scholarly journals Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation

2021 ◽  
Vol 22 (19) ◽  
pp. 10576
Author(s):  
Eui-Jong Kwon ◽  
Ji Hyeon Ju
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Death ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Diagnosis And Prognosis ◽  
Immunologic Factors ◽  
Microbial Infections ◽  
Cell Death Mechanisms ◽  
Citrullinated Protein ◽  
Peptide Antibodies

Rheumatoid arthritis (RA) is caused by prolonged periodic interactions between genetic, environmental, and immunologic factors. Posttranslational modifications (PTMs) such as citrullination, carbamylation, and acetylation are correlated with the pathogenesis of RA. PTM and cell death mechanisms such as apoptosis, autophagy, NETosis, leukotoxic hypercitrullination (LTH), and necrosis are related to each other and induce autoantigenicity. Certain microbial infections, such as those caused by Porphyromonasgingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri, can induce autoantigens in RA. Anti-modified protein antibodies (AMPA) containing anti-citrullinated protein/peptide antibodies (ACPAs), anti-carbamylated protein (anti-CarP) antibodies, and anti-acetylated protein antibodies (AAPAs) play a role in pathogenesis as well as in prediction, diagnosis, and prognosis. Interestingly, smoking is correlated with both PTMs and AMPAs in the development of RA. However, there is lack of evidence that smoking induces the generation of AMPAs.

scholarly journals AB0179 INFLUENCE OF AINFLUENCE OF ANTI-CITRULLINATED PROTEIN/PEPTIDE ANTIBODIES (ACPAS)ON ARTICULAR MANIFESTATIONS, DISEASE ACTIVITY AND STRUCTURAL SEVERITY IN ALGERIAN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1115.1-1115
Author(s):  
F. Rahal ◽  
N. Brahumi ◽  
A. Ladjouze-Rezig ◽  
S. Lefkir
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Activity Score ◽  
Symptom Duration ◽  
Early Ra ◽  
The Mean ◽  
Citrullinated Protein ◽  
Peptide Antibodies

Background:Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). There are also suggested to have a more severe rheumatoid arthritis.Objectives:The aim of this study was to assess the influence of ACPA on disease activity, radiological severity, and functional disability in Algerian patient with early rheumatoid arthritis (RA).Methods:Consecutive early RA patients (symptom duration ≤24 months) recruited were included in the descriptive, longitudinal, prospective study. Demographic, biological, immunological and radiographic data were collected at the time of inclusion in the study. Disease activity as determined by the Disease Activity Score 28-CPR (DAS28- CPR: 4 variables), functional handicap as calculated by Heath Assessment Score (HAQ), and bone and joint damage as evaluated by Sharp-Van der Heijde (SVDH) erosion and narrowing score.Results:One hundred and sixty-one patients with RA were recruited. Patients mean age 43.71±14 years and mean symptom duration at inclusion was 10.48±7 months. Small and larges were affected in 64,3%. The mean ESR was 23,53±15,2 mm/1st hour, and the mean CRP level was 19,42±39.8 mg/l. Rheumatoid Factors (RFs) and Anti-Citrullinated Protein Antibodies (ACPAs) were present in 74% and 88% of patients, respectively. The presence of ACPAs was significantly associated with DAS28 (p=0,004) and HAQ (p=0,002). There was no significant difference in inflammatory markers and radiographic SVDH score between patients with and without ACPAs. Stepwise regression analysis showed that the presence of ACPAs was independently associated with localization when RA affected smalls and larges joint in the same time (OR=5,24; IC 95% 1,224-22,483; p=0,026).Conclusion:These data show that in patients with early RA, ACPAs positivity was significantly associated with articular manifestations, activity disease and functional handicap, but not with structural damage.References:[1]Nikiphorou E, Norton S, Young A, et al. Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds. Ann Rheum Dis. 2016;75(12):2080-2086. doi:10.1136/annrheumdis-2015-208669.[2]Karimifar M, Salesi M, Farajzadegan Z. The association of anti-CCP1 antibodies with disease activity score 28 (DAS-28) in rheumatoid arthritis. Adv Biomed Res. 2012;1:30. doi:10.4103/2277-9175.98156.[3]Boman A, Brink M, Lundquist A, et al. Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study. RMD Open. 2019;5(2):e000946. Published 2019 Sep 3. doi:10.1136/rmdopen-2019-000946.Disclosure of Interests:None declared

scholarly journals From Rheumatoid Factor to Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies for Diagnosis and Prognosis Prediction in Patients with Rheumatoid Arthritis

2021 ◽  
Vol 22 (2) ◽  
pp. 686
Author(s):  
Chao-Yi Wu ◽  
Huang-Yu Yang ◽  
Shue-Fen Luo ◽  
Jenn-Haung Lai
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Response To Therapy ◽  
Current Evidence ◽  
Prognosis Prediction ◽  
Diagnosis And Prognosis ◽  
Systemic Inflammatory Disease ◽  
Citrullinated Protein

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease mainly involving synovial inflammation and articular bone destruction. RA is a heterogeneous disease with diverse clinical presentations, prognoses and therapeutic responses. Following the first discovery of rheumatoid factors (RFs) 80 years ago, the identification of both anti-citrullinated protein antibodies (ACPAs) and anti-carbamylated protein antibodies (anti-CarP Abs) has greatly facilitated approaches toward RA, especially in the fields of early diagnosis and prognosis prediction of the disease. Although these antibodies share many common features and can function synergistically to promote disease progression, they differ mechanistically and have unique clinical relevance. Specifically, these three RA associating auto-antibodies (autoAbs) all precede the development of RA by years. However, while the current evidence suggests a synergic effect of RF and ACPA in predicting the development of RA and an erosive phenotype, controversies exist regarding the additive value of anti-CarP Abs. In the present review, we critically summarize the characteristics of these autoantibodies and focus on their distinct clinical applications in the early identification, clinical manifestations and prognosis prediction of RA. With the advancement of treatment options in the era of biologics, we also discuss the relevance of these autoantibodies in association with RA patient response to therapy.

scholarly journals Technical and Diagnostic Performance of 6 Assays for the Measurement of Citrullinated Protein/Peptide Antibodies in the Diagnosis of Rheumatoid Arthritis

2007 ◽  
Vol 53 (3) ◽  
pp. 498-504 ◽  
Author(s):  
Dries Coenen ◽  
Patrick Verschueren ◽  
René Westhovens ◽  
Xavier Bossuyt
Keyword(s):  
Rheumatoid Arthritis ◽  
Diagnostic Accuracy ◽  
Diagnostic Performance ◽  
Connective Tissue Diseases ◽  
Antigen Specificity ◽  
Serum Samples ◽  
Technical Performance ◽  
Two Samples ◽  
Citrullinated Protein ◽  
Peptide Antibodies

Abstract Background: Several anticitrullinated protein/peptide antibodies (ACPA) assays have been reported to be of diagnostic value for rheumatoid arthritis (RA). We evaluated the technical performance and diagnostic accuracy of 6 ELISAs for the detection of antibodies to citrullinated protein/peptide antigens. Methods: ACPA were determined in 298 serum samples using 6 commercially available ACPA assays. One hundred two samples were from RA patients, including patients with early and established RA, and 196 were from controls, including patients with psoriatic arthritis, connective tissue diseases, organ-specific autoimmune diseases, and a group of consecutive patients for whom a rheumatologist ordered anticyclic citrullinated peptide (CCP) antibodies. The ELISA reagent sets under study were Citrullinated Protein Antibodies (Genesis), Anti-MCV (Orgentec), Immunoscan RA (Euro-Diagnostica), Anti-CCP IgG ELISA (Euroimmun), EliA™ CCP (Phadia), and Quanta Lite™ CCP3 IgG ELISA (Inova). Technical performance (imprecision, linearity, correlation, and agreement) and diagnostic accuracy (sensitivity and specificity) were compared. Results: Variable technical performance was noted among the different ACPA assays, with some assays displaying poor reproducibility and bad linearity. ACPA results were well correlated among assays with the same antigen specificity, but the numerical values reported for each assay differed widely. Using cutoff values proposed by the manufacturer, diagnostic sensitivities ranged between 69.6% and 77.5% and specificities between 87.8% and 96.4%. The areas under the ROC curves were comparable among the different assays. Conclusions: Overall diagnostic performance of ACPA assays is comparable among the different assays, but standardization is needed. For some assays, analytical characteristics could be improved.

scholarly journals Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens

2015 ◽  
Vol 17 (1) ◽  
Author(s):  
Cátia Fernandes-Cerqueira ◽  
Elena Ossipova ◽  
Sunithi Gunasekera ◽  
Monika Hansson ◽  
Linda Mathsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Citrullinated Protein ◽  
Peptide Antibodies

scholarly journals Relatives Without Rheumatoid Arthritis Show Reactivity to Anti-Citrullinated Protein/Peptide Antibodies That Are Associated With Arthritis-Related Traits: Studies of the Etiology of Rheumatoid Arthritis

2013 ◽  
Vol 65 (8) ◽  
pp. 1995-2004 ◽  
Author(s):  
Kendra A. Young ◽  
Kevin D. Deane ◽  
Lezlie A. Derber ◽  
Jan M. Hughes-Austin ◽  
Catriona A. Wagner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Citrullinated Protein ◽  
Peptide Antibodies

Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: Specificity and relation with rheumatoid factor

2005 ◽  
Vol 4 (7) ◽  
pp. 468-474 ◽  
Author(s):  
B. Vander Cruyssen ◽  
I. Peene ◽  
T. Cantaert ◽  
I.E.A. Hoffman ◽  
L. De Rycke ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Citrullinated Protein ◽  
Peptide Antibodies

scholarly journals Post-translational control of RIPK3 and MLKL mediated necroptotic cell death

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1297 ◽  
Author(s):  
James M. Murphy ◽  
James E. Vince
Keyword(s):  
Cell Death ◽  
Translational Control ◽  
Kinase Domain ◽  
Current Evidence ◽  
Deubiquitinating Enzymes ◽  
Critical Function ◽  
Interacting Protein ◽  
Mixed Lineage Kinase ◽  
Microbial Infections ◽  
Cell Death Mechanisms

Several programmed lytic and necrotic-like cell death mechanisms have now been uncovered, including the recently described receptor interacting protein kinase-3 (RIPK3)-mixed lineage kinase domain-like (MLKL)-dependent necroptosis pathway. Genetic experiments have shown that programmed necrosis, including necroptosis, can play a pivotal role in regulating host-resistance against microbial infections. Alternatively, excess or unwarranted necroptosis may be pathological in autoimmune and autoinflammatory diseases. This review highlights the recent advances in our understanding of the post-translational control of RIPK3-MLKL necroptotic signaling. We discuss the critical function of phosphorylation in the execution of necroptosis, and highlight the emerging regulatory roles for several ubiquitin ligases and deubiquitinating enzymes. Finally, based on current evidence, we discuss the potential mechanisms by which the essential, and possibly terminal, necroptotic effector, MLKL, triggers the disruption of cellular membranes to cause cell lysis.

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