Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis
Introduction: It has previously been shown that an increased number of antibodies against citrullinated peptides/proteins (ACPA) predate the onset of rheumatoid arthritis (RA). Over time antibody positivity expands, involving more specific responses when approaching the onset of symptoms. We investi...
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Umeå universitet, Reumatologi
2015
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ftumeauniv:oai:DiVA.org:umu-106129 2024-09-15T18:26:16+00:00 Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis Kokkonen, Heidi Brink, Mikael Hansson, Monika Lassen, Ewa Mathsson-Alm, Linda Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt 2015 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-106129 https://doi.org/10.1186/s13075-015-0638-x eng eng UmeÃ¥ universitet, Reumatologi Stockholm, Sweden Uppsala, Sweden Arthritis Research & Therapy , 2015, 17, orcid:0000-0001-7675-3488 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-106129 doi:10.1186/s13075-015-0638-x PMID 25990747 ISI:000354850400001 Scopus 2-s2.0-84930505619 info:eu-repo/semantics/openAccess Rheumatology and Autoimmunity Reumatologi och inflammation Article in journal info:eu-repo/semantics/article text 2015 ftumeauniv https://doi.org/10.1186/s13075-015-0638-x 2024-07-09T23:37:52Z Introduction: It has previously been shown that an increased number of antibodies against citrullinated peptides/proteins (ACPA) predate the onset of rheumatoid arthritis (RA). Over time antibody positivity expands, involving more specific responses when approaching the onset of symptoms. We investigated the impact of human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking on the development of ACPA, as well as in combination with ACPA during the state of quiescent autoimmunity (before the onset of symptoms), on the development of RA. Methods: Blood samples donated to the Medical Biobank of Northern Sweden from individuals prior to the onset of symptoms of RA (n = 370) and after onset (n = 203) and from population-based controls (n = 585) were used. Antibodies against 10 citrullinated peptides, fibrinogen (Fib alpha 561-583, alpha 580-600, beta 62-81a, beta 62-81b, beta 36-52), vimentin (Vim2-17, 60-75), filaggrin (CCP-1/Fil307-324),alpha-enolase (CEP-1/Eno5-21), collagen type II (citC1359-369), and anti-cyclic citrullinated peptide (CCP) 2 antibodies were analysed. Results: HLA-SE-positive individuals were more frequently positive for ACPA compared with HLA-SE-negative individuals prior to the onset of symptoms of RA, particularly for antibodies against CEP-1 and Fib beta 62-81a (72). Smoking was associated with antibodies against Vim2-17 and citC1359-369. HLA-SE and smoking showed increasing association to the presence of the antibodies closer to disease onset. The highest odds ratio (OR) for development of RA was for the combination of HLA-SE alleles and ACPA positivity, especially for antibodies against Fib beta 62-81b, CCP-1/Fil307-324, and Fib beta 36-52. A gene-environment additive interaction between smoking and HLA-SE alleles for the risk of disease development was found, with the highest OR for individuals positive for antibodies against Fib beta 36-52, CEP-1, and Fib alpha 580-600. Conclusions: The relationships between antibodies against the different ACPA specificities, HLA-SE, and ... Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Arthritis Research & Therapy 17 1 |
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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 Kokkonen, Heidi Brink, Mikael Hansson, Monika Lassen, Ewa Mathsson-Alm, Linda Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis |
topic_facet |
Rheumatology and Autoimmunity Reumatologi och inflammation |
description |
Introduction: It has previously been shown that an increased number of antibodies against citrullinated peptides/proteins (ACPA) predate the onset of rheumatoid arthritis (RA). Over time antibody positivity expands, involving more specific responses when approaching the onset of symptoms. We investigated the impact of human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking on the development of ACPA, as well as in combination with ACPA during the state of quiescent autoimmunity (before the onset of symptoms), on the development of RA. Methods: Blood samples donated to the Medical Biobank of Northern Sweden from individuals prior to the onset of symptoms of RA (n = 370) and after onset (n = 203) and from population-based controls (n = 585) were used. Antibodies against 10 citrullinated peptides, fibrinogen (Fib alpha 561-583, alpha 580-600, beta 62-81a, beta 62-81b, beta 36-52), vimentin (Vim2-17, 60-75), filaggrin (CCP-1/Fil307-324),alpha-enolase (CEP-1/Eno5-21), collagen type II (citC1359-369), and anti-cyclic citrullinated peptide (CCP) 2 antibodies were analysed. Results: HLA-SE-positive individuals were more frequently positive for ACPA compared with HLA-SE-negative individuals prior to the onset of symptoms of RA, particularly for antibodies against CEP-1 and Fib beta 62-81a (72). Smoking was associated with antibodies against Vim2-17 and citC1359-369. HLA-SE and smoking showed increasing association to the presence of the antibodies closer to disease onset. The highest odds ratio (OR) for development of RA was for the combination of HLA-SE alleles and ACPA positivity, especially for antibodies against Fib beta 62-81b, CCP-1/Fil307-324, and Fib beta 36-52. A gene-environment additive interaction between smoking and HLA-SE alleles for the risk of disease development was found, with the highest OR for individuals positive for antibodies against Fib beta 36-52, CEP-1, and Fib alpha 580-600. Conclusions: The relationships between antibodies against the different ACPA specificities, HLA-SE, and ... |
format |
Article in Journal/Newspaper |
author |
Kokkonen, Heidi Brink, Mikael Hansson, Monika Lassen, Ewa Mathsson-Alm, Linda Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt |
author_facet |
Kokkonen, Heidi Brink, Mikael Hansson, Monika Lassen, Ewa Mathsson-Alm, Linda Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt |
author_sort |
Kokkonen, Heidi |
title |
Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis |
title_short |
Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis |
title_full |
Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis |
title_fullStr |
Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis |
title_full_unstemmed |
Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis |
title_sort |
associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis |
publisher |
Umeå universitet, Reumatologi |
publishDate |
2015 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-106129 https://doi.org/10.1186/s13075-015-0638-x |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Arthritis Research & Therapy , 2015, 17, orcid:0000-0001-7675-3488 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-106129 doi:10.1186/s13075-015-0638-x PMID 25990747 ISI:000354850400001 Scopus 2-s2.0-84930505619 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/s13075-015-0638-x |
container_title |
Arthritis Research & Therapy |
container_volume |
17 |
container_issue |
1 |
_version_ |
1810466713688342528 |