Anti-Citrullinated Protein Antibodies in Unaffected First-Degree Relatives of Rheumatoid Arthritis Patients

2013 ◽  
Vol 65 (6) ◽  
pp. 1439-1447 ◽  
Author(s):  
Lillian Barra ◽  
Mathias Scinocca ◽  
Sheri Saunders ◽  
Rajesh Bhayana ◽  
Sherry Rohekar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
First Degree Relatives ◽  
Citrullinated Protein

scholarly journals Association of Antibodies to Citrullinated Protein Antigens with Blood Pressure in First-Degree Relatives of Rheumatoid Arthritis Patients: The Studies of the Etiology of Rheumatoid Arthritis

2017 ◽  
Vol 46 (6) ◽  
pp. 481-487 ◽  
Author(s):  
Jan M. Hughes-Austin ◽  
Ryan W. Gan ◽  
Kevin D. Deane ◽  
Michael H. Weisman ◽  
M. Kristen Demoruelle ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Pressure ◽  
High Sensitivity ◽  
Cross Sectional Study ◽  
Analysis Of Covariance ◽  
Protein Antigens ◽  
Cross Sectional ◽  
Reactive Protein ◽  
First Degree Relatives ◽  
Citrullinated Protein

Background: Hypertension is more common in patients with rheumatoid arthritis (RA) than in the general population. It is unknown whether hypertension is due to RA-related medications or the disease itself. Therefore, we sought to investigate associations between RA-related autoantibodies, specifically antibodies to citrullinated protein antigens (ACPA) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in first-degree relatives of RA patients, who were free of RA and RA-related medications. We hypothesized that a greater number of detectable ACPA would be associated with high SBP and DBP, independent of other risk factors in these first-degree relatives. Methods: We evaluated associations between ACPA and SBP and DBP in a cross-sectional study of 72 first-degree relatives (defined as parent, child, or sibling) of RA patients. Fifteen ACPA were measured using a Bio-Plex bead-based assay; each was dichotomized as positive/negative based on pre-specified cut-points. Analysis of covariance was used to evaluate associations between ACPA positivity and SBP and DBP, adjusting for age, sex, race, body mass index (BMI), pack-years of smoking, high sensitivity C-reactive protein (hsCRP), and current use of anti-hypertensive medications. Results: Average age was 51 and 69% were women. Mean SBP was 119 ± 18 and DBP was 74 ± 9 mm Hg. Thirty-three (46%) first-degree relatives were positive for ≥1 ACPA; and were younger, had lower BMI, more pack-years of smoking, and higher hsCRP concentrations compared to ACPA negative first-degree relatives. For each additional positive ACPA, SBP was 0.98 ± 0.5 mm Hg (p = 0.05) higher, and DBP was 0.66 ± 0.3 mm Hg (p = 0.04) higher. Anti-cit-fibrinogen A (211–230) positive and anti-cit-filaggrin positive first-degree relatives had 11.5 and 13.9 mm Hg higher SBP (p = 0.02) respectively. Anti-cit-clusterin, cit-filaggrin, and cit-vimentin positive first-degree relatives had 7–8 mm Hg higher DBP (p = 0.03, 0.05, 0.05 respectively), compared to being negative for these individual ACPA. Consistent with associations between ACPA, SBP, and DBP, anti-cyclic citrullinated peptides (anti-CCP2) positive first-degree relatives had 16.4± (p = 0.03) higher SBP and 12.1± mm Hg (p = 0.01) higher DBP than anti-CCP2 negative first-degree relatives. Conclusion: In first-degree relatives without RA, ACPA positivity is associated with higher SBP and DBP. Subclinical autoimmune processes and ACPA may play a role in the vascular changes potentially leading to hypertension prior to RA onset.

scholarly journals POS0441 DEVELOPMENT OF RHEUMATOID ARTHRITIS AMONG ANTI-CITRULLINATED PROTEIN ANTIBODIES POSITIVE ASYMPTOMATIC INDIVIDUALS: A PROSPECTIVE OBSERVATIONAL STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 449.1-449
Author(s):  
S. Mizuki ◽  
K. Horie ◽  
K. Imabayashi ◽  
K. Mishima ◽  
K. Oryoji
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Observational Study ◽  
Rheumatoid Factor ◽  
Prospective Observational Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
P Value ◽  
Healthy Population ◽  
Asymptomatic Individuals ◽  
Citrullinated Protein

Background:In the idividuals with genetic and enviromental risk factors, immune events at mucosal surfaces occur and may precede systemic autoimmunity. Anti-citrullinated protein antibodies (ACPA) are present in the serum for an average of 3-5 years prior to the onset of rheumatoid arthritis (RA) during an asymptomatic period. In ACPA-positivite individuals, the additional presence of RA-related risk factors appears to add significant power for the development of RA. To date, there have been few reports in which clinical courses of ACPA-positive asymptomatic individuals were investigated prospectively.Objectives:To observe the clinical time course of ACPA-positive healthy population for the development of RA.Methods:Healthy volunteers without joint pain or stiffness, who attended the comprehensive health screening of our hospital, were enrolled in this prospective observational study. The serum ACPA levels were quantified by Ig-G anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay with levels > 4.4 U/mL considered positive. ACPA-positive subjects were followed by rheumatologists of our department clinically or a questionnaire sent by mail for screening to detect arthritis.Results:5,971 healthy individuals without joint symptons were included. Ninty-two (1.5%) were positive for ACPA. Of these, 19 (20.7%) developed RA and two were suspected as RA by mail questionnaire. Their average age were 58-years, and women were 68%. The average duration between the date of serum sampling and diagnosis was 10.7 months. ACPA-positive individuals who developed to RA had higher serum ACPA and Ig-M rheumatoid factor levels than ACPA-positive individuals who did not (P value by Mann-Whitney U test: 0.002, 0.005, respectively).Conclusion:Among ACPA-positive asymptomatic individuals, 20% developed RA. The higher titer of ACPA and Ig-M rheumatoid factor levels are risk factors for devoloping RA.Disclosure of Interests:None declared

ASSOCIATIONS BETWEEN SERUM ANTIBODIES TO PERIODONTAL PATHOGENS AND PRECLINICAL PHASES OF RHEUMATOID ARTHRITIS

Rheumatology ◽  
2021 ◽  
Author(s):  
Daniel Manoil ◽  
Delphine S Courvoisier ◽  
Benoit Gilbert ◽  
Burkhard Möller ◽  
Ulrich A Walker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Primary Outcome ◽  
Signs And Symptoms ◽  
Serum Levels ◽  
Study Cohort ◽  
Periodontal Pathogens ◽  
Serum Antibodies ◽  
Current Smoking ◽  
Clinical Arthritis ◽  
Citrullinated Protein

Abstract Objectives To examine whether serum antibodies against selected periodontal pathogens are associated with early symptoms of rheumatoid arthritis (RA) development in healthy individuals at risk of developing the disease. Methods Within an ongoing study cohort of first-degree relatives of patients with RA (RA-FDRs), we selected four groups corresponding to specific preclinical phases of RA development (n = 201). (1) RA-FDR controls without signs and symptoms of arthritis nor RA-related autoimmunity (n = 51); (2) RA-FDRs with RA-related autoimmunity (n = 51); (3) RA-FDRs with inflammatory arthralgias without clinical arthritis (n = 51); (4) RA-FDRs who have presented at least one swollen joint (“unclassified arthritis”) (n = 48). Groups were matched for smoking, age, sex and shared epitope status. The primary outcome was IgG serum levels against five selected periodontal pathogens and one commensal oral species assessed using validated-in-house ELISA assays. Associations between IgG measurements and preclinical phases of RA development were examined using Kruskal-Wallis or Mann-Whitney tests (α = 0.05). Results None of the IgGs directed against individual periodontal pathogens significantly differed between the four groups of RA-FDRs. Further analyses of cumulated IgG levels into bacterial clusters representative of periodontal infections, revealed significantly higher IgG titers against periodontopathogens in anti-citrullinated protein antibodies (ACPA)-positive RA-FDRs (p = 0.015). Current smoking displayed a marked trend towards reduced IgG titers against periodontopathogens. Conclusion Our results do not suggest an association between serum IgG titers against individual periodontal pathogens and specific preclinical phases of RA development. However, associations between cumulative IgG titers against periodontopathogens and the presence of ACPAs suggest a synergistic contribution of periodontopathogens to ACPA development.

scholarly journals POS0460 ASSOCIATION OF ANTI-CITRULLINATED PROTEIN ANTIBODIES OF IgA SUBCLASSES WITH SUSTAINED REMISSION AND FLARE IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 461-461
Author(s):  
M. V. Sokolova ◽  
J. Rech ◽  
M. Hagen ◽  
G. Schett ◽  
U. Steffen (née Harre)
Keyword(s):  
Rheumatoid Arthritis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sustained Remission ◽  
Das28 Score ◽  
Effector Functions ◽  
Conventional Dmards ◽  
The Impact ◽  
Citrullinated Protein ◽  
Iga Subclasses ◽  
Over Time

Background:Understanding key mechanisms of flare development and sustained remission is one of the acute goals in modern rheumatology. Anti-citrullinated protein antibodies (ACPA) are the most abundant and specific autoantibodies in rheumatoid arthritis (RA) patients. However, the impact of ACPA of IgA isotype is poorly defined. IgA ACPA were previously shown to have a higher percentage of IgA2 in comparison to total IgA; and a correlation between IgA2% ACPA with the DAS28 score was observed in a previous study [1]. Of note, IgA1 and IgA2 were shown to exhibit different effector functions, with IgA2 being pro-inflammatory, which might be the background for its role in RA [1].Objectives:We aimed to investigate, whether IgA ACPA could be used as a predictive factor for flare development in RA; and to look further into the changes in IgA ACPA levels in patients remaining in stable remission versus patients developing flare.Methods:We analysed serum of 111 patients from a multicentre randomized controlled trial ‘RETRO’. The study observational period was 12 months. Patients in the trial had to be in stable remission (DAS28-ESR<2.6) for a minimum of 6 months and were randomized into 3 different treatment arms: continuation of treatment, tapering by 50% or a gradual tapering until discontinuation [2]. IgA ACPA concentrations were measured with an enzyme-linked immunosorbent assay on CCP2-pre-coated plates.Results:60% of patients had IgG-ACPA. IgA ACPA levels were higher among the IgG-ACPA-positive patients (median 4.7 versus 2.24 µg/ml, p<0.0001). Baseline IgA1 and 2 ACPA levels were not different between patients who had a flare later on in the study period and those remaining in remission, showing no predictive value for flare development. However, the percentage of IgA2 in ACPA was correlating with the first registered DAS28 after flare (r=0.36, p=0.046). After the 12 months study period, IgA2 ACPA as well as IgA2% ACPA decreased significantly in patients who remained in stable remission by 17.5% (median, p<0.0001) and 13.6% (p=0.0006), respectively. By contrast, there was no significant change in IgA2 ACPA levels over time in patients who developed a flare. IgA1 ACPA levels remained stable over time. Disease management strategies did not seem to influence IgA ACPA levels in a specific way, as baseline levels were similar between patients on biological and conventional DMARDs and changes in levels after 12 months did not depend on the assignment to either of the study arms.Conclusion:Neither IgA1 nor IgA2 ACPA levels were predictive of flare development or associated with treatment strategies (though rituximab, JAK-inhibitors and abatacept were not amongst treatment options). However, in patients remaining in sustained remission after 1 year a decrease in IgA2 and IgA2% ACPA was observed and IgA2% ACPA was associated with DAS28 score registered after flare. This could be an indication towards ACPA of IgA2 isotype contributing to the severity of flare, alongside other factors, and its reduction being associated with a prolonged state of remission.References:[1]Steffen U, Koeleman CA, Sokolova MV, et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun 11, 120 (2020).[2]Haschka J, Englbrecht M, Hueber AJ, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 75:45-51 (2016).Disclosure of Interests:None declared

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