Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study
Introduction: Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associate...
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Umeå universitet, Reumatologi
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ftumeauniv:oai:DiVA.org:umu-89506 2024-09-15T18:26:15+00:00 Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study Bokarewa, Maria Brink, Mikael Erlandsson, Malin Rantapää-Dahlqvist, Solbritt 2014 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-89506 https://doi.org/10.1186/ar4474 eng eng UmeÃ¥ universitet, Reumatologi Arthritis Research & Therapy , 2014, 16:1, s. R45- orcid:0000-0001-7675-3488 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-89506 doi:10.1186/ar4474 ISI:000335148700044 Scopus 2-s2.0-84894229251 info:eu-repo/semantics/openAccess Rheumatology and Autoimmunity Reumatologi och inflammation Article in journal info:eu-repo/semantics/article text 2014 ftumeauniv https://doi.org/10.1186/ar4474 2024-07-09T23:37:52Z Introduction: Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruction. Our objective was to investigate the potential of survivin and Flt3L as predictors of RA in samples from patients prior to onset of symptoms. Methods: This study included 47 individuals sampled before onset of RA (median 2.5 years (IQR 4.5) and 155 matched controls, all were donors to the Medical Biobank of Northern Sweden, and 36 RA patients. Levels of anti-CCP, survivin and Flt3L were measured using ELISAs and 29 cytokines/chemokines by multiplex detection. Results: Levels of survivin were increased in pre-symptomatic individuals compared with controls (P = 0.003), whilst the levels of Flt3L were similar. The frequency of survivin positivity in the pre-symptomatic individuals was increased compared with the controls (36.2 vs. 14.2%, P = 0.001) and predicted disease development (odds ratio (OR) = 3.4 (95% confidence interval (CI) 1.6-7.2)). The frequency of survivin and Flt3L in RA patients was increased compared with the controls (both, P < 0.0001, OR = 12.1 (95% CI, 5.3-27.6) and OR = 11.0 (95% CI, 3.9-30.9), respectively). Anti-CCP positive pre-symptomatic individuals and patients had significantly higher levels of survivin compared with anti-CCP2 negative individuals. In pre-symptomatic individuals, survivin correlated with IL-12, IL-1 beta and IL-9 whereas Flt3L correlated to a significantly broader spectrum of cytokines in RA patients. Conclusion: Proto-oncogene survivin was increased in individuals prior to onset of symptoms of RA and was correlated to cytokines suggesting its role at pre-clinical stages of the disease. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Arthritis Research & Therapy 16 1 R45 |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Rheumatology and Autoimmunity Reumatologi och inflammation |
spellingShingle |
Rheumatology and Autoimmunity Reumatologi och inflammation Bokarewa, Maria Brink, Mikael Erlandsson, Malin Rantapää-Dahlqvist, Solbritt Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study |
topic_facet |
Rheumatology and Autoimmunity Reumatologi och inflammation |
description |
Introduction: Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruction. Our objective was to investigate the potential of survivin and Flt3L as predictors of RA in samples from patients prior to onset of symptoms. Methods: This study included 47 individuals sampled before onset of RA (median 2.5 years (IQR 4.5) and 155 matched controls, all were donors to the Medical Biobank of Northern Sweden, and 36 RA patients. Levels of anti-CCP, survivin and Flt3L were measured using ELISAs and 29 cytokines/chemokines by multiplex detection. Results: Levels of survivin were increased in pre-symptomatic individuals compared with controls (P = 0.003), whilst the levels of Flt3L were similar. The frequency of survivin positivity in the pre-symptomatic individuals was increased compared with the controls (36.2 vs. 14.2%, P = 0.001) and predicted disease development (odds ratio (OR) = 3.4 (95% confidence interval (CI) 1.6-7.2)). The frequency of survivin and Flt3L in RA patients was increased compared with the controls (both, P < 0.0001, OR = 12.1 (95% CI, 5.3-27.6) and OR = 11.0 (95% CI, 3.9-30.9), respectively). Anti-CCP positive pre-symptomatic individuals and patients had significantly higher levels of survivin compared with anti-CCP2 negative individuals. In pre-symptomatic individuals, survivin correlated with IL-12, IL-1 beta and IL-9 whereas Flt3L correlated to a significantly broader spectrum of cytokines in RA patients. Conclusion: Proto-oncogene survivin was increased in individuals prior to onset of symptoms of RA and was correlated to cytokines suggesting its role at pre-clinical stages of the disease. |
format |
Article in Journal/Newspaper |
author |
Bokarewa, Maria Brink, Mikael Erlandsson, Malin Rantapää-Dahlqvist, Solbritt |
author_facet |
Bokarewa, Maria Brink, Mikael Erlandsson, Malin Rantapää-Dahlqvist, Solbritt |
author_sort |
Bokarewa, Maria |
title |
Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study |
title_short |
Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study |
title_full |
Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study |
title_fullStr |
Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study |
title_full_unstemmed |
Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study |
title_sort |
survivin but not fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis : a pilot study |
publisher |
Umeå universitet, Reumatologi |
publishDate |
2014 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-89506 https://doi.org/10.1186/ar4474 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Arthritis Research & Therapy , 2014, 16:1, s. R45- orcid:0000-0001-7675-3488 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-89506 doi:10.1186/ar4474 ISI:000335148700044 Scopus 2-s2.0-84894229251 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/ar4474 |
container_title |
Arthritis Research & Therapy |
container_volume |
16 |
container_issue |
1 |
container_start_page |
R45 |
_version_ |
1810466696450801664 |