany Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany 3 University of Lübeck, Institute for Systemic Inflammation Research, Lübeck, Germany 2
Structural variants of the Mannose Binding Lectin (MBL) resulting in functional deficiencies are known to be associated with various patterns of susceptibility to infectious diseases. In this study genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls were determined and the mycobacterial isolates of the patients were characterized at the same time. By assuming a recessive mode of inheritance, a negative association between TB and the MBL2 G57E variant (odds ratio 0.60,
P CI 5
P CI 6
The role of mannose binding lectin in infectious complications of hemato-oncologic diseases
Complement defects in patients with chronic rhinosinusitis
299
M. Dobi 1,2,∗ , Î. Szilágyi 1 , D. Csuka 1 , L. Varga 1 , Z. Prohászka 1 , G. Kovács 2 , F. Fekete 3
M.Q. Gaunsbaek 1 , B. Lange 1 , A.D. Kjeldsen 1 , V. Svane-Knudsen 1 , K. Skjødt 2 , M.L. Henriksen 2 , C. Nielsen 3 , Y. Palarasah 2 , S. Hansen 2,∗
1
Semmelweis University, III. Department of Internal Medicine, Research Laboratory, Budapest, Hungary 2 Semmelweis University, II. Department of Pediatrics, Department of Heamatology, Budapest, Hungary 3 Heim Pál Children’s Hospital, Madarász Street Building, Department of Hematology, Budapest, Hungary
1
Odense University Hospital, Dept. of Otorhinolaryngology, Odense, Denmark 2 University of Southern Denmark, Dept. of Cancer & Inflammation Research, Odense, Denmark 3 Odense University Hospital, Dept. of Clinical Immunology, Odense, Denmark
Introduction: The appropriate function of the complement system is essential for protection against infections in oncologic patients; partly because of the developing neutropenia due to the malignant disease and partly because of the chemotherapy induced immunosuppression. The key element in the activation of the complement system via the lectin pathway is the appropriate functioning of mannose-binding lectin (MBL) and mannose-binding lectin-associated serine protease 2 (MASP2) complex. One of the limiting factors of this activation may be the low serum concentration of MBL. The aim of our study was to find association between polymorphisms resulting in low MBL level and activation of the MBL–MASP2 complex, and find connection between these abnormalities and the frequency and severity of febrile neutropenic episodes in children suffering from hemato-oncological diseases. Methods: 97 children with hemato-oncological diseases (76 ALL, 10 AML, 11 NHL) were enrolled and followed from the beginning of the therapy for 8 months and several characteristics of febrile neutropenic episodes were recorded. Genotypes of 4 MBL polymorphisms (−221C/G, R52C, G54D, G57E) were determined by real-time PCR. Activation of the MBL-MASP2 complex was evaluated by ELISA from samples obtained at the time of diagnosis and during an infection. Results: The number of febrile neutropenic episodes was lower and the time until the first episode was longer in patients with normal MBL level coding genotypes, than in patients with low MBL level coding genotypes (p < 0.01). Patients with wild type genotypes have higher chance for a longer period without febrile neutropenia according to the Kaplan–Meier survival analysis (p = 0.01). A correlation between the MBL–MASP2 complex activation and the MBL genotype was found, moreover activation level decreased significantly during infections (p = 0.004) in patients with low MBL level coding genotypes. Conclusion: Our results suggest that infections after immunosuppression therapy in children suffering from hemato-oncological diseases are associated with the MBL genotype. Changes of MBL–MASP2 activation confirm the important role of the lectin pathway in infections. Our results may contribute to the estimation of risk for infections in the future, that may modify therapeutic options for individuals.
Introduction: The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. Objective: We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS), and more specifically studied whether complement defects collectively predispose individuals for CRS or affect CRS severity (Gaunsbaek et al., 2012). Methods: The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. Results: We found that the frequency of complement defects was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Conclusion: Our studies show that defects in the complement system collectively may play an immunological role related to the development of CRS. However, an association between severity of symptoms and presence of complement defects could not be demonstrated.
http://dx.doi.org/10.1016/j.molimm.2013.05.166
1
Reference Gaunsbaek, et al., 2012. Complement defects in patients with chronic rhinosinusitis. PLoS ONE 7, e47383.
http://dx.doi.org/10.1016/j.molimm.2013.05.167 P CI 8 Role of mannose binding lectin in susceptibility to tuberculosis M. Krusch 1,∗ , K. Walter 1 , T. Thye 2 , S. Niemann 1 , S. Homolka 1 , C.D. Intemann 2 , J. Köhl 3 , S. Rüsch-Gerdes 1 , R.D. Horstmann 2 , C.G. Meyer 2 , S. Ehlers 1 , C. Hölscher 1 Research Center Borstel, Borstel, Germany Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany 3 University of Lübeck, Institute for Systemic Inflammation Research, Lübeck, Germany 2
Structural variants of the Mannose Binding Lectin (MBL) resulting in functional deficiencies are known to be associated with various patterns of susceptibility to infectious diseases. In this study genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls were determined and the mycobacterial isolates of the patients were characterized at the same time. By assuming a recessive mode of inheritance, a negative association between TB and the MBL2 G57E variant (odds ratio 0.60,