Association of cumulative anti-cyclic citrullinated protein antibodies with radiographic progression in patients with rheumatoid arthritis

Joo, Young Bin; Park, Kyung-Su; Kim, Ki-Jo

doi:10.1007/s10067-019-04554-w

Cited by 12 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Multiple peptide recognition (>3) was not associated with erosive arthritis, in accordance with previous studies that showed that the diversity of recognized epitopes was not associated with the severity of the disease ( 34 , 35 ). Multiple peptide recognition (>3) was associated with a better response to TNF-alpha inhibitors in our cohort.…”

Section: Discussionsupporting

confidence: 91%

In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope

et al. 2021

View full text Add to dashboard Cite

ObjectivesRheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36–50cit, α171–185cit, α501–515cit, α621–635cit, and β60–74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides.Methods184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA.ResultsAnti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044).ConclusionImmune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.

show abstract

Section: Discussionsupporting

confidence: 91%

In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Particularly for our population, the observed seropositivity for ACPAs (>80%), as well as the combined positivity for anti-CCP+/anti-MCV+RF+ (75.1%) is high, especially when compared to that described in other populations where seropositivity oscillates between 38% and 53.9% ( 42 , 46 ). Anti-CCPs positivity is considered a predictive marker for structural joint damage in RA patients ( 47 ), and for higher radiographic and inflammation progression ( 48 – 50 ). In this study, the TTT haplotype of the studied SNPs of the PADI2 gene was associated with a representative score for joint damage, and particularly, the SNP rs2235926 with the ACPAs positivity (anti-CCPs+/anti-MCV+) and ACPAs/RF (anti-CCPs+/anti-MCV+/RF+).…”

Section: Discussionmentioning

confidence: 99%

PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies Serologic Status and Joint Damage in Women from Southern Mexico

et al. 2021

View full text Add to dashboard Cite

The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.

show abstract

“…The following baseline data before initial bDMARD treatment were obtained from medical records and evaluated: patient background data, including age, sex, body mass index, disease duration, smoking history, and complications such as diabetes mellitus (DM) ( 8 ) and anemia ( 9 ); drug-related data, including MTX use, MTX dosage, other csDMARD use, oral prednisolone (PSL) use, oral PSL dosage, and nonsteroidal anti-inflammatory drug use; blood test data, including rheumatoid factor (RF), ACPA, serum matrix metalloproteinase-3 (MMP-3), the neutrophil-to-lymphocyte ratio (NLR), and the estimated glomerular filtration rate.…”

Section: Methodsmentioning

confidence: 99%

“…We developed a formula for predicting an LDA using a logistic regression analysis. The analysis was performed by including three factors predictive of a treatment response to bDMARDs - DAS28-ESR ( 13 - 15 ), serum MMP-3 ( 16 , 17 ), and RF ( 18 , 19 ) - along with DM, which is highly prevalent in elderly RA patients and is a predictor of radiographic progression ( 8 , 20 ). All of these factors were added as covariates to statistically significant factors in the multivariate analysis (p<0.05).…”

Section: Methodsmentioning

confidence: 99%

Scoring Model to Predict a Low Disease Activity in Elderly Rheumatoid Arthritis Patients Initially Treated with Biological Disease-modifying Antirheumatic Drugs

et al. 2021

View full text Add to dashboard Cite

Objective We aimed to develop a scoring model to predict a low disease activity (LDA) in elderly rheumatoid arthritis (RA) patients initially treated with biological disease-modifying antirheumatic drugs (bDMARDs). Methods This retrospective cohort study included 82 elderly RA patients who initially received bDMARDs. The outcome was an LDA after bDMARDs initiation. We developed a predictive formula for an LDA using a multivariate analysis, the accuracy of which was assessed by the area under the curve (AUC) of the receiver operating characteristic curves; the scoring model was developed using the formula. For each factor, approximate odds ratios were scored as an integer, divided into three groups based on the distribution of these scores. In addition, the scoring model accuracy was assessed. Results The mean age was 73.5±6.0 years old, and 86.6% were women. An LDA was achieved in 43 patients (52.4%). The predictive formula for an LDA was prepared using six factors selected for the multivariable analysis: the neutrophil-to-lymphocyte ratio (NLR), anemia, the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR), serum level of matrix metalloproteinase-3 (MMP-3), diabetes mellitus (DM), and rheumatoid factor (RF). The AUC for the formula was 0.829 (95% confidence interval, 0.729-0.930). The odds ratios of the six factors were scored (DAS28-ESR and serum MMP-3=1 point, NLR, anemia, DM, and RF=2 points) and divided into three groups (! 4, 5-7, and " 8). The high-score group (" 8) achieved a positive predictive value of 83%. Conclusion The scoring model accurately predicted an LDA in elderly RA patients initially treated with bDMARDs.

show abstract

Association of cumulative anti-cyclic citrullinated protein antibodies with radiographic progression in patients with rheumatoid arthritis

Cited by 12 publications

References 40 publications

In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope

In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope

PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies Serologic Status and Joint Damage in Women from Southern Mexico

Scoring Model to Predict a Low Disease Activity in Elderly Rheumatoid Arthritis Patients Initially Treated with Biological Disease-modifying Antirheumatic Drugs

Contact Info

Product

Resources

About