Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis
Abstract Background The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these a...
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ftbiomed:oai:biomedcentral.com:s13075-016-0940-2 2023-05-15T17:45:08+02:00 Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis Brink, Mikael Hansson, Monika Mathsson-Alm, Linda Wijayatunga, Priyantha Verheul, Marije Trouw, Leendert Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt 2016-02-09 http://arthritis-research.com/content/18/1/43 en eng BioMed Central Ltd. http://arthritis-research.com/content/18/1/43 Copyright 2016 Brink et al. Rheumatoid arthritis Rheumatoid factor Anti-citrullinated peptide antibodies Pre-symptomatic individuals Anti-carbamylated protein antibodies Anti-CCP2 antibodies Research article 2016 ftbiomed 2016-02-14T01:00:21Z Abstract Background The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. Methods Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. Results The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects ( p < 0.0001). In samples collected ≥15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [α-enolase (CEP-1/Eno 5–21 )], fibrinogen (Fib)β 36–52 , Fibα 580–600 , filaggrin (CCP-1/Fil 307–324 ) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms ( p < 0.001–0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. Conclusions RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies. Article in Journal/Newspaper Northern Sweden BioMed Central Elia ENVELOPE(20.166,20.166,70.157,70.157) |
institution |
Open Polar |
collection |
BioMed Central |
op_collection_id |
ftbiomed |
language |
English |
topic |
Rheumatoid arthritis Rheumatoid factor Anti-citrullinated peptide antibodies Pre-symptomatic individuals Anti-carbamylated protein antibodies Anti-CCP2 antibodies |
spellingShingle |
Rheumatoid arthritis Rheumatoid factor Anti-citrullinated peptide antibodies Pre-symptomatic individuals Anti-carbamylated protein antibodies Anti-CCP2 antibodies Brink, Mikael Hansson, Monika Mathsson-Alm, Linda Wijayatunga, Priyantha Verheul, Marije Trouw, Leendert Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis |
topic_facet |
Rheumatoid arthritis Rheumatoid factor Anti-citrullinated peptide antibodies Pre-symptomatic individuals Anti-carbamylated protein antibodies Anti-CCP2 antibodies |
description |
Abstract Background The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. Methods Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. Results The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects ( p < 0.0001). In samples collected ≥15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [α-enolase (CEP-1/Eno 5–21 )], fibrinogen (Fib)β 36–52 , Fibα 580–600 , filaggrin (CCP-1/Fil 307–324 ) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms ( p < 0.001–0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. Conclusions RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies. |
format |
Article in Journal/Newspaper |
author |
Brink, Mikael Hansson, Monika Mathsson-Alm, Linda Wijayatunga, Priyantha Verheul, Marije Trouw, Leendert Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt |
author_facet |
Brink, Mikael Hansson, Monika Mathsson-Alm, Linda Wijayatunga, Priyantha Verheul, Marije Trouw, Leendert Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapää-Dahlqvist, Solbritt |
author_sort |
Brink, Mikael |
title |
Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis |
title_short |
Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis |
title_full |
Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis |
title_fullStr |
Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis |
title_full_unstemmed |
Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis |
title_sort |
rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis |
publisher |
BioMed Central Ltd. |
publishDate |
2016 |
url |
http://arthritis-research.com/content/18/1/43 |
long_lat |
ENVELOPE(20.166,20.166,70.157,70.157) |
geographic |
Elia |
geographic_facet |
Elia |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
http://arthritis-research.com/content/18/1/43 |
op_rights |
Copyright 2016 Brink et al. |
_version_ |
1766147906317844480 |