Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis
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 antibodie...
Published in: | Arthritis Research & Therapy |
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Uppsala universitet, Klinisk immunologi
2016
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Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-280252 https://doi.org/10.1186/s13075-016-0940-2 |
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ftuppsalauniv:oai:DiVA.org:uu-280252 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 K. Trouw, Leendert A. Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapaa-Dahlqvist, Solbritt 2016 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-280252 https://doi.org/10.1186/s13075-016-0940-2 eng eng Uppsala universitet, Klinisk immunologi Umea Univ, Dept Publ Hlth & Clin Med, Div Rheumatol, SE-90185 Umea, Sweden. Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden. Thermo Fisher Sci, Uppsala, Sweden. Umea Univ, Dept Stat, S-90187 Umea, Sweden. Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. Karolinska Inst, Med Inflammat Res Med Biophys & Biochem, Stockholm, Sweden. Arthritis Research & Therapy, 1478-6354, 2016, 18, http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-280252 doi:10.1186/s13075-016-0940-2 PMID 26860413 ISI:000370007700002 info:eu-repo/semantics/openAccess Rheumatoid arthritis Rheumatoid factor Anti-citrullinated peptide antibodies Pre-symptomatic individuals Anti-carbamylated protein antibodies Anti-CCP2 antibodies Immunology Immunologi Article in journal info:eu-repo/semantics/article text 2016 ftuppsalauniv https://doi.org/10.1186/s13075-016-0940-2 2023-02-23T21:47:03Z 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 [a-enolase (CEP-1/Eno(5-21))], fibrinogen (Fib)beta(36-52), Fiba(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 Uppsala University: Publications (DiVA) Elia ENVELOPE(20.166,20.166,70.157,70.157) Arthritis Research & Therapy 18 1 |
institution |
Open Polar |
collection |
Uppsala University: Publications (DiVA) |
op_collection_id |
ftuppsalauniv |
language |
English |
topic |
Rheumatoid arthritis Rheumatoid factor Anti-citrullinated peptide antibodies Pre-symptomatic individuals Anti-carbamylated protein antibodies Anti-CCP2 antibodies Immunology Immunologi |
spellingShingle |
Rheumatoid arthritis Rheumatoid factor Anti-citrullinated peptide antibodies Pre-symptomatic individuals Anti-carbamylated protein antibodies Anti-CCP2 antibodies Immunology Immunologi Brink, Mikael Hansson, Monika Mathsson-Alm, Linda Wijayatunga, Priyantha Verheul, Marije K. Trouw, Leendert A. Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapaa-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 Immunology Immunologi |
description |
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 [a-enolase (CEP-1/Eno(5-21))], fibrinogen (Fib)beta(36-52), Fiba(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 K. Trouw, Leendert A. Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapaa-Dahlqvist, Solbritt |
author_facet |
Brink, Mikael Hansson, Monika Mathsson-Alm, Linda Wijayatunga, Priyantha Verheul, Marije K. Trouw, Leendert A. Holmdahl, Rikard Rönnelid, Johan Klareskog, Lars Rantapaa-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 |
Uppsala universitet, Klinisk immunologi |
publishDate |
2016 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-280252 https://doi.org/10.1186/s13075-016-0940-2 |
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 |
Arthritis Research & Therapy, 1478-6354, 2016, 18, http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-280252 doi:10.1186/s13075-016-0940-2 PMID 26860413 ISI:000370007700002 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/s13075-016-0940-2 |
container_title |
Arthritis Research & Therapy |
container_volume |
18 |
container_issue |
1 |
_version_ |
1766147904827817984 |