| 1. |
- Kissel, Theresa, et al.
(författare)
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IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter : A Cross-Sectional Study Encompassing ~1,500 Samples
- 2022
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 74:7, s. 1147-1158
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti–citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages.Methods: Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up.Results: IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset.Conclusion: The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development.
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| 2. |
- van Wesemael, Tineke J., et al.
(författare)
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Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se : A multicenter cohort study
- 2016
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies. Methods: A population-based Japanese cohort (n = 9575) was used to investigate the association of smoking with RF and anti-cyclic citrullinated peptide antibodies (anti-CCP2) in individuals without RA. Furthermore, RA patients fulfilling the 1987 criteria from three early arthritis cohorts from the Netherlands (n = 678), the United Kingdom (n = 761), and Sweden (n = 795) were used. Data on smoking, RF, anti-CCP2, and anti-CarP were available. A total score of autoantibodies was calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by logistic regression. Results: In the population-based non-RA cohort, no association was found between smoking and one autoantibody (RF or anti-CCP2), but smoking was associated with double-autoantibody positivity (OR 2.95, 95% CI 1.32-6.58). In RA patients, there was no association between smoking and the presence of one autoantibody (OR 0.99, 95% CI 0.78-1.26), but smoking was associated with double-autoantibody positivity (OR 1.32, 95% CI 1.04-1.68) and triple-autoantibody positivity (OR 2.05, 95% CI 1.53-2.73). Conclusions: Smoking is associated with the concurrent presence of multiple RA-associated autoantibodies rather than just ACPA. This indicates that smoking is a risk factor for breaking tolerance to multiple autoantigens in RA.
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| 3. |
- Verheul, Marije K., et al.
(författare)
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Triple positivity for anti–citrullinated protein autoantibodies, rheumatoid factor, and anti–carbamylated protein antibodies conferring high specificity for rheumatoid arthritis : implications for very early identification of at‐risk individuals
- 2018
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Ingår i: Arthritis & Rheumatology. - Hoboken : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70:11, s. 1721-1731
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In rheumatoid arthritis(RA), the autoantibodies anti-citrullinated protein antibodies(ACPA) and rheumatoid factor(RF) are commonly used to aid RA diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPA and RF alone. Also, anti-carbamylated protein(anti-CarP) antibodies have diagnostic and prognostic value as the presence of anti-CarP antibodies associates with joint damage in RA patients and with future RA development in arthralgia patients. Therefore, we aimed to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA.METHODS: A literature search resulted in twelve studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients or healthy controls, in which data on RF, ACPA and anti-CarP antibody-status was available. Random effects meta-analyses were carried out for several antibody combinations.RESULTS: The individual antibodies are highly prevalent in RA(34%-80%) compared to the control groups, but are also present in non-RA controls(0%-23%). To classify most people correctly as RA or non-RA, the combination of ACPA and/or RF often performs well(specificity:65-100, sensitivity:59-88). However, triple positivity for ACPA, RF and anti-CarP antibodies results in a higher specificity(98-100) (accompanied by a lower sensitivity(11-39)).CONCLUSIONS: As the rheumatology field is moving towards very early identification of RA and possible screening for individuals at maximum risk in populations with a low pre-test probability, triple positivity provides interesting information on individuals at risk to develop RA.
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| 7. |
- van der Woude, Diane, et al.
(författare)
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Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:8, s. 1554-1561
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Tidskriftsartikel (refereegranskat)abstract
- Background Anti-citrullinated protein antibodies (ACPA) are the most predictive factor for the development of rheumatoid arthritis (RA). Objective To investigate whether the recognition of citrullinated epitopes changes during disease onset or progression, by studying the fine specificity of ACPA in serum samples collected throughout the disease course, from before the onset of arthritis to longstanding RA. Methods Antibodies recognising five distinct citrullinated antigens were determined by enzyme-linked immunosorbent assay. Serum samples from 36 individuals who had donated blood before and after disease manifestation were used to investigate the development of citrullinated antigen recognition before disease onset. The association of ACPA reactivities with disease outcome was studied using sera from anti-cyclic citrullinated peptide-2 (CCP2)-positive patients with undifferentiated arthritis (UA) who did or did not progress to RA (UA-RA n = 81, or UA-UA n = 35). To investigate the ACPA recognition profile in patients with RA over a prolonged period of time, baseline serum samples from 68 patients were compared with samples obtained 7 years later. Results The number of recognised citrullinated peptides increased in the period preceding disease onset. At the time of disease manifestation, patients with UA who later developed RA recognised significantly more peptides than UA-UA patients. At later stages of the disease course, the ACPA fine specificity did not change. Conclusion Epitope spreading with an increase in the recognition of citrullinated antigens occurs before the onset of RA. Immunological differences in ACPA fine specificity between UA-UA patients and UA-RA patients are present at baseline and are associated with the future disease course.
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