The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome
Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely...
Ausführliche Beschreibung
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| Autor*in: |
de Koning, Heleen D. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015 |
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| Schlagwörter: |
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| Anmerkung: |
© de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
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| Übergeordnetes Werk: |
Enthalten in: Arthritis Research & Therapy - London : BioMed Central, 1999, 17(2015), 1 vom: 22. Juli |
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| Übergeordnetes Werk: |
volume:17 ; year:2015 ; number:1 ; day:22 ; month:07 |
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| DOI / URN: |
10.1186/s13075-015-0696-0 |
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| Katalog-ID: |
SPR030217512 |
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| 520 | |a Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. | ||
| 650 | 4 | |a Anakinra |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a Symptomatic Phase |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a S100A12 Level |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Schalkwijk, Joost |4 aut | |
| 700 | 1 | |a Stoffels, Monique |4 aut | |
| 700 | 1 | |a Jongekrijg, Johanna |4 aut | |
| 700 | 1 | |a Jacobs, Joannes F. M. |4 aut | |
| 700 | 1 | |a Verwiel, Eugène |4 aut | |
| 700 | 1 | |a Koenen, Hans J. P. M. |4 aut | |
| 700 | 1 | |a Preijers, Frank |4 aut | |
| 700 | 1 | |a Holzinger, Dirk |4 aut | |
| 700 | 1 | |a Joosten, Irma |4 aut | |
| 700 | 1 | |a van der Meer, Jos W. M. |4 aut | |
| 700 | 1 | |a Simon, Anna |4 aut | |
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10.1186/s13075-015-0696-0 doi (DE-627)SPR030217512 (SPR)s13075-015-0696-0-e DE-627 ger DE-627 rakwb eng de Koning, Heleen D. verfasserin aut The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. Anakinra (dpeaa)DE-He213 Ethylene Glycol Tetraacetic Acid (dpeaa)DE-He213 Canakinumab (dpeaa)DE-He213 Symptomatic Phase (dpeaa)DE-He213 S100A12 Level (dpeaa)DE-He213 Schalkwijk, Joost aut Stoffels, Monique aut Jongekrijg, Johanna aut Jacobs, Joannes F. M. aut Verwiel, Eugène aut Koenen, Hans J. P. M. aut Preijers, Frank aut Holzinger, Dirk aut Joosten, Irma aut van der Meer, Jos W. M. aut Simon, Anna aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 17(2015), 1 vom: 22. Juli (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:17 year:2015 number:1 day:22 month:07 https://dx.doi.org/10.1186/s13075-015-0696-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 22 07 |
| spelling |
10.1186/s13075-015-0696-0 doi (DE-627)SPR030217512 (SPR)s13075-015-0696-0-e DE-627 ger DE-627 rakwb eng de Koning, Heleen D. verfasserin aut The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. Anakinra (dpeaa)DE-He213 Ethylene Glycol Tetraacetic Acid (dpeaa)DE-He213 Canakinumab (dpeaa)DE-He213 Symptomatic Phase (dpeaa)DE-He213 S100A12 Level (dpeaa)DE-He213 Schalkwijk, Joost aut Stoffels, Monique aut Jongekrijg, Johanna aut Jacobs, Joannes F. M. aut Verwiel, Eugène aut Koenen, Hans J. P. M. aut Preijers, Frank aut Holzinger, Dirk aut Joosten, Irma aut van der Meer, Jos W. M. aut Simon, Anna aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 17(2015), 1 vom: 22. Juli (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:17 year:2015 number:1 day:22 month:07 https://dx.doi.org/10.1186/s13075-015-0696-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 22 07 |
| allfields_unstemmed |
10.1186/s13075-015-0696-0 doi (DE-627)SPR030217512 (SPR)s13075-015-0696-0-e DE-627 ger DE-627 rakwb eng de Koning, Heleen D. verfasserin aut The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. Anakinra (dpeaa)DE-He213 Ethylene Glycol Tetraacetic Acid (dpeaa)DE-He213 Canakinumab (dpeaa)DE-He213 Symptomatic Phase (dpeaa)DE-He213 S100A12 Level (dpeaa)DE-He213 Schalkwijk, Joost aut Stoffels, Monique aut Jongekrijg, Johanna aut Jacobs, Joannes F. M. aut Verwiel, Eugène aut Koenen, Hans J. P. M. aut Preijers, Frank aut Holzinger, Dirk aut Joosten, Irma aut van der Meer, Jos W. M. aut Simon, Anna aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 17(2015), 1 vom: 22. Juli (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:17 year:2015 number:1 day:22 month:07 https://dx.doi.org/10.1186/s13075-015-0696-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 22 07 |
| allfieldsGer |
10.1186/s13075-015-0696-0 doi (DE-627)SPR030217512 (SPR)s13075-015-0696-0-e DE-627 ger DE-627 rakwb eng de Koning, Heleen D. verfasserin aut The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. Anakinra (dpeaa)DE-He213 Ethylene Glycol Tetraacetic Acid (dpeaa)DE-He213 Canakinumab (dpeaa)DE-He213 Symptomatic Phase (dpeaa)DE-He213 S100A12 Level (dpeaa)DE-He213 Schalkwijk, Joost aut Stoffels, Monique aut Jongekrijg, Johanna aut Jacobs, Joannes F. M. aut Verwiel, Eugène aut Koenen, Hans J. P. M. aut Preijers, Frank aut Holzinger, Dirk aut Joosten, Irma aut van der Meer, Jos W. M. aut Simon, Anna aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 17(2015), 1 vom: 22. Juli (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:17 year:2015 number:1 day:22 month:07 https://dx.doi.org/10.1186/s13075-015-0696-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 22 07 |
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10.1186/s13075-015-0696-0 doi (DE-627)SPR030217512 (SPR)s13075-015-0696-0-e DE-627 ger DE-627 rakwb eng de Koning, Heleen D. verfasserin aut The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. Anakinra (dpeaa)DE-He213 Ethylene Glycol Tetraacetic Acid (dpeaa)DE-He213 Canakinumab (dpeaa)DE-He213 Symptomatic Phase (dpeaa)DE-He213 S100A12 Level (dpeaa)DE-He213 Schalkwijk, Joost aut Stoffels, Monique aut Jongekrijg, Johanna aut Jacobs, Joannes F. M. aut Verwiel, Eugène aut Koenen, Hans J. P. M. aut Preijers, Frank aut Holzinger, Dirk aut Joosten, Irma aut van der Meer, Jos W. M. aut Simon, Anna aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 17(2015), 1 vom: 22. Juli (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:17 year:2015 number:1 day:22 month:07 https://dx.doi.org/10.1186/s13075-015-0696-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2015 1 22 07 |
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The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome |
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Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
| abstractGer |
Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
| abstract_unstemmed |
Introduction Schnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses. Methods Eight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls. Results IL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients. Conclusions In conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS. © de Koning et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
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The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome |
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Schalkwijk, Joost Stoffels, Monique Jongekrijg, Johanna Jacobs, Joannes F. M. Verwiel, Eugène Koenen, Hans J. P. M. Preijers, Frank Holzinger, Dirk Joosten, Irma van der Meer, Jos W. M. Simon, Anna |
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Schalkwijk, Joost Stoffels, Monique Jongekrijg, Johanna Jacobs, Joannes F. M. Verwiel, Eugène Koenen, Hans J. P. M. Preijers, Frank Holzinger, Dirk Joosten, Irma van der Meer, Jos W. M. Simon, Anna |
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