Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

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Predictive role of ultrasound remission for progressive ultrasonography-detected structural damage in patients with rheumatoid arthritis

Journal of Investigative Medicine ◽

10.1136/jim-2021-001885 ◽

2021 ◽

pp. jim-2021-001885

Author(s):

Feifei Liu ◽

Wenxue Li ◽

Jiaan Zhu ◽

Fang Liu ◽

Wenting Fan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Remission ◽

Structural Damage ◽

Bone Erosion ◽

Power Doppler ◽

Joint Damage ◽

High Specificity ◽

Predictive Role ◽

Low Sensitivity

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. However, there have been no studies that explored the different time points of ultrasound remission to predict non-progressive structural damage. Given this, the aim of our study is to explore whether early ultrasound remission in patients with rheumatoid arthritis (RA) has predictive value for non-progressive structural damage in the subsequent 12 months. Sixty-one patients with RA were prospectively studied. Synovial hypertrophy, power Doppler (PD) signal, and bone erosions of bilateral wrists, metacarpophalangeal joints I–V, and proximal interphalangeal joints II–III were assessed by ultrasonography at baseline and at 3, 6, and 12 months. Ultrasound remission was defined as no PD signal. Clinical remission was defined as Disease Activity Score in 28 Joints <2.6. Ultrasonography-detected joint damage progression was defined as increase in bone erosion score of ≥1 in the subsequent 12 months. Baseline ultrasonographic factors were not significantly correlated with progressive ultrasonography-detected joint damage in patients with RA at 12 months (all p>0.05). Ultrasound remission at 3 and 6 months was significantly correlated with non-progressive ultrasonography-detected structural damage at 12 months (p=0.006 and p=0.004), with relatively low sensitivity and high specificity. Clinical remission at 3 months was significantly correlated with non-progression of ultrasonography-detected structural damage at 12 months (p=0.029), with relatively low sensitivity and moderate specificity. Ultrasound remission at 3 and 6 months has high specificity in predicting non-progressive structural damage in patients with RA at 12 months; however, the sensitivity is limited.

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POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3850 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 583-583

Author(s):

C. Garufi ◽

F. Ceccarelli ◽

F. R. Spinelli ◽

S. Mancuso ◽

C. Pirone ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Structural Damage ◽

Power Doppler ◽

Response To Treatment ◽

Jak Inhibitors ◽

Inflammatory Score ◽

Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

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Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

Journal of Clinical Medicine ◽

10.3390/jcm10061241 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1241

Author(s):

Yoshiya Tanaka

Keyword(s):

Rheumatoid Arthritis ◽

Structural Damage ◽

Kinase Inhibitors ◽

Joint Destruction ◽

Joint Damage ◽

Nuclear Factor Κb ◽

Cartilage Destruction ◽

Janus Kinase ◽

Systemic Autoimmune Disease ◽

And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

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Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-210311 ◽

2016 ◽

Vol 76 (6) ◽

pp. 992-997 ◽

Cited By ~ 14

Author(s):

Charles Peterfy ◽

Vibeke Strand ◽

Lu Tian ◽

Mikkel Østergaard ◽

Ying Lu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Structural Damage ◽

Randomised Controlled Trials ◽

Task Force ◽

Joint Damage ◽

Controlled Trials ◽

X Rays ◽

X Ray ◽

Pooled Data ◽

Randomised Controlled

ObjectiveIn rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray.MethodsPooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses.ResultsProgression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively).ConclusionsEarly changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs.

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Role of Biological Response Modifiers in the Treatment of Rheumatoid Arthritis - A Review

TAJ Journal of Teachers Association ◽

10.3329/taj.v18i1.3309 ◽

1970 ◽

Vol 18 (1) ◽

pp. 60-65

Author(s):

Md Azizul Haque ◽

ARM Saifuddin Ekram ◽

Quazi Tarikul Islam

Keyword(s):

Rheumatoid Arthritis ◽

Monoclonal Antibody ◽

Chronic Disease ◽

Receptor Antagonist ◽

Disease Progression ◽

Joint Damage ◽

Biological Response ◽

The Past ◽

Conventional Dmards

Rheumatoid arthritis is a chronic disease with the potential to cause substantial joint damage and disability. During the past 10 years, improved understanding of the pathophysiology of rheumatoid arthritis has led to several key changes in the approach to therapy. Most important of that is the development of some biological agents interfering with the activity of several important cytokines. Infliximab, etanarcept, and adalimumab are TNF blockers, anakinra is IL-1 receptor antagonist, and rituximab is anti CD-20 monoclonal antibody. These newer agents proved to be useful for alleviating symptoms and slowing the disease progression in the patients with RA who have failed to respond to conventional DMARDs. doi: 10.3329/taj.v18i1.3309 TAJ 2005; 18(1): 60-65

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The role of HLA typing in rheumatic diseases

Molecular and experimental biology in medicine ◽

10.33602/mebm.3.1.1 ◽

2020 ◽

Vol 3 (1) ◽

pp. 1-8

Author(s):

Luca Mascaretti ◽

Elena Bevilacqua

Keyword(s):

Rheumatoid Arthritis ◽

Juvenile Idiopathic Arthritis ◽

Amino Acid ◽

Ankylosing Spondylitis ◽

Hla Class I ◽

Acid Sites ◽

Hla Typing ◽

Erosive Disease ◽

Complex Cases

Association between HLA-DR4 and rheumatoid arthritis (RA) has been known for 4 decades, and amino acid sites within HLA-DRB1 (11/13, 71, 74) are highly associated with RA. HLA is not useful for diagnosis or prognosis, but it may help predict severe and erosive disease. Since 90% of patients with ankylosing spondylitis (AS) and 50-70% of other spondyloarthritis (SpA) patients are HLA-B*27 positive, HLA is a stronghold of diagnostic algorithms. Genetic predisposition to juvenile idiopathic arthritis (JIA) is mainly due to HLA class II, and to a lesser extent to HLA class I. Although HLA plays a role in rheumatic disorders, its clinical relevance is not homogeneous. When classical biomarkers are lacking or in complex cases, HLA typing may provide support for the management of patients.

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Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218744 ◽

2021 ◽

pp. annrheumdis-2020-218744

Author(s):

Irina Gessl ◽

Mihaela Popescu ◽

Victoria Schimpl ◽

Gabriela Supp ◽

Thomas Deimel ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Power Doppler ◽

Joint Damage ◽

Joint Space ◽

Early Arthritis ◽

Damage Score ◽

Established Disease ◽

Active Inflammation

ObjectivesTo determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness.MethodsPatients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis.ResultsIn total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04).ConclusionTenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.

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Clinical analysis of blood markers and imaging for diagnosis and prognosis of rheumatoid arthritis

10.21203/rs.3.rs-28822/v1 ◽

2020 ◽

Author(s):

Desheng Yang ◽

Haini Li ◽

Shengxia Zhang ◽

Guifeng Yang ◽

Song Liu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Characteristic Curve ◽

Joint Damage ◽

Diagnostic Value ◽

Clinical Analysis ◽

Radiological Outcome ◽

Diagnostic Efficacy ◽

Diagnosis And Prognosis ◽

Imaging Result ◽

Radiological Damage

Abstract Background The purpose of this study is to explore the combined diagnostic value of anti-cyclic citrullinated peptide antibody (A-CCP), rheumatoid factor (RF) and imaging result in early rheumatoid arthritis, and the role of A-CCP and RF in prediction for radiological outcomes. Methods 101 patients with rheumatoid arthritis and 97 control individuals were detect their A-CCP, RF and radiological joint changes, the diagnostic efficacy of the respective indicators and the combined indicators was analyzed by logistic regression model. Results Our results showed that values of A-CCP and RF were significantly higher in the RA group than in the normal group. Receiver operating characteristic curve results show that the sensitivity of RF is higher than A-CCP and radiological outcome, and specificity of CCP is higher than RA and radiological outcome, and the diagnostic ability of combination of RF, A-CCP and radiological outcome is the strongest. Furthermore, RF and A-CCP had high significant OR for radiological joint damage and progression. Conclusions Our study indicated that the combined diagnosis of RF and A-CCP with radiological outcome can improve the diagnostic efficacy of RA, and RF and A-CCP are independent predictors of radiological damage and progression.

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Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators?

Mediators of Inflammation ◽

10.1155/2019/6034546 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Fulvia Ceccarelli ◽

Matteo Saccucci ◽

Gabriele Di Carlo ◽

Ramona Lucchetti ◽

Andrea Pilloni ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Proinflammatory Cytokines ◽

Healthy Subjects ◽

Structural Damage ◽

Genetic Factors ◽

The Many ◽

Citrullinated Peptide ◽

Anticyclic Citrullinated Peptide Antibodies ◽

Peptide Antibodies

The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.

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