Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes
Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap be...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Sighart, R. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017 |
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| Schlagwörter: |
Hereditary periodic fever syndromes |
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| Anmerkung: |
© Springer-Verlag GmbH Germany, part of Springer Nature 2017 |
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| Übergeordnetes Werk: |
Enthalten in: Rheumatology international - Berlin : Springer, 1981, 38(2017), 1 vom: 20. Nov., Seite 111-120 |
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| Übergeordnetes Werk: |
volume:38 ; year:2017 ; number:1 ; day:20 ; month:11 ; pages:111-120 |
| Links: |
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| DOI / URN: |
10.1007/s00296-017-3885-0 |
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| Katalog-ID: |
SPR003871711 |
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| 500 | |a © Springer-Verlag GmbH Germany, part of Springer Nature 2017 | ||
| 520 | |a Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. | ||
| 650 | 4 | |a Adult onset Still’s disease |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a Familial Mediterranean fever |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Hereditary periodic fever syndromes |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a TNF receptor-associated periodic syndrome |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Autoinflammatory syndromes |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Hüffmeier, U. |0 (orcid)0000-0001-6448-4671 |4 aut | |
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10.1007/s00296-017-3885-0 doi (DE-627)SPR003871711 (SPR)s00296-017-3885-0-e DE-627 ger DE-627 rakwb eng Sighart, R. verfasserin aut Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2017 Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. Adult onset Still’s disease (dpeaa)DE-He213 Biological therapy (dpeaa)DE-He213 Familial Mediterranean fever (dpeaa)DE-He213 Hereditary periodic fever syndromes (dpeaa)DE-He213 TNF receptor-associated periodic syndrome (dpeaa)DE-He213 Autoinflammatory syndromes (dpeaa)DE-He213 Rech, J. (orcid)0000-0002-2569-2029 aut Hueber, A. (orcid)0000-0001-6454-1234 aut Blank, N. (orcid)0000-0002-9419-1690 aut Löhr, S. (orcid)0000-0001-7720-0762 aut Reis, A. (orcid)0000-0002-6301-6363 aut Sticht, H. (orcid)0000-0001-5644-045X aut Hüffmeier, U. (orcid)0000-0001-6448-4671 aut Enthalten in Rheumatology international Berlin : Springer, 1981 38(2017), 1 vom: 20. Nov., Seite 111-120 (DE-627)265508320 (DE-600)1464208-6 1437-160X nnns volume:38 year:2017 number:1 day:20 month:11 pages:111-120 https://dx.doi.org/10.1007/s00296-017-3885-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 38 2017 1 20 11 111-120 |
| spelling |
10.1007/s00296-017-3885-0 doi (DE-627)SPR003871711 (SPR)s00296-017-3885-0-e DE-627 ger DE-627 rakwb eng Sighart, R. verfasserin aut Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2017 Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. Adult onset Still’s disease (dpeaa)DE-He213 Biological therapy (dpeaa)DE-He213 Familial Mediterranean fever (dpeaa)DE-He213 Hereditary periodic fever syndromes (dpeaa)DE-He213 TNF receptor-associated periodic syndrome (dpeaa)DE-He213 Autoinflammatory syndromes (dpeaa)DE-He213 Rech, J. (orcid)0000-0002-2569-2029 aut Hueber, A. (orcid)0000-0001-6454-1234 aut Blank, N. (orcid)0000-0002-9419-1690 aut Löhr, S. (orcid)0000-0001-7720-0762 aut Reis, A. (orcid)0000-0002-6301-6363 aut Sticht, H. (orcid)0000-0001-5644-045X aut Hüffmeier, U. (orcid)0000-0001-6448-4671 aut Enthalten in Rheumatology international Berlin : Springer, 1981 38(2017), 1 vom: 20. Nov., Seite 111-120 (DE-627)265508320 (DE-600)1464208-6 1437-160X nnns volume:38 year:2017 number:1 day:20 month:11 pages:111-120 https://dx.doi.org/10.1007/s00296-017-3885-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 38 2017 1 20 11 111-120 |
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10.1007/s00296-017-3885-0 doi (DE-627)SPR003871711 (SPR)s00296-017-3885-0-e DE-627 ger DE-627 rakwb eng Sighart, R. verfasserin aut Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2017 Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. Adult onset Still’s disease (dpeaa)DE-He213 Biological therapy (dpeaa)DE-He213 Familial Mediterranean fever (dpeaa)DE-He213 Hereditary periodic fever syndromes (dpeaa)DE-He213 TNF receptor-associated periodic syndrome (dpeaa)DE-He213 Autoinflammatory syndromes (dpeaa)DE-He213 Rech, J. (orcid)0000-0002-2569-2029 aut Hueber, A. (orcid)0000-0001-6454-1234 aut Blank, N. (orcid)0000-0002-9419-1690 aut Löhr, S. (orcid)0000-0001-7720-0762 aut Reis, A. (orcid)0000-0002-6301-6363 aut Sticht, H. (orcid)0000-0001-5644-045X aut Hüffmeier, U. (orcid)0000-0001-6448-4671 aut Enthalten in Rheumatology international Berlin : Springer, 1981 38(2017), 1 vom: 20. Nov., Seite 111-120 (DE-627)265508320 (DE-600)1464208-6 1437-160X nnns volume:38 year:2017 number:1 day:20 month:11 pages:111-120 https://dx.doi.org/10.1007/s00296-017-3885-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 38 2017 1 20 11 111-120 |
| allfieldsGer |
10.1007/s00296-017-3885-0 doi (DE-627)SPR003871711 (SPR)s00296-017-3885-0-e DE-627 ger DE-627 rakwb eng Sighart, R. verfasserin aut Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2017 Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. Adult onset Still’s disease (dpeaa)DE-He213 Biological therapy (dpeaa)DE-He213 Familial Mediterranean fever (dpeaa)DE-He213 Hereditary periodic fever syndromes (dpeaa)DE-He213 TNF receptor-associated periodic syndrome (dpeaa)DE-He213 Autoinflammatory syndromes (dpeaa)DE-He213 Rech, J. (orcid)0000-0002-2569-2029 aut Hueber, A. (orcid)0000-0001-6454-1234 aut Blank, N. (orcid)0000-0002-9419-1690 aut Löhr, S. (orcid)0000-0001-7720-0762 aut Reis, A. (orcid)0000-0002-6301-6363 aut Sticht, H. (orcid)0000-0001-5644-045X aut Hüffmeier, U. (orcid)0000-0001-6448-4671 aut Enthalten in Rheumatology international Berlin : Springer, 1981 38(2017), 1 vom: 20. Nov., Seite 111-120 (DE-627)265508320 (DE-600)1464208-6 1437-160X nnns volume:38 year:2017 number:1 day:20 month:11 pages:111-120 https://dx.doi.org/10.1007/s00296-017-3885-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 38 2017 1 20 11 111-120 |
| allfieldsSound |
10.1007/s00296-017-3885-0 doi (DE-627)SPR003871711 (SPR)s00296-017-3885-0-e DE-627 ger DE-627 rakwb eng Sighart, R. verfasserin aut Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2017 Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. Adult onset Still’s disease (dpeaa)DE-He213 Biological therapy (dpeaa)DE-He213 Familial Mediterranean fever (dpeaa)DE-He213 Hereditary periodic fever syndromes (dpeaa)DE-He213 TNF receptor-associated periodic syndrome (dpeaa)DE-He213 Autoinflammatory syndromes (dpeaa)DE-He213 Rech, J. (orcid)0000-0002-2569-2029 aut Hueber, A. (orcid)0000-0001-6454-1234 aut Blank, N. (orcid)0000-0002-9419-1690 aut Löhr, S. (orcid)0000-0001-7720-0762 aut Reis, A. (orcid)0000-0002-6301-6363 aut Sticht, H. (orcid)0000-0001-5644-045X aut Hüffmeier, U. (orcid)0000-0001-6448-4671 aut Enthalten in Rheumatology international Berlin : Springer, 1981 38(2017), 1 vom: 20. Nov., Seite 111-120 (DE-627)265508320 (DE-600)1464208-6 1437-160X nnns volume:38 year:2017 number:1 day:20 month:11 pages:111-120 https://dx.doi.org/10.1007/s00296-017-3885-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 38 2017 1 20 11 111-120 |
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Enthalten in Rheumatology international 38(2017), 1 vom: 20. Nov., Seite 111-120 volume:38 year:2017 number:1 day:20 month:11 pages:111-120 |
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Enthalten in Rheumatology international 38(2017), 1 vom: 20. Nov., Seite 111-120 volume:38 year:2017 number:1 day:20 month:11 pages:111-120 |
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Adult onset Still’s disease Biological therapy Familial Mediterranean fever Hereditary periodic fever syndromes TNF receptor-associated periodic syndrome Autoinflammatory syndromes |
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Sighart, R. @@aut@@ Rech, J. @@aut@@ Hueber, A. @@aut@@ Blank, N. @@aut@@ Löhr, S. @@aut@@ Reis, A. @@aut@@ Sticht, H. @@aut@@ Hüffmeier, U. @@aut@@ |
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Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Adult onset Still’s disease</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Biological therapy</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Familial Mediterranean fever</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hereditary periodic fever syndromes</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">TNF receptor-associated periodic syndrome</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Autoinflammatory syndromes</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rech, J.</subfield><subfield code="0">(orcid)0000-0002-2569-2029</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hueber, A.</subfield><subfield code="0">(orcid)0000-0001-6454-1234</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Blank, N.</subfield><subfield code="0">(orcid)0000-0002-9419-1690</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Löhr, S.</subfield><subfield code="0">(orcid)0000-0001-7720-0762</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Reis, A.</subfield><subfield code="0">(orcid)0000-0002-6301-6363</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sticht, H.</subfield><subfield code="0">(orcid)0000-0001-5644-045X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hüffmeier, U.</subfield><subfield code="0">(orcid)0000-0001-6448-4671</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Rheumatology international</subfield><subfield code="d">Berlin : Springer, 1981</subfield><subfield code="g">38(2017), 1 vom: 20. 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Sighart, R. |
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Sighart, R. misc Adult onset Still’s disease misc Biological therapy misc Familial Mediterranean fever misc Hereditary periodic fever syndromes misc TNF receptor-associated periodic syndrome misc Autoinflammatory syndromes Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes |
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Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes Adult onset Still’s disease (dpeaa)DE-He213 Biological therapy (dpeaa)DE-He213 Familial Mediterranean fever (dpeaa)DE-He213 Hereditary periodic fever syndromes (dpeaa)DE-He213 TNF receptor-associated periodic syndrome (dpeaa)DE-He213 Autoinflammatory syndromes (dpeaa)DE-He213 |
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misc Adult onset Still’s disease misc Biological therapy misc Familial Mediterranean fever misc Hereditary periodic fever syndromes misc TNF receptor-associated periodic syndrome misc Autoinflammatory syndromes |
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evidence for genetic overlap between adult onset still’s disease and hereditary periodic fever syndromes |
| title_auth |
Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes |
| abstract |
Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. © Springer-Verlag GmbH Germany, part of Springer Nature 2017 |
| abstractGer |
Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. © Springer-Verlag GmbH Germany, part of Springer Nature 2017 |
| abstract_unstemmed |
Objective Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. Methods We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pc = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (pc = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients. © Springer-Verlag GmbH Germany, part of Springer Nature 2017 |
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Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes |
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| score |
7.4003916 |