scholarly journals Specificity of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 37 ◽  
Author(s):  
Nicole H. Trier ◽  
Bettina E. Holm ◽  
Paul R. Hansen ◽  
Ole Slot ◽  
Henning Locht ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Amino Acids ◽  
Autoimmune Disease ◽  
Unknown Etiology ◽  
Specific Nature ◽  
Citrullinated Protein ◽  
Disease Specific

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. The majority of individuals with RA are positive for the disease-specific anti-citrullinated protein antibodies (ACPAs). These antibodies are primarily of cross-reactive nature, hence, the true autoantigen to ACPA remains unidentified. In this study, we analyzed the reactivity of RA sera to several post-translationally modified epitopes, in order to further characterize the specific nature of ACPAs by immunoassays. Substituting citrulline with other amino acids, e.g., D-citrulline, homo-citrulline and methyl-arginine illustrated that ACPAs are utmost specific for citrullinated targets. Collectively, these findings support that ACPAs and citrullinated targets are specific for RA, making citrulline-containing peptide targets the most effective assays for detection of ACPAs.

scholarly journals Individuals at risk for developing rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential

2021 ◽  
Author(s):  
Mihnea R. Mangalea ◽  
David Paez-Espino ◽  
Kristopher Kieft ◽  
Anushila Chatterjee ◽  
Jennifer A. Seifert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
At Risk ◽  
Autoimmune Disease ◽  
Intestinal Microbiota ◽  
Disease Development ◽  
Metabolic Potential ◽  
Metabolic Genes ◽  
Auxiliary Metabolic Genes ◽  
Citrullinated Protein ◽  
Insight Into

SUMMARYRheumatoid arthritis (RA) is an autoimmune disease characterized in seropositive individuals by the presence of anti-cyclic citrullinated protein (CCP) antibodies. RA is linked to the intestinal microbiota, yet the association of microbes with CCP serology and their contribution to RA is unclear. We describe intestinal phage communities of individuals at risk for developing RA, with or without anti-CCP antibodies, whose first degree relatives have been diagnosed with RA. We show that at-risk individuals harbor intestinal phage compositions that diverge based on CCP serology, are dominated by Lachnospiraceae phages, and originate from disparate ecosystems. These phages encode unique repertoires of auxiliary metabolic genes (AMGs) which associate with anti-CCP status, suggesting that these phages directly influence the metabolic and immunomodulatory capability of the microbiota. This work sets the stage for the use of phages as preclinical biomarkers and provides insight into a possible microbial-based causation of RA disease development.

Reconstruction and analysis of the lncRNA–miRNA–mRNA network based on competitive endogenous RNA reveal functional lncRNAs in rheumatoid arthritis

2017 ◽  
Vol 13 (6) ◽  
pp. 1182-1192 ◽  
Author(s):  
Hui Jiang ◽  
Rong Ma ◽  
Shubiao Zou ◽  
Yongzhong Wang ◽  
Zhuqing Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
General Population ◽  
Unknown Etiology ◽  
Competitive Endogenous Rna

Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology, occurring in approximately 1.0% of general population.

scholarly journals IgA subclasses have different effector functions associated with distinct glycosylation profiles

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ulrike Steffen ◽  
Carolien A. Koeleman ◽  
Maria V. Sokolova ◽  
Holger Bang ◽  
Arnd Kleyer ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Sialic Acid ◽  
Autoimmune Disease ◽  
Disease Activity ◽  
Immune Cells ◽  
Immunoglobulin A ◽  
Effector Functions ◽  
Serum Iga ◽  
Iga Subclasses ◽  
Disease Specific

AbstractMonomeric serum immunoglobulin A (IgA) can contribute to the development of various autoimmune diseases, but the regulation of serum IgA effector functions is not well defined. Here, we show that the two IgA subclasses (IgA1 and IgA2) differ in their effect on immune cells due to distinct binding and signaling properties. Whereas IgA2 acts pro-inflammatory on neutrophils and macrophages, IgA1 does not have pronounced effects. Moreover, IgA1 and IgA2 have different glycosylation profiles, with IgA1 possessing more sialic acid than IgA2. Removal of sialic acid increases the pro-inflammatory capacity of IgA1, making it comparable to IgA2. Of note, disease-specific autoantibodies in patients with rheumatoid arthritis display a shift toward the pro-inflammatory IgA2 subclass, which is associated with higher disease activity. Taken together, these data demonstrate that IgA effector functions depend on subclass and glycosylation, and that disturbances in subclass balance are associated with autoimmune disease.

scholarly journals Rheumatoid Arthritis-Associated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans

2019 ◽  
Vol 8 (9) ◽  
pp. 1309 ◽  
Author(s):  
Eduardo Gómez-Bañuelos ◽  
Amarshi Mukherjee ◽  
Erika Darrah ◽  
Felipe Andrade
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Porphyromonas Gingivalis ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Unknown Etiology ◽  
Preventive Interventions ◽  
Periodontal Pathogens ◽  
Periodontal Bacteria ◽  
Immune Mediated

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by immune-mediated damage of synovial joints and antibodies to citrullinated antigens. Periodontal disease, a bacterial-induced inflammatory disease of the periodontium, is commonly observed in RA and has implicated periodontal pathogens as potential triggers of the disease. In particular, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans have gained interest as microbial candidates involved in RA pathogenesis by inducing the production of citrullinated antigens. Here, we will discuss the clinical and mechanistic evidence surrounding the role of these periodontal bacteria in RA pathogenesis, which highlights a key area for the treatment and preventive interventions in RA.

Novel Nano Carriers for the Treatment of Progressive Auto Immune Disease Rheumatoid Arthritis

2020 ◽  
Vol 26 ◽  
Author(s):  
Ritu Mishra ◽  
Swati Gupta
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Autoimmune Disease ◽  
Drug Delivery Systems ◽  
Clinical Manifestations ◽  
Adaptive Immune Response ◽  
Delivery Systems ◽  
Current Therapy ◽  
Genetic And Environmental Factors ◽  
Novel Drug

Background: Rheumatoid arthritis (RA) is the most common occurring progressive, autoimmune disease, affecting 1% of the population and the ratio of affected women is three times as compared to men in most developing countries. Clinical manifestations of RA are the presence of anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) in blood, tendered joints and soreness of the muscles. Some other factors which may lead to chronic inflammation are genetic and environmental factors as well as adaptive immune response. Several conventional drugs are available for the treatment of RA but have their own drawbacks which can be overcome by the use of novel drug delivery systems. : The objective of the present review is to focus on the molecular pathogenesis of the disease and its current conventional treatment with special reference to the role of novel drug delivery systems encapsulating anti rheumatic drugs and herbal drugs in passive and receptor mediated active targeting against RA. On reviewing the conventional and current therapeutics agains RA, we conclude that, although the current therapy for the treatment of RA is capable enough, yet more advances in the field of targeted drug delivery will sanguinely result in effective and appropriate treatment of this autoimmune disease.

Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

2019 ◽  
Vol 15 (4) ◽  
pp. 316-320
Author(s):  
Mir Amir Aghdashi ◽  
Seyedmostafa Seyedmardani ◽  
Sholeh Ghasemi ◽  
Zohre Khodamoradi
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Arthritis ◽  
Unknown Etiology ◽  
Tender Joint Count ◽  
Serum Samples ◽  
Tender Joint ◽  
Cross Sectional ◽  
Calprotectin Level ◽  
Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

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.

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