Novel autoantibodies identified in ACPA-negative rheumatoid arthritis

2021 ◽  
pp. annrheumdis-2020-218460
Author(s):  
Ketian Li ◽  
Wenxiu Mo ◽  
Lijun Wu ◽  
Xunyao Wu ◽  
Cainan Luo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Diagnosis ◽  
Protein Microarray ◽  
Healthy Controls ◽  
Microarray Technology ◽  
Validation And Verification ◽  
Human Proteins ◽  
Diagnostic Values ◽  
Acpa Status ◽  
Citrullinated Protein

ObjectivesLack of effective biomarkers in anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA) impedes early diagnosis and treatment. This study aimed to identify novel autoantibodies in RA and verify their diagnostic values in ACPA-negative RA based on protein microarray technology.MethodsA total of 1011 sera from 559 RA (276 ACPA-positive and 283 ACPA-negative), 239 disease controls (DCs) and 213 healthy controls (HCs) were collected and sampled on two sequential microarrays and ELISA and western blot (WB) detection, for novel autoantibodies discovery, validation and verification, respectively. The high-density protein microarray printed with a broad spectrum of recombinant human proteins was first employed to screen candidate autoantibodies, then focused microarrays composed of candidate autoantigens were used for validation, followed by ELISA and WB to verify the presence of the most promising candidates in ACPA-negative RA.ResultsNine novel autoantibodies were identified by two sequential microarrays with positivity 17.93%–27.59% and specificities >90% in ACPA-negative RA. Among these, anti-PTX3 and anti-DUSP11 autoantibodies presented with the highest sensitivity and were consistently verified by ELISA and WB. Pooling samples of all cohorts, the positivities of anti-PTX3 and anti-DUSP11 in ACPA-negative RA were 27.56% and 31.80%, respectively, similar to those in ACPA-positive RA, and significantly higher than in HCs (4.69% and 2.35%) and DCs (10.04% and 8.49%) (p<0.0001). Combination of anti-PTX3 with anti-DUSP11 significantly increased the diagnostic sensitivity (38.00%) with specificity of 88.72%, regardless of ACPA status.ConclusionAnti-PTX3 and anti-DUSP11 autoantibodies are newly identified biomarkers for diagnosis of ACPA-negative RA.

scholarly journals Association Between STAT4 rs7574865 Polymorphism and Rheumatoid Arthritis: Debate Unresolved

2018 ◽  
Vol 12 (1) ◽  
pp. 172-178
Author(s):  
Iman Tarakji ◽  
Wafa Habbal ◽  
Fawza Monem
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Factors ◽  
Shared Epitope ◽  
Direct Sequencing ◽  
Healthy Controls ◽  
Asian Populations ◽  
Genotype Frequencies ◽  
Potential Impact ◽  
Acpa Status ◽  
Citrullinated Protein

Background: STAT4 rs7574865 polymorphism has been evidently associated with susceptibility to Rheumatoid Arthritis (RA) in European and Eastern Asian populations, whereas studies in other countries reported otherwise. Objective: We investigated the distribution of STAT4 rs7574865 polymorphism in a group of Syrian RA patients. Methods: Eighty-one RA patients and forty healthy controls were enrolled and STAT4 rs7574865 was genotyped by direct sequencing. RA patients were stratified according to Anti-Citrullinated Protein Antibodies (ACPA) status for analysis. Results: Minor T allele frequencies were 30.4%, 16.7%, and 23.8% in ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls, respectively. No significant differences in STAT4 rs7574865 allele/genotype frequencies were found between ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls (P>0.05). Conclusion: STAT4 rs7574865 TT genotype showed a potential impact on ACPA positivity in Syrian RA patients. However, STAT4 rs7574865 effect on RA onset and severity is minor compared to other genetic factors such as HLA-DRB1 shared epitope alleles.

scholarly journals SAT0012 ANTIBODY REACTIVITY AGAINST NATIVE PROTEINS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 936.2-936
Author(s):  
T. B. G. Poulsen ◽  
D. Damgaard ◽  
M. M. Jørgensen ◽  
L. Senolt ◽  
J. Blackburn ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Histone Deacetylases ◽  
Protein Microarray ◽  
Treatment Modalities ◽  
Igg Antibodies ◽  
Calcium Calmodulin Dependent ◽  
Native Proteins ◽  
Healthy Donors ◽  
Human Proteins ◽  
Dependent Protein

Background:The majority of patients with rheumatoid arthritis (RA) produce autoantibodies against proteins that have undergone post-translational modfication, e.g. citrullination or carbamylation. There is growing evidence of their relevance and their potential utility to improve diagnosis, patient stratification, and prognosis for precision medicine. Investigating new autoantibody patterns may allow further stratification of patients and identifying subsets of patients that benefit from different treatment modalities. Following the discovery of high autoantibody reactivity against multiple modified proteins the interest in native targets decreased. Even though antibodies reacting with native proteins may also have a role in RA pathogenesis, their reactivity patterns are much less studied.Objectives:To identify novel native autoantigens in RA patients and elucidate patterns within autoantibody reactivity against native autoantigens.Methods:We investigated the reactivity of autoantibodies in plasma pools from 15 anti-CCP positive and 10 anti-CCP negative RA patients and 10 healthy donors against more than 1600 human proteins in native configuration using the Immunome high-density protein microarray.Results:We identified 86 native proteins that were recognized by IgG antibodies from anti-CCP positive RA patients and 76 native proteins recognized by IgG antibodies from anti-CCP negative RA patients, but not by antibodies from healthy donors. Examples of proteins recognized by both patient subgroups are calcium/calmodulin-dependent protein kinase type II subunits, histone deacetylases, keratin, and vimentin. Reactivity against the ribonucleic protein SSB was observed in anti-CCP negative RA patients only.Conclusion:Several human proteins in their native conformation are recognized by autoantibodies from anti-CCP positive as well as anti-CCP negative RA patients. In general, anti-CCP positive patients had higher autoantibody activity than anti-CCP negative patients and healthy donors.References:[1] Konig, M.F., Giles, J.T., Nigrovic, P.A., Andrade, F., 2016. Antibodies to native and citrullinated RA33 (hnRNP A2/B1) challenge citrullination as the inciting principle underlying loss of tolerance in rheumatoid arthritis. Ann. Rheum. Dis. 75, 2022–2028.[2] Zheng, Z., Mergaert, A.M., Fahmy, L.M., Bawadekar, M., Holmes, C.L., Ong, I.M., Bridges, A.J., Newton, M.A., Shelef, M.A., 2019. Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis. Arthritis Rheumatol. art.41074.[3] Sirotti, S., Generali, E., Ceribelli, A., Isailovic, N., De Santis, M., Selmi, C., 2017. Personalized medicine in rheumatology: the paradigm of serum autoantibodies. Autoimmun. Highlights 8.Acknowledgments :The Department of Clinical Immunology at Rigshospitalet Copenhagen is acknowledged for providing the healthy donor blood. The study is part of the PROCIT study financed by the Danish Council for Independent Research (grant no. DFF - 7016-00233). Moreover, the Obelske Family Foundation, the Svend Andersen Foundation, the Spar Nord Foundation and the Danish National Mass Spectrometry Platform for Functional Proteomics (PRO-MS; grant no. 5072-00007B) are acknowledged for grants to the analytical platform are acknowledged for the funding to enabling parts of this study.Disclosure of Interests:Thomas B.G. Poulsen: None declared, Dres Damgaard: None declared, Malene Møller Jørgensen: None declared, Ladislav Senolt: None declared, Jonathan Blackburn Shareholder of: Sengenics Corporation, Consultant of: Director of Sengenics Corporation, Employee of: Director of Sengenics Corporation, Claus Henrik Nielsen: None declared, Allan Stensballe: None declared

scholarly journals POS0392 PRESENCE OF FOUR SERUM AUTOANTIBODIES ASSOCIATES WITH THE ACPA STATUS IN EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 425.3-426
Author(s):  
L. Lourido ◽  
C. Ruiz-Romero ◽  
L. Collado ◽  
M. Hansson ◽  
L. Klareskog ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Diagnosis ◽  
Specific Antigen ◽  
Coiled Coil ◽  
Population Based ◽  
Mitogen Activated Protein Kinase ◽  
Absolute Deviation ◽  
Swedish Population ◽  
Early Ra ◽  
Acpa Status

Background:The presence of anti-citrullinated protein antibodies (ACPAs) is a hallmark of rheumatoid arthritis (RA) that precede the development of the disease by years and is used for its clinical diagnosis. However, there are RA subjects that test negative for ACPA and thus the early diagnosis on these patients may be delayed. Furthermore, the presence or absence of ACPA in RA supports the hypothesis that on these two subsets of patients underlie different pathogenesis and clinical outcomes.Objectives:In this work, we searched for serum autoantibodies useful to assist the early diagnosis of ACPA-seronegative RA and its management.Methods:We profiled the serum autoantibody repertoire of 80 ACPA-seronegative and 80 ACPA-seropositive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort. A suspension bead array platform built on protein fragments within Human Protein Atlas and selected from an initial untargeted screening using arrays containing 2660 total antigens was employed to identify IgG and IgA serum autoantibodies. A validation phase on antigen suspension bead arrays was carried out on another set of samples from EIRA containing 386 ACPA-seropositive, 358 ACPA-seronegative and 372 randomly selected control subjects of the same age and sex. A sample-specific threshold based on 20 times the median absolute deviation plus the median of all signals was selected to determine the reactivity of samples. The Wilcoxon rank sum test and Fisher’s test were applied for the comparison of autoantibody levels and reactivity frequencies between the groups.Results:Our data revealed four antigens associated with the ACPA status (Table 1). Testis-specific Y-encoded-like protein 4 (TSPYL4) showed significantly higher IgG reactivity frequency in ACPA-seronegative subjects compared to ACPA-seropositive (8% vs. 3%; P<0.05). Significant differences at IgG autoantibody levels (P<0.05) were also observed between ACPA-seronegative subjects and controls for this specific antigen. Significantly higher IgG autoantibody levels (P<0.05) towards another antigen, dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6), were also observed in ACPA-seronegative subjects compared to ACPA-seropositive and controls. In contrast, we found significantly higher IgG autoantibody levels (P<0.05) in ACPA-seropositive individuals compared to ACPA-seronegative and controls towards two antigens, anosmin-1 (ANOS-1) and muscle related coiled-coil protein (MURC). ANOS-1 shows also significantly higher IgG reactivity frequency in ACPA-seropositive individuals compared to ACPA-seronegative and controls (22%, 9% and 6% respectively; P<0.05). Interestingly, three out of the four antigens discovered to be associated with the ACPA status in early RA are highly expressed in lungs and heart, two of the main extraarticular sites affected in RA. No significant differences were observed at IgA levels for any of the antigens analyzed.Table 1.Scheme of the different phases of the study, the features within each phase and the results. The reactivity to four antigens allows to distinguish ACPA-seronegative (ACPA-), ACPA seropositive (ACPA+) and controls.PhasesUntargeteddiscoveryTargeteddiscoveryTargetedvalidationNumber of samples80 ACPA-80 ACPA-358 ACPA-372 Controls80 ACPA+80 ACPA+386 ACPA+Antigen arrayplatformPlanararraysSuspensionbead array 1Suspensionbead array 2Number of antigens26606227Number of candidatebiomarkers6227 4 (TSPYL4,MAP2K6,ANOS1,MURC)Conclusion:Upon further validation in other early RA sample cohorts, our data suggest the measurement of these four autoantibodies may be useful for the early diagnosis of ACPA-seronegative RA and give insight into the pathogenesis of the different RA subsets.Characters from table content including title and footnotes:Disclosure of Interests:None declared

scholarly journals Association between interleukin-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Kewei Ren ◽  
Jilei Tang ◽  
Luming Nong ◽  
Nan Shen ◽  
Xiaolong Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Publication Bias ◽  
Genetic Model ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Pubmed Database ◽  
Dominant Genetic Model ◽  
Stratified Analysis ◽  
Acpa Status ◽  
Citrullinated Protein

Abstract Controversial results concerning the association between a polymorphism rs6822844 in the interleukin (IL) 21 (IL-21) gene and rheumatoid arthritis (RA) have existed. A meta-analysis to confirm above relationships is necessary to be performed immediately. We conducted a search in the PubMed database, covering all papers published up to 20 October 2018. Overall, six case–control studies with 3244 cases and 3431 healthy controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed with both Egger’s and Begg’s tests. After calculation, we found that IL-21 rs6822844 polymorphism could decrease RA risk in overall genetic models (allelic contrast: OR = 0.77, 95% CI = 0.62–0.97, P=0.024; TG versus GG: OR = 0.68, 95% CI = 0.50–0.92, P=0.013, and dominant genetic model: OR = 0.72, 95% CI = 0.55–0.94, P=0.016). Similarly, stratified analysis by race, source of control, significantly decreased association was found in Asians, Caucasians and hospital-based (HB) control source. Finally, in the subgroup analysis of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status, poorly decreased relationship was detected between IL-21 rs6822844 polymorphism and RF negative and ACPA positive RA risk, respectively. No obvious evidence of publication bias was detected in overall analysis. In summary, our study indicated that IL-21 rs6822844 polymorphism was significantly associated with decreased RA susceptibility.

Efficacy of three ELISA measurements of anti-cyclic citrullinated peptide antibodies in the early diagnosis of rheumatoid arthritis

2005 ◽  
Vol 43 (11) ◽  
Author(s):  
Antonio Fernández-Suárez ◽  
Sonsoles Reneses ◽  
Ingeborg Wichmann ◽  
Rita Criado ◽  
Antonio Núñez
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Diagnosis ◽  
High Specificity ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Cyclic Citrullinated Peptide ◽  
Citrullinated Peptide ◽  
Peptide Antibodies

AbstractThe objective of the present study was to determine the efficacy of anti-cyclic citrullinated peptide (anti-CCP) antibody detection in the early diagnosis of rheumatoid arthritis (RA), as well as to compare three commercially available enzyme-linked immunosorbent assay (ELISA) kits used to detect such antibodies. We analysed the presence of anti-CCP antibodies in the sera of 78 patients who had been newly referred from primary healthcare centres to the Early Polyarthritis Unit. We also included in the study a group of 50 healthy controls. None of the patients had previously received treatment for the disease. After 1-year follow-up, the diagnosis of RA was confirmed in 53 of these patients. The ELISA kits under study were IMMUNOSCAN RA (Euro-Diagnostica AB), QUANTA Lite™ CCP IgG ELISA (INOVA Diagnostic) and DIA-STAT™ Anti-CCP (Axis-Shield Diagnostics); the sensitivity obtained was 52.8%, 58.5% and 52.8%, respectively, with 100% specificity for all three kits. Anti-CCP antibodies detected the presence of RA in 26% of patients without positive rheumatoid factor (RF). The sum of anti-CCP antibodies or the presence of RF gave a sensitivity of up to 67%, with specificity ranging between 94 and 97%. Anti-CCP antibodies show high specificity for the diagnosis of RA. The three ELISAs analysed offer the same degree of diagnostic accuracy.

The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthritis

2010 ◽  
Vol 69 (6) ◽  
pp. 1110-1116 ◽  
Author(s):  
Diane van der Woude ◽  
Silje W Syversen ◽  
Ellen I H van der Voort ◽  
Kirsten N Verpoort ◽  
Guro L Goll ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Progression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prognostic Information ◽  
Radiographic Damage ◽  
The Relationship ◽  
Acpa Status ◽  
Citrullinated Protein

BackgroundThe presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated.ObjectiveTo investigate the relationship between ACPA isotypes, disease progression and radiological outcome.MethodsACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts.ResultsThe ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p<0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors.ConclusionsThe magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA.

scholarly journals AB0015 IDENTIFICATION OF KEY GENES TO SUPPORT SYSTEMIC LUPUS ERYTHEMATOSUS, RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS DIAGNOSIS BY TRANSCRIPTOMIC APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1311.2-1311
Author(s):  
A. Mashayekhi Sardoo ◽  
P. Leo ◽  
M. Santos ◽  
T. Costa ◽  
S. F. Almeida ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Early Diagnosis ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Inflammatory Rheumatic Diseases ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Early Therapy ◽  
Asas Criteria

Background:Early diagnosis of inflammatory rheumatic diseases (IRD), as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and axial Spondyloarthritis (axSpA) represents in our days a major clinical challenge. Increasing evidence has determined that early diagnosis, prompt treatment initiation and early achievement of remission are the best predictors of long-term clinical, functional and radiographic outcomes. Therefore, identification of sensitive biomarkers to support an early diagnosis to enable early therapy is of utmost importance [1,2].Objectives:This study aims to identify novel genes that may improve the current clinical diagnosis approach for early SLE, RA and axSpA.Methods:A cross-sectional study was conducted on 44 participants, 12 with axSpA (according to ASAS criteria), 11 with RA (according to ACR/EULAR criteria for RA), 10 with SLE (according to ACR classification criteria for SLE) and 11 Healthy Controls (HC), gender and age matched. Patients with co-occurrence of other IRD or having received biological therapies were excluded. Peripheral blood samples were collected into PAXgene tubes and stored in -80°C. mRNA profiling by RNA-seq was performed. Unpaired t-tests with multivariate permutation correction were applied to identify differentially expressed genes (DEGs) between patients and HC for each disease and within diseases. Enrichment analysis, Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analysis were also performed. DEGs that allow to distinguish each disease from HC and between diseases. The top DEGs (axSpA n=2, RA n=2, SLE n=3) identified were confirmed by quantitative RT-PCR.Results:For axSpA, genes involved in negative regulation of cytokines by JAK/STAT pathway and in osteoblast differentiation through STAT3 pathway, were confirmed. In SLE, genes involved in trap for immune complexes in peripheral blood and involved in nucleosome regulation, were also confirmed. Regarding RA, no genes were confirmed.Conclusion:Our work provides new insights into IRD pathogenesis, and discloses new biomarkers, which may be useful as either predictive biomarkers for diagnosis or therapeutic targets to improve IRD approach.Further validation are needed in different cohorts.References:[1]Monti, S. et al. (2015) ‘Rheumatoid arthritis treatment: The earlier the better to prevent joint damage’, RMD Open, 1(Suppl 1), pp. 1–5. doi: 10.1136/rmdopen-2015-000057.[2]Oglesby, A. et al. (2014) ‘Impact of early versus late systemic lupus erythematosus diagnosis on clinical and economic outcomes.’, Applied health economics and health policy, 12(2), pp. 179–90. doi: 10.1007/s40258-014-0085-x.Acknowledgments:To all patients and healthy controls who participated in the studyDisclosure of Interests:Atlas Mashayekhi Sardoo: None declared, Paul Leo: None declared, Mariana Santos: None declared, Tiago Costa: None declared, Sergio Fernandes Almeida: None declared, Sara Maia: None declared, Vladimir Benes: None declared, Mattew Brown Speakers bureau: MSD, Pfizer, Novartis, Jaime Branco Speakers bureau: Vitoria, Fernando Pimentel dos Santos Speakers bureau: Novartis, Pfizer, Biogen, Vitoria,

scholarly journals Salivary citrullinated proteins in rheumatoid arthritis and associated periodontal disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ildikó Tar ◽  
Éva Csősz ◽  
Edit Végh ◽  
Karin Lundberg ◽  
Nastya Kharlamova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Periodontal Disease ◽  
Control Group ◽  
Healthy Controls ◽  
Periodontal Status ◽  
Protein Levels ◽  
Reduced Height ◽  
Significant Difference ◽  
Citrullinated Proteins ◽  
Citrullinated Protein

AbstractPeriodontal disease (PD) can be an important precipitating factor in the production of citrullinated proteins. Its importance is emphasized, but it is not the only way to produce citrullinated proteins. The aim of the current study was to determine the periodontal conditions and the salivary citrullinated protein content in patients with rheumatoid arthritis (RA) compared to healthy controls. We also wished to correlate citrullinated protein levels in the saliva and serum biomarkers with the periodontal status and temporomandibular joint (TMJ) involvement of patients with RA. Twenty-three patients with RA and 17 healthy controls participated the study. Saliva samples were taken: citrulline content of saliva was measured. Blood test results for patients with RA were collected. TMJ disorders were described. Cariological and periodontal indices were registered. Periodontal conditions and periodontal staging were also registered. Comparison of measured values between groups was performed. Intragroup correlation of patients’ values was counted. The prevalence of TMJ complaints was significantly higher in the RA group (8/23) versus controls (1/17). The patients with RA had worse periodontal condition because more patients with RA had gingivitis with a significantly higher bleeding on probing (BOP) (RA: 22.4 ± 25.0%; controls: 6.36 ± 11.6%; p = 0.018). Gingival index (GI) was also significantly higher in the patients than in controls (RA: 0.68 ± 0.58; controls: 0.19 ± 0.38; p = 0.010). The citrullinated protein (relative) content of saliva did not differ significantly (p = 0.147) between patients with RA (1102.2 ± 530.8) and healthy controls (1873.1 ± 1594.9). In RA, the salivary anti-CCP levels positively correlated with PD staging (R = 0.464, p = 0.039) . Control subjects more commonly had healthy gingiva than RA patients. Moreover, in the control group more individuals had intact and reduced height periodontium than periodontitis compared to the RA group. There was no significant difference in the levels of salivary citrulline between patients with RA and controls, despite the significant differences in their periodontal status. Thus, salivary citrulline levels are not associated with RA disease severity.

scholarly journals POS0395 ANTI-ACETYLATED PROTEIN ANTIBODIES IN RHEUMATOID ARTHRITIS (RA): CLUES FOR THE STARTING POINT OF AUTOANTIBODY RESPONSES IN RA

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 426.3-427
Author(s):  
T. J. van Wesemael ◽  
A. L. Dorjée ◽  
T. Huizinga ◽  
A. van der Helm - van Mil ◽  
R. Toes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Controls ◽  
Serum Samples ◽  
Baseline Serum ◽  
Control Peptide ◽  
Autoantibody Response ◽  
Starting Point ◽  
Early Inflammatory Arthritis ◽  
And Control ◽  
Citrullinated Protein

Background:Rheumatoid arthritis (RA) is characterized by autoantibodies such as rheumatoid factor (RF) and anti-modified protein autoantibodies (AMPAs) like anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein antibodies (anti-CarP). Recently, another AMPA: anti-acetylated protein antibodies (AAPA) have been found in RA patients [1]. The prevalence of AAPA antibodies and their isotypes have yet to be determined. Since isotype profiles reflect the breadth of an immune response, the prevalence of AAPA isotypes in arthritis patients with and without RA can help to understand the relevance of this autoantibody response in RA.Objectives:To describe the prevalence of AAPA isotypes in arthritis patients with and without RA.Methods:In 650 RA patients fulfilling the 1987 RA criteria and 555 non-RA arthritis patients from the Leiden Early Arthritis Cohort, baseline serum samples were screened by ELISA for IgG, IgM and IgA to an acetylated- and control peptide that was based upon the CCP-2 backbone. The cutoff for positivity was based on 80 controls (mean + 2SD). A sample was considered positive if it was above the cutoff and was 0.1 optical density higher on the acetylated peptide than on the control peptide.Results:AAPA IgG was found in 36% of RA patients versus 6.7% of non-RA arthritis patients (figure 1a). Within RA patients, AAPA IgG antibodies were mostly present in the ACPA-(CCP-2) positive group (64% in ACPA-positive, compared to 5% in ACPA-negative). Levels of AAPA IgG and IgA were higher in RA patients than in healthy controls and non-RA arthritis patients (figure 1b), however, surprisingly, no difference in levels was found for IgM.When isotype profiles in AAPA- positive arthritis patients were compared, patients with RA were more often positive for two or more isotypes then patients without RA, and thus displayed considerably more overlap in AAPA isotypes compared to non-RA patients (table 1). Intriguingly, IgM AAPA was the most prevalent isotype in non-RA patients, versus IgG in RA patients.Table 1.Anti-acetylated protein antibody (AAPA) isotype overlap in AAPA positive patients.AAPA isotypeRA patients (=310) n (%)Non-RA arthritis patients (n=106) n (%)IgG+IgM-IgA-115 (37.1)28 (5.1)IgG-IgM+IgA-52 (16.8)48 (8.7)IgG-IgM-IgA+14 (4.5)13 (2.3)IgG+IgM+IgA-24 (7.7)3 (0.5)IgG+IgM-IgA+37 (11.9)4 (0.7)IgG-IgM+IgA+9 (2.9)8 (1.4)IgG+IgM+IgA+59 (19.0)2 (0.4)AAPA: anti-acetylated protein antibodies, RA: rheumatoid arthritisConclusion:AAPA are detected in one third of RA patients, and mainly in the ACPA-positive subgroup. The predominance of IgM AAPA in non-RA arthritis patients and healthy controls suggests that healthy persons can develop AAPA IgM without the development of RA. These results also suggest that in healthy individuals, AAPA responses can occur, but do not mature past the IgM-stage, while in RA patients, the AAPA-response does mature and might form a “starting point” for development of other AMPA leading to the concurrent present of several AMPA in disease.References:[1]Juarez, M., et al., Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis. Ann Rheum Dis, 2016. 75(6): p. 1099-107.Disclosure of Interests:None declared

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