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Clinical Status, Serum Immunoglobulin G Subclasses and Sputum Il-10 and Mpo Levels in Cf Patients
S102 Abstracts
Clinical Status, Serum Immunoglobulin G Subclasses and Sputum Il-10 and Mpo Levels in Cf Patients A. Korzeniewska, J. Jerzynska, I. Stelmach; Department of Pediatrics and Allergy, Medical University of Lodz, M Curie Hospital, Zgierz, POLAND. RATIONALE: This study was undertaken to define a correlation between clinical status, serum immunoglobuline G (IgG) subclasses and sputum IL-10 and MPO levels in patients with CF. METHODS: We examined 17 clinical stable CF patients aged 12-30. All patients were chronic infected with Pseudomonas aeruginosa. Shwachman-Kulczycki Score (SKS) was measured. Total IgG, IgG1, IgG2, IgG3, IgG4 (mg/dl) in serum and sputum IL-10 (pg/dl) and MPO (ng/dl) levels were determined. RESULTS: Mean SKS was 76±13. Mean total IgG levels were 1510±556.9, IgG1 9.552±2.5l, IgG2 4.8±2.04, IgG3 1.058±0.6 and IgG4 1.787±0.725. Mean sputum IL-10 levels were 10.78±0.76 and MPO levels 5.01±0.53. We found significant correlation between elevated total serum IgG levels and decreased SKS (p=0.002). High levels of IgG2 were significantly correlated with decreased SKS (p=0.001). Significant correlation between IgG2 and sputum MPO (p=0.002) levels was observed; and there was significant inverse correlation between IgG2 levels and sputum IL-10 (p=0.001) levels. There was significant correlation between elevated levels of IgG4 and increased SKS (p=0.002) and IL-10 levels (p=0.003). Significant inverse correlation between IgG4 levels and sputum (p=0.001) MPO levels were observed. We found significant correlation between better SKS and IL-10 levels (p=0.002) and significant inverse correlation between SKS and sputum MPO levels (p=0.002). CONCLUSIONS: IgG2 levels showed to be a good value in predicting the severity of disease and could be a useful marker of inflammatory process in CF patients chronic infected with Pseudomonas aeruginosa. Elevated levels of IgG4 may antagonise IgG2 helping to preserve relatively good clinical status.
397
SUNDAY
Evaluation of NK T Cells in Patients with Schistosomiasis and Asthma R. A. Campos, M. S. Teles, M. J. Martins, O. F. Jesus, B. B. Andrade, A. A. Cruz, M. Araújo, E. M. Carvalho; Internal Medicine, Universidade Federal da Bahia, Salvador-BA, BRAZIL. RATIONALE: S. mansoni modulates the immune response in asthma. V24V11 NK T cells release Th1 and Th2 cytokines but there is a positive correlation between CD4 expression on NKT cells and ability to produce Th2 cytokines. NKT cell deficient mice infected with S. mansoni present reduced hepatic pathology. This study evaluated the profile of NK T cells in asthmatic patients with schistosomiasis. METHODS: We evaluated 4 groups: 1) controls; 2) asthma; 3) schistosomiasis; 4) asthma + schistosomiasis. A questionnaire for asthma was done and FACS analysis of the PBMC for NKT cells and intracellular cytokines using PE and FITC anti-V24, FITC anti-V11, Cy anti-CD4, Cy anti-CD3, PE anti-IL-4 and PE anti-IFN-. NK T cells were defined by the double expression of V24 and V11. RESULTS: We evaluated 87 subjects: 25 from group 1, 39 from group 2, 12 from group 3 and 11 from group 4. There was a reduction on NKT cells in asthma (group 1: 0.45%±0.41 and group 2: 0.14%±0.21; p=0.03) but CD4+NKT cells were higher (group 1: 35%±4.1; group 2: 57%±5.6). There was no reduction of NKT cells in schistosomiasis and in the asthmatic individuals with schistosomiasis. The NKT cell intracellular production of IL-4 was similar between groups 3 and 4. Subjects with schistosomiasis and asthma showed a non significant lower INF- production. CONCLUSIONS: In asthma, CD4+ V24V11 NKT may be preferentially producing Th2 cytokines and this may be modulated in schistosomiasis patients likely by stimulating CD4 - V24V11 NKT to produce Th1 cytokines. Funding: FAPESB
398
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
Successful Treatment Using Interleukin-2 (IL-2) in a Patient with Idiopathic CD4+ Lymphopenia (ICL) and Mycobacterium avium (M.avium) B. Mandal1, V. Bhushan2, D. Khan1; 1Allergy and Immunology, UT Southwestern, Dallas, TX, 2Hematology/Oncology, UT Southwestern, Dallas, TX. RATIONALE: ICL is a rare immune defect characterized by: CD4+ T cells count <300 cells/mm3 on more than one occasion, lack of HIV infection or other immune deficiency, and presence of opportunistic infections. Isolated case reports suggest that IL-2 is efficacious in ICL. We report a case of a patient with M.avium due to ICL who was successfully treated with IL-2. METHODS: This patient is a 39 y/o WM who presented with 2 years of chronic cough and dyspnea. A sputum culture revealed M.avium. His CD4+ T cells were decreased at 182 cells/l. Workup for other etiologies of CD4+ lymphopenia was negative including: HIV-1,2 , HTLV-1,2, chest CT and bone marrow biopsy. He was diagnosed with ICL and started on pegylated subcutaneous IL-2 at 500,000 units weekly. He was given incrementally higher doses until he reached a maintenance dosage 3 months later of 11 MU weekly. RESULTS: After 3 months of therapy, CD4+ T cells increased to 453 cells/l. Nine months after initiation of IL-2, his CD4+ T cell counts have been >450 cells/l. Sputum cultures became negative for M.avium, and he has tolerated the IL-2 with no side effects. CONCLUSIONS: IL-2 therapy appears to be a relatively safe and effective treatment for patients with ICL and should be considered for select patients to prevent the high morbidity associated with this syndrome. Funding: UT Southwestern
399
Characterization of the Suppressive Properties of Human CD4+CD25+ T Cells in Atopic and Non-Atopic Individuals A. M. L. Fonseca, C. Torres, O. M. M. Lourenco, L. M. P. Taborda-Barata; Department of Medical Sciences, Health Sciences Medical Center, University of Beira interior, Covilhã, PORTUGAL. RATIONALE: The aim of the present study was to analyze whether “regulatory” CD4+CD25+ T cells are present and function normally in atopic individuals, namely in terms of the suppression of allergen-specific proliferation and cytokine production of CD4+CD25 T cells. METHODS: Peripheral blood was obtained from 12 atopic subjects and 12 non-atopic controls and CD4+CD25+ and CD4+CD25 cells were isolated using magnetic beads. CD4+CD25+ and CD4+CD25 T cells were mixed at different ratios (2: 1, 4: 1 and 8: 1) and stimulated with Der p or PHA in 6-day co-cultures together with autologous monocytes as antigen-presenting cells. Proliferation and cytokine production was analysed using thymidine incorporation and cytometric bead array, respectively. RESULTS: Our results show that the percentage of CD4+CD25+ T cells was not significantly different between groups. CD4+CD25+ cells suppressed proliferation by their Der p-stimulated CD4+CD25 T cells in all studied samples. Moreover, the amount of IFN-, IL-2, IL-4, IL-5, Il-10, TNF- produced by the co-cultures was comparable in both groups studied. CONCLUSIONS: These preliminary data indicate that “regulatory” CD4+CD25+ T cells are equally present and functional in both atopic and non-atopic individuals. Funding: Fundacao para a Ciencia e Tecnologia
400
Clinical Status, Serum Immunoglobulin G Subclasses and Sputum Il-10 and Mpo Levels in Cf Patients A. Korzeniewska, J. Jerzynska, I. Stelmach; Department of Pediatrics and Allergy, Medical University of Lodz, M Curie Hospital, Zgierz, POLAND. RATIONALE: This study was undertaken to define a correlation between clinical status, serum immunoglobuline G (IgG) subclasses and sputum IL-10 and MPO levels in patients with CF. METHODS: We examined 17 clinical stable CF patients aged 12-30. All patients were chronic infected with Pseudomonas aeruginosa. Shwachman-Kulczycki Score (SKS) was measured. Total IgG, IgG1, IgG2, IgG3, IgG4 (mg/dl) in serum and sputum IL-10 (pg/dl) and MPO (ng/dl) levels were determined. RESULTS: Mean SKS was 76±13. Mean total IgG levels were 1510±556.9, IgG1 9.552±2.5l, IgG2 4.8±2.04, IgG3 1.058±0.6 and IgG4 1.787±0.725. Mean sputum IL-10 levels were 10.78±0.76 and MPO levels 5.01±0.53. We found significant correlation between elevated total serum IgG levels and decreased SKS (p=0.002). High levels of IgG2 were significantly correlated with decreased SKS (p=0.001). Significant correlation between IgG2 and sputum MPO (p=0.002) levels was observed; and there was significant inverse correlation between IgG2 levels and sputum IL-10 (p=0.001) levels. There was significant correlation between elevated levels of IgG4 and increased SKS (p=0.002) and IL-10 levels (p=0.003). Significant inverse correlation between IgG4 levels and sputum (p=0.001) MPO levels were observed. We found significant correlation between better SKS and IL-10 levels (p=0.002) and significant inverse correlation between SKS and sputum MPO levels (p=0.002). CONCLUSIONS: IgG2 levels showed to be a good value in predicting the severity of disease and could be a useful marker of inflammatory process in CF patients chronic infected with Pseudomonas aeruginosa. Elevated levels of IgG4 may antagonise IgG2 helping to preserve relatively good clinical status.
397
SUNDAY
Evaluation of NK T Cells in Patients with Schistosomiasis and Asthma R. A. Campos, M. S. Teles, M. J. Martins, O. F. Jesus, B. B. Andrade, A. A. Cruz, M. Araújo, E. M. Carvalho; Internal Medicine, Universidade Federal da Bahia, Salvador-BA, BRAZIL. RATIONALE: S. mansoni modulates the immune response in asthma. V24V11 NK T cells release Th1 and Th2 cytokines but there is a positive correlation between CD4 expression on NKT cells and ability to produce Th2 cytokines. NKT cell deficient mice infected with S. mansoni present reduced hepatic pathology. This study evaluated the profile of NK T cells in asthmatic patients with schistosomiasis. METHODS: We evaluated 4 groups: 1) controls; 2) asthma; 3) schistosomiasis; 4) asthma + schistosomiasis. A questionnaire for asthma was done and FACS analysis of the PBMC for NKT cells and intracellular cytokines using PE and FITC anti-V24, FITC anti-V11, Cy anti-CD4, Cy anti-CD3, PE anti-IL-4 and PE anti-IFN-. NK T cells were defined by the double expression of V24 and V11. RESULTS: We evaluated 87 subjects: 25 from group 1, 39 from group 2, 12 from group 3 and 11 from group 4. There was a reduction on NKT cells in asthma (group 1: 0.45%±0.41 and group 2: 0.14%±0.21; p=0.03) but CD4+NKT cells were higher (group 1: 35%±4.1; group 2: 57%±5.6). There was no reduction of NKT cells in schistosomiasis and in the asthmatic individuals with schistosomiasis. The NKT cell intracellular production of IL-4 was similar between groups 3 and 4. Subjects with schistosomiasis and asthma showed a non significant lower INF- production. CONCLUSIONS: In asthma, CD4+ V24V11 NKT may be preferentially producing Th2 cytokines and this may be modulated in schistosomiasis patients likely by stimulating CD4 - V24V11 NKT to produce Th1 cytokines. Funding: FAPESB
398
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
Successful Treatment Using Interleukin-2 (IL-2) in a Patient with Idiopathic CD4+ Lymphopenia (ICL) and Mycobacterium avium (M.avium) B. Mandal1, V. Bhushan2, D. Khan1; 1Allergy and Immunology, UT Southwestern, Dallas, TX, 2Hematology/Oncology, UT Southwestern, Dallas, TX. RATIONALE: ICL is a rare immune defect characterized by: CD4+ T cells count <300 cells/mm3 on more than one occasion, lack of HIV infection or other immune deficiency, and presence of opportunistic infections. Isolated case reports suggest that IL-2 is efficacious in ICL. We report a case of a patient with M.avium due to ICL who was successfully treated with IL-2. METHODS: This patient is a 39 y/o WM who presented with 2 years of chronic cough and dyspnea. A sputum culture revealed M.avium. His CD4+ T cells were decreased at 182 cells/l. Workup for other etiologies of CD4+ lymphopenia was negative including: HIV-1,2 , HTLV-1,2, chest CT and bone marrow biopsy. He was diagnosed with ICL and started on pegylated subcutaneous IL-2 at 500,000 units weekly. He was given incrementally higher doses until he reached a maintenance dosage 3 months later of 11 MU weekly. RESULTS: After 3 months of therapy, CD4+ T cells increased to 453 cells/l. Nine months after initiation of IL-2, his CD4+ T cell counts have been >450 cells/l. Sputum cultures became negative for M.avium, and he has tolerated the IL-2 with no side effects. CONCLUSIONS: IL-2 therapy appears to be a relatively safe and effective treatment for patients with ICL and should be considered for select patients to prevent the high morbidity associated with this syndrome. Funding: UT Southwestern
399
Characterization of the Suppressive Properties of Human CD4+CD25+ T Cells in Atopic and Non-Atopic Individuals A. M. L. Fonseca, C. Torres, O. M. M. Lourenco, L. M. P. Taborda-Barata; Department of Medical Sciences, Health Sciences Medical Center, University of Beira interior, Covilhã, PORTUGAL. RATIONALE: The aim of the present study was to analyze whether “regulatory” CD4+CD25+ T cells are present and function normally in atopic individuals, namely in terms of the suppression of allergen-specific proliferation and cytokine production of CD4+CD25 T cells. METHODS: Peripheral blood was obtained from 12 atopic subjects and 12 non-atopic controls and CD4+CD25+ and CD4+CD25 cells were isolated using magnetic beads. CD4+CD25+ and CD4+CD25 T cells were mixed at different ratios (2: 1, 4: 1 and 8: 1) and stimulated with Der p or PHA in 6-day co-cultures together with autologous monocytes as antigen-presenting cells. Proliferation and cytokine production was analysed using thymidine incorporation and cytometric bead array, respectively. RESULTS: Our results show that the percentage of CD4+CD25+ T cells was not significantly different between groups. CD4+CD25+ cells suppressed proliferation by their Der p-stimulated CD4+CD25 T cells in all studied samples. Moreover, the amount of IFN-, IL-2, IL-4, IL-5, Il-10, TNF- produced by the co-cultures was comparable in both groups studied. CONCLUSIONS: These preliminary data indicate that “regulatory” CD4+CD25+ T cells are equally present and functional in both atopic and non-atopic individuals. Funding: Fundacao para a Ciencia e Tecnologia
400