Eintrag weiter verarbeiten
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study
Gespeichert in:
| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , |
| In: | Blood, 116, 2010, 21, S. 4704-4704 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
|
| Schlagwörter: |
| author_facet |
Skert, Cristina Garrafa, Emirena Fogli, Manuela Fiorentini, Simona Ricotta, Doris Caimi, Luigi Filì, Carla Peli, Annalisa Bergonzi, Cesare Malagola, Michele Giovanni, Martinelli Iacobucci, Ilaria Turra, Alessandro Arpinati, Mario Cattina, Federica Caruso, Arnaldo Russo, Domenico Skert, Cristina Garrafa, Emirena Fogli, Manuela Fiorentini, Simona Ricotta, Doris Caimi, Luigi Filì, Carla Peli, Annalisa Bergonzi, Cesare Malagola, Michele Giovanni, Martinelli Iacobucci, Ilaria Turra, Alessandro Arpinati, Mario Cattina, Federica Caruso, Arnaldo Russo, Domenico |
|---|---|
| author |
Skert, Cristina Garrafa, Emirena Fogli, Manuela Fiorentini, Simona Ricotta, Doris Caimi, Luigi Filì, Carla Peli, Annalisa Bergonzi, Cesare Malagola, Michele Giovanni, Martinelli Iacobucci, Ilaria Turra, Alessandro Arpinati, Mario Cattina, Federica Caruso, Arnaldo Russo, Domenico |
| spellingShingle |
Skert, Cristina Garrafa, Emirena Fogli, Manuela Fiorentini, Simona Ricotta, Doris Caimi, Luigi Filì, Carla Peli, Annalisa Bergonzi, Cesare Malagola, Michele Giovanni, Martinelli Iacobucci, Ilaria Turra, Alessandro Arpinati, Mario Cattina, Federica Caruso, Arnaldo Russo, Domenico Blood Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study Cell Biology Hematology Immunology Biochemistry |
| author_sort |
skert, cristina |
| spelling |
Skert, Cristina Garrafa, Emirena Fogli, Manuela Fiorentini, Simona Ricotta, Doris Caimi, Luigi Filì, Carla Peli, Annalisa Bergonzi, Cesare Malagola, Michele Giovanni, Martinelli Iacobucci, Ilaria Turra, Alessandro Arpinati, Mario Cattina, Federica Caruso, Arnaldo Russo, Domenico 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v116.21.4704.4704 <jats:title>Abstract</jats:title> <jats:p>Abstract 4704</jats:p> <jats:sec> <jats:title>Background and aim of the study.</jats:title> <jats:p>Emerging trends emphasize the importance of both innate and adaptive immune system in the response against infections, in the pathogenesis of autoimmune diseases and graft-versus-host disease (GVHD). In the cross-talk between innate and adaptive immune system, pattern recognition receptors such as Toll-like receptors (TLRs) play a key role. TLRs recognize common protein, carbohydrate or DNA/RNA pattern motifs leading to signaling for cytokine production and T cell and dendritic cell maturation. These receptors may act as tuner of inflammatory and immunologic reactions. Very little is known about the expression and the function of TLRs in vivo in patients who underwent to allogeneic stem cell transplantation (SCT). The aim of this study was to evaluate the expression and the function of TLRs on lymphocytes and monocytes in relation to infection (CMV and HHV-6, especially) and the onset of GVHD.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and methods.</jats:title> <jats:p>The expression of TLRs on T cells and monocytes was analyzed by flow cytometry at day +30, +90, +180 after SCT and at the onset of GVHD. The expression of receptors for lipid-based pathogen-associated molecular patterns (PAMPs: TLR 1,2,4 and 6 surface receptors), receptors for nucleic acid based PAMPs (TLR 3,7,8 and 9 located in cytoplasmic compartments), TLR5 and, TLR10 (surface receptors) was evaluated as mean fluorescence intensity (MFI). Ex vivo induction of cytokines (TNFalpha, MCP1, IFNgamma, IL-10) by TLR ligands was analyzed in the cell supernatant by ELISA. Since the beginning of the study, we have analyzed data of 12 healthy donors and 14 patients. Median age was 46 years (range, 25–64) and 7 patients were male.</jats:p> </jats:sec> <jats:sec> <jats:title>Results.</jats:title> <jats:p>Acute GVHD developed in 7 patients. Patients without acute GVHD after SCT and healthy donors showed different MFI of TLR3 on T cells (5,8±1,4 vs 4,2±1,05 p=0,02), of TLR4 on monocytes (26,1±1,01 vs 15,8±4,9 p=0,004), and of TLR6 on T-lymphocytes (7,3±3,2 vs 4,6±1,1 p=0,02) and monocytes (27±12,1 vs 14,9±4,6 p=0,01). TLR3 expression was significantly decreased on T-lymphocytes and monocytes in patients with acute GVHD in comparison to those without GVHD (4,06±0,8 vs 5,8±1,4 p=0,02; 9,3±7,2 vs 38,02±30 p=0,04). The levels of TLR5 on T cells and monocytes were higher in patients with acute GVHD compared to healthy donors (8,4±2,1 vs 6,4±1,6 p=0,04; 54,2±20,2 vs 33,2±16,5 p=0,04). An increased induction of IFNgamma upon TLR1 ligand activation was observed in patients without GVHD in comparison to healthy donors and patients with GVHD (p=0,04). TLR6 ligand induced significantly the production of IFN gamma in patients with GVHD in comparison to controls and the other patients (p=0,03). Patients without GVHD showed a trend toward a decreased induction of MCP1 upon TLR4 ligand activation (p=0,07). The rate of infections (especially CMV reactivation), clinical and transplant characteristic were not significantly different between patients with and without GVHD.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In our study, a different expression profile of TLRs was found in healthy donors, in patients after SCT without acute GVHD and in those with GVHD. These results suggest that the innate immune response via TLRs activation could be involved in the development of GVHD. The assessment of a larger number of patients would be useful to understand the complex interplay between pathogens, self or non-self DNA and RNA and the immune system after SCT.</jats:p> </jats:sec> <jats:sec> <jats:title>Disclosures:</jats:title> <jats:p>Off Label Use: In Italy the use of azacitidine for Low-risk Myelodysplastic patients is off label. The use of azacitidine in our study is part of a Phase II clinical trial.</jats:p> </jats:sec> Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study Blood |
| doi_str_mv |
10.1182/blood.v116.21.4704.4704 |
| facet_avail |
Online Free |
| finc_class_facet |
Biologie Medizin Chemie und Pharmazie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52MTE2LjIxLjQ3MDQuNDcwNA |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52MTE2LjIxLjQ3MDQuNDcwNA |
| institution |
DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 |
| imprint |
American Society of Hematology, 2010 |
| imprint_str_mv |
American Society of Hematology, 2010 |
| issn |
0006-4971 1528-0020 |
| issn_str_mv |
0006-4971 1528-0020 |
| language |
English |
| mega_collection |
American Society of Hematology (CrossRef) |
| match_str |
skert2010expressionoftolllikereceptorsonperipheralbloodcellsafterallogeneicstemcelltransplantationongoingresultsofaprospectivestudy |
| publishDateSort |
2010 |
| publisher |
American Society of Hematology |
| recordtype |
ai |
| record_format |
ai |
| series |
Blood |
| source_id |
49 |
| title |
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_unstemmed |
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_full |
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_fullStr |
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_full_unstemmed |
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_short |
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_sort |
expression of toll-like receptors on peripheral blood cells after allogeneic stem cell transplantation: ongoing results of a prospective study |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood.v116.21.4704.4704 |
| publishDate |
2010 |
| physical |
4704-4704 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Abstract 4704</jats:p>
<jats:sec>
<jats:title>Background and aim of the study.</jats:title>
<jats:p>Emerging trends emphasize the importance of both innate and adaptive immune system in the response against infections, in the pathogenesis of autoimmune diseases and graft-versus-host disease (GVHD). In the cross-talk between innate and adaptive immune system, pattern recognition receptors such as Toll-like receptors (TLRs) play a key role. TLRs recognize common protein, carbohydrate or DNA/RNA pattern motifs leading to signaling for cytokine production and T cell and dendritic cell maturation. These receptors may act as tuner of inflammatory and immunologic reactions. Very little is known about the expression and the function of TLRs in vivo in patients who underwent to allogeneic stem cell transplantation (SCT). The aim of this study was to evaluate the expression and the function of TLRs on lymphocytes and monocytes in relation to infection (CMV and HHV-6, especially) and the onset of GVHD.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Patients and methods.</jats:title>
<jats:p>The expression of TLRs on T cells and monocytes was analyzed by flow cytometry at day +30, +90, +180 after SCT and at the onset of GVHD. The expression of receptors for lipid-based pathogen-associated molecular patterns (PAMPs: TLR 1,2,4 and 6 surface receptors), receptors for nucleic acid based PAMPs (TLR 3,7,8 and 9 located in cytoplasmic compartments), TLR5 and, TLR10 (surface receptors) was evaluated as mean fluorescence intensity (MFI). Ex vivo induction of cytokines (TNFalpha, MCP1, IFNgamma, IL-10) by TLR ligands was analyzed in the cell supernatant by ELISA. Since the beginning of the study, we have analyzed data of 12 healthy donors and 14 patients. Median age was 46 years (range, 25–64) and 7 patients were male.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results.</jats:title>
<jats:p>Acute GVHD developed in 7 patients. Patients without acute GVHD after SCT and healthy donors showed different MFI of TLR3 on T cells (5,8±1,4 vs 4,2±1,05 p=0,02), of TLR4 on monocytes (26,1±1,01 vs 15,8±4,9 p=0,004), and of TLR6 on T-lymphocytes (7,3±3,2 vs 4,6±1,1 p=0,02) and monocytes (27±12,1 vs 14,9±4,6 p=0,01). TLR3 expression was significantly decreased on T-lymphocytes and monocytes in patients with acute GVHD in comparison to those without GVHD (4,06±0,8 vs 5,8±1,4 p=0,02; 9,3±7,2 vs 38,02±30 p=0,04). The levels of TLR5 on T cells and monocytes were higher in patients with acute GVHD compared to healthy donors (8,4±2,1 vs 6,4±1,6 p=0,04; 54,2±20,2 vs 33,2±16,5 p=0,04). An increased induction of IFNgamma upon TLR1 ligand activation was observed in patients without GVHD in comparison to healthy donors and patients with GVHD (p=0,04). TLR6 ligand induced significantly the production of IFN gamma in patients with GVHD in comparison to controls and the other patients (p=0,03). Patients without GVHD showed a trend toward a decreased induction of MCP1 upon TLR4 ligand activation (p=0,07). The rate of infections (especially CMV reactivation), clinical and transplant characteristic were not significantly different between patients with and without GVHD.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>In our study, a different expression profile of TLRs was found in healthy donors, in patients after SCT without acute GVHD and in those with GVHD. These results suggest that the innate immune response via TLRs activation could be involved in the development of GVHD. The assessment of a larger number of patients would be useful to understand the complex interplay between pathogens, self or non-self DNA and RNA and the immune system after SCT.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Disclosures:</jats:title>
<jats:p>Off Label Use: In Italy the use of azacitidine for Low-risk Myelodysplastic patients is off label. The use of azacitidine in our study is part of a Phase II clinical trial.</jats:p>
</jats:sec> |
| container_issue |
21 |
| container_start_page |
4704 |
| container_title |
Blood |
| container_volume |
116 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792320726670245903 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T10:50:27.065Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Expression+of+Toll-Like+Receptors+on+Peripheral+Blood+Cells+After+Allogeneic+Stem+Cell+Transplantation%3A+Ongoing+Results+of+a+Prospective+Study&rft.date=2010-11-19&genre=article&issn=1528-0020&volume=116&issue=21&spage=4704&epage=4704&pages=4704-4704&jtitle=Blood&atitle=Expression+of+Toll-Like+Receptors+on+Peripheral+Blood+Cells+After+Allogeneic+Stem+Cell+Transplantation%3A+Ongoing+Results+of+a+Prospective+Study&aulast=Russo&aufirst=Domenico&rft_id=info%3Adoi%2F10.1182%2Fblood.v116.21.4704.4704&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792320726670245903 |
| author | Skert, Cristina, Garrafa, Emirena, Fogli, Manuela, Fiorentini, Simona, Ricotta, Doris, Caimi, Luigi, Filì, Carla, Peli, Annalisa, Bergonzi, Cesare, Malagola, Michele, Giovanni, Martinelli, Iacobucci, Ilaria, Turra, Alessandro, Arpinati, Mario, Cattina, Federica, Caruso, Arnaldo, Russo, Domenico |
| author_facet | Skert, Cristina, Garrafa, Emirena, Fogli, Manuela, Fiorentini, Simona, Ricotta, Doris, Caimi, Luigi, Filì, Carla, Peli, Annalisa, Bergonzi, Cesare, Malagola, Michele, Giovanni, Martinelli, Iacobucci, Ilaria, Turra, Alessandro, Arpinati, Mario, Cattina, Federica, Caruso, Arnaldo, Russo, Domenico, Skert, Cristina, Garrafa, Emirena, Fogli, Manuela, Fiorentini, Simona, Ricotta, Doris, Caimi, Luigi, Filì, Carla, Peli, Annalisa, Bergonzi, Cesare, Malagola, Michele, Giovanni, Martinelli, Iacobucci, Ilaria, Turra, Alessandro, Arpinati, Mario, Cattina, Federica, Caruso, Arnaldo, Russo, Domenico |
| author_sort | skert, cristina |
| container_issue | 21 |
| container_start_page | 4704 |
| container_title | Blood |
| container_volume | 116 |
| description | <jats:title>Abstract</jats:title> <jats:p>Abstract 4704</jats:p> <jats:sec> <jats:title>Background and aim of the study.</jats:title> <jats:p>Emerging trends emphasize the importance of both innate and adaptive immune system in the response against infections, in the pathogenesis of autoimmune diseases and graft-versus-host disease (GVHD). In the cross-talk between innate and adaptive immune system, pattern recognition receptors such as Toll-like receptors (TLRs) play a key role. TLRs recognize common protein, carbohydrate or DNA/RNA pattern motifs leading to signaling for cytokine production and T cell and dendritic cell maturation. These receptors may act as tuner of inflammatory and immunologic reactions. Very little is known about the expression and the function of TLRs in vivo in patients who underwent to allogeneic stem cell transplantation (SCT). The aim of this study was to evaluate the expression and the function of TLRs on lymphocytes and monocytes in relation to infection (CMV and HHV-6, especially) and the onset of GVHD.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and methods.</jats:title> <jats:p>The expression of TLRs on T cells and monocytes was analyzed by flow cytometry at day +30, +90, +180 after SCT and at the onset of GVHD. The expression of receptors for lipid-based pathogen-associated molecular patterns (PAMPs: TLR 1,2,4 and 6 surface receptors), receptors for nucleic acid based PAMPs (TLR 3,7,8 and 9 located in cytoplasmic compartments), TLR5 and, TLR10 (surface receptors) was evaluated as mean fluorescence intensity (MFI). Ex vivo induction of cytokines (TNFalpha, MCP1, IFNgamma, IL-10) by TLR ligands was analyzed in the cell supernatant by ELISA. Since the beginning of the study, we have analyzed data of 12 healthy donors and 14 patients. Median age was 46 years (range, 25–64) and 7 patients were male.</jats:p> </jats:sec> <jats:sec> <jats:title>Results.</jats:title> <jats:p>Acute GVHD developed in 7 patients. Patients without acute GVHD after SCT and healthy donors showed different MFI of TLR3 on T cells (5,8±1,4 vs 4,2±1,05 p=0,02), of TLR4 on monocytes (26,1±1,01 vs 15,8±4,9 p=0,004), and of TLR6 on T-lymphocytes (7,3±3,2 vs 4,6±1,1 p=0,02) and monocytes (27±12,1 vs 14,9±4,6 p=0,01). TLR3 expression was significantly decreased on T-lymphocytes and monocytes in patients with acute GVHD in comparison to those without GVHD (4,06±0,8 vs 5,8±1,4 p=0,02; 9,3±7,2 vs 38,02±30 p=0,04). The levels of TLR5 on T cells and monocytes were higher in patients with acute GVHD compared to healthy donors (8,4±2,1 vs 6,4±1,6 p=0,04; 54,2±20,2 vs 33,2±16,5 p=0,04). An increased induction of IFNgamma upon TLR1 ligand activation was observed in patients without GVHD in comparison to healthy donors and patients with GVHD (p=0,04). TLR6 ligand induced significantly the production of IFN gamma in patients with GVHD in comparison to controls and the other patients (p=0,03). Patients without GVHD showed a trend toward a decreased induction of MCP1 upon TLR4 ligand activation (p=0,07). The rate of infections (especially CMV reactivation), clinical and transplant characteristic were not significantly different between patients with and without GVHD.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In our study, a different expression profile of TLRs was found in healthy donors, in patients after SCT without acute GVHD and in those with GVHD. These results suggest that the innate immune response via TLRs activation could be involved in the development of GVHD. The assessment of a larger number of patients would be useful to understand the complex interplay between pathogens, self or non-self DNA and RNA and the immune system after SCT.</jats:p> </jats:sec> <jats:sec> <jats:title>Disclosures:</jats:title> <jats:p>Off Label Use: In Italy the use of azacitidine for Low-risk Myelodysplastic patients is off label. The use of azacitidine in our study is part of a Phase II clinical trial.</jats:p> </jats:sec> |
| doi_str_mv | 10.1182/blood.v116.21.4704.4704 |
| facet_avail | Online, Free |
| finc_class_facet | Biologie, Medizin, Chemie und Pharmazie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52MTE2LjIxLjQ3MDQuNDcwNA |
| imprint | American Society of Hematology, 2010 |
| imprint_str_mv | American Society of Hematology, 2010 |
| institution | DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1 |
| issn | 0006-4971, 1528-0020 |
| issn_str_mv | 0006-4971, 1528-0020 |
| language | English |
| last_indexed | 2024-03-01T10:50:27.065Z |
| match_str | skert2010expressionoftolllikereceptorsonperipheralbloodcellsafterallogeneicstemcelltransplantationongoingresultsofaprospectivestudy |
| mega_collection | American Society of Hematology (CrossRef) |
| physical | 4704-4704 |
| publishDate | 2010 |
| publishDateSort | 2010 |
| publisher | American Society of Hematology |
| record_format | ai |
| recordtype | ai |
| series | Blood |
| source_id | 49 |
| spelling | Skert, Cristina Garrafa, Emirena Fogli, Manuela Fiorentini, Simona Ricotta, Doris Caimi, Luigi Filì, Carla Peli, Annalisa Bergonzi, Cesare Malagola, Michele Giovanni, Martinelli Iacobucci, Ilaria Turra, Alessandro Arpinati, Mario Cattina, Federica Caruso, Arnaldo Russo, Domenico 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v116.21.4704.4704 <jats:title>Abstract</jats:title> <jats:p>Abstract 4704</jats:p> <jats:sec> <jats:title>Background and aim of the study.</jats:title> <jats:p>Emerging trends emphasize the importance of both innate and adaptive immune system in the response against infections, in the pathogenesis of autoimmune diseases and graft-versus-host disease (GVHD). In the cross-talk between innate and adaptive immune system, pattern recognition receptors such as Toll-like receptors (TLRs) play a key role. TLRs recognize common protein, carbohydrate or DNA/RNA pattern motifs leading to signaling for cytokine production and T cell and dendritic cell maturation. These receptors may act as tuner of inflammatory and immunologic reactions. Very little is known about the expression and the function of TLRs in vivo in patients who underwent to allogeneic stem cell transplantation (SCT). The aim of this study was to evaluate the expression and the function of TLRs on lymphocytes and monocytes in relation to infection (CMV and HHV-6, especially) and the onset of GVHD.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and methods.</jats:title> <jats:p>The expression of TLRs on T cells and monocytes was analyzed by flow cytometry at day +30, +90, +180 after SCT and at the onset of GVHD. The expression of receptors for lipid-based pathogen-associated molecular patterns (PAMPs: TLR 1,2,4 and 6 surface receptors), receptors for nucleic acid based PAMPs (TLR 3,7,8 and 9 located in cytoplasmic compartments), TLR5 and, TLR10 (surface receptors) was evaluated as mean fluorescence intensity (MFI). Ex vivo induction of cytokines (TNFalpha, MCP1, IFNgamma, IL-10) by TLR ligands was analyzed in the cell supernatant by ELISA. Since the beginning of the study, we have analyzed data of 12 healthy donors and 14 patients. Median age was 46 years (range, 25–64) and 7 patients were male.</jats:p> </jats:sec> <jats:sec> <jats:title>Results.</jats:title> <jats:p>Acute GVHD developed in 7 patients. Patients without acute GVHD after SCT and healthy donors showed different MFI of TLR3 on T cells (5,8±1,4 vs 4,2±1,05 p=0,02), of TLR4 on monocytes (26,1±1,01 vs 15,8±4,9 p=0,004), and of TLR6 on T-lymphocytes (7,3±3,2 vs 4,6±1,1 p=0,02) and monocytes (27±12,1 vs 14,9±4,6 p=0,01). TLR3 expression was significantly decreased on T-lymphocytes and monocytes in patients with acute GVHD in comparison to those without GVHD (4,06±0,8 vs 5,8±1,4 p=0,02; 9,3±7,2 vs 38,02±30 p=0,04). The levels of TLR5 on T cells and monocytes were higher in patients with acute GVHD compared to healthy donors (8,4±2,1 vs 6,4±1,6 p=0,04; 54,2±20,2 vs 33,2±16,5 p=0,04). An increased induction of IFNgamma upon TLR1 ligand activation was observed in patients without GVHD in comparison to healthy donors and patients with GVHD (p=0,04). TLR6 ligand induced significantly the production of IFN gamma in patients with GVHD in comparison to controls and the other patients (p=0,03). Patients without GVHD showed a trend toward a decreased induction of MCP1 upon TLR4 ligand activation (p=0,07). The rate of infections (especially CMV reactivation), clinical and transplant characteristic were not significantly different between patients with and without GVHD.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In our study, a different expression profile of TLRs was found in healthy donors, in patients after SCT without acute GVHD and in those with GVHD. These results suggest that the innate immune response via TLRs activation could be involved in the development of GVHD. The assessment of a larger number of patients would be useful to understand the complex interplay between pathogens, self or non-self DNA and RNA and the immune system after SCT.</jats:p> </jats:sec> <jats:sec> <jats:title>Disclosures:</jats:title> <jats:p>Off Label Use: In Italy the use of azacitidine for Low-risk Myelodysplastic patients is off label. The use of azacitidine in our study is part of a Phase II clinical trial.</jats:p> </jats:sec> Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study Blood |
| spellingShingle | Skert, Cristina, Garrafa, Emirena, Fogli, Manuela, Fiorentini, Simona, Ricotta, Doris, Caimi, Luigi, Filì, Carla, Peli, Annalisa, Bergonzi, Cesare, Malagola, Michele, Giovanni, Martinelli, Iacobucci, Ilaria, Turra, Alessandro, Arpinati, Mario, Cattina, Federica, Caruso, Arnaldo, Russo, Domenico, Blood, Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_full | Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_fullStr | Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_full_unstemmed | Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_short | Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| title_sort | expression of toll-like receptors on peripheral blood cells after allogeneic stem cell transplantation: ongoing results of a prospective study |
| title_unstemmed | Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood.v116.21.4704.4704 |