scholarly journals Identification of a Novel Serological Marker in Seronegative Rheumatoid Arthritis Using the Peptide Library Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Caterina Bason ◽  
Alessandro Barbieri ◽  
Nicola Martinelli ◽  
Bianca Olivieri ◽  
Giuseppe Argentino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Subjects ◽  
Cytotoxic T Lymphocyte ◽  
Bone Destruction ◽  
Peptide Library ◽  
Arginine Deiminase ◽  
Systemic Autoimmune Disease ◽  
Random Peptide Library ◽  
Tyrosine Kinase 2 ◽  
Peptide Antibodies

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation mainly affecting the joints leading to cartilage and bone destruction. The definition of seropositive or seronegative RA is based on the presence or absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs). Other autoantibodies have been identified in the last decade such as antibodies directed against carbamylated antigens, peptidyl-arginine deiminase type 4 and v-Raf murine sarcoma viral oncogene homologue B. In order to identify relevant autoantigens, we screened a random peptide library (RPL) with pooled IgGs obtained from 50 patients with seronegative RA. Patients’ sera were then used in an ELISA test to identify the most frequently recognized peptide among those obtained by screening the RPL. Sera from age- and sex-matched healthy subjects were used as controls. We identified a specific peptide (RA-peptide) recognized by RA patients’ sera, but not by healthy subjects or by patients with other immune-mediated diseases. The majority of sera from seronegative and seropositive RA patients (73.8% and 63.6% respectively) contained IgG antibodies directed against the RA-peptide. Interestingly, this peptide shares homology with some self-antigens, such as Protein-tyrosine kinase 2 beta, B cell scaffold protein, Liprin-alfa1 and Cytotoxic T lymphocyte protein 4. Affinity purified anti-RA-peptide antibodies were able to cross react with these autoantigens. In conclusion, we identified a peptide that is recognized by seropositive and, most importantly, by seronegative RA patients’ sera, but not by healthy subjects, conferring to this epitope a high degree of specificity. This peptide shares also homology with other autoantigens which can be recognized by autoantibodies present in seronegative RA sera. These newly identified autoantibodies, although present also in a percentage of seropositive RA patients, may be considered as novel serum biomarkers for seronegative RA, which lacks the presence of RF and/or ACPAs.

scholarly journals Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators?

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
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.

scholarly journals Rheumatoid Factors: Clinical Applications

2013 ◽  
Vol 35 ◽  
pp. 727-734 ◽  
Author(s):  
Francesca Ingegnoli ◽  
Roberto Castelli ◽  
Roberta Gualtierotti
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Subjects ◽  
Therapeutic Strategy ◽  
Clinical Applications ◽  
Rheumatoid Factors ◽  
Cyclic Citrullinated Peptide ◽  
Rheumatoid Factor Isotypes ◽  
Form Part ◽  
Citrullinated Peptide ◽  
Peptide Antibodies

Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.

scholarly journals Pharmacokinetics-Based Chronoefficacy of Semen Strychni and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingpan Lin ◽  
Lu Gao ◽  
Yanke Lin ◽  
Shuai Wang ◽  
Zemin Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Destruction ◽  
Systemic Exposure ◽  
Inflammatory Factors ◽  
Systemic Autoimmune Disease ◽  
Active Ingredients ◽  
Tnf Α ◽  
Exposure Levels ◽  
Semen Strychni

Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.

scholarly journals Dietary Habits and Nutrition in Rheumatoid Arthritis: Can Diet Influence Disease Development and Clinical Manifestations?

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1456 ◽  
Author(s):  
Chiara Gioia ◽  
Bruno Lucchino ◽  
Maria Grazia Tarsitano ◽  
Cristina Iannuccelli ◽  
Manuela Di Franco
Keyword(s):  
Rheumatoid Arthritis ◽  
Dietary Habits ◽  
Disease Risk ◽  
Harmful Effect ◽  
Antioxidant Properties ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Systemic Autoimmune Disease ◽  
Joint Involvement ◽  
Protective Effects

Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by joint involvement, with progressive cartilage and bone destruction. Genetic and environmental factors determine RA susceptibility. In recent years, an increasing number of studies suggested that diet has a central role in disease risk and progression. Several nutrients, such as polyunsaturated fatty acids, present anti-inflammatory and antioxidant properties, featuring a protective role for RA development, while others such as red meat and salt have a harmful effect. Gut microbiota alteration and body composition modifications are indirect mechanisms of how diet influences RA onset and progression. Possible protective effects of some dietary patterns and supplements, such as the Mediterranean Diet (MD), vitamin D and probiotics, could be a possible future adjunctive therapy to standard RA treatment. Therefore, a healthy lifestyle and nutrition have to be encouraged in patients with RA.

scholarly journals Higher Serum CCN3 Is Associated with Disease Activity and Inflammatory Markers in Rheumatoid Arthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yingying Wei ◽  
Linan Peng ◽  
Yi Li ◽  
Na Zhang ◽  
Ke Shang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cancer Metastasis ◽  
Foam Cell ◽  
Alveolar Epithelial Cell ◽  
Bone Destruction ◽  
Serum Levels ◽  
Joint Disease ◽  
Systemic Autoimmune Disease ◽  
Foam Cell Formation

Nephroblastoma overexpressed protein (NOV/CCN3), the early discovered member of the CCN family, has recently been suggested to be involved in a number of inflammatory processes, including wound healing, alveolar epithelial cell inflammation, cancer metastasis, and macrophage foam cell formation. However, the role of CCN3 in rheumatoid arthritis (RA), a classic autoimmune and inflammatory disease, remains elusive. RA is a chronic systemic autoimmune disease that eventually leads to cartilage and bone destruction and joint dysfunction. In this study, we investigated the potential of serum CCN3 as a biomarker for RA. The serum levels of CCN3 were measured by ELISA. The clinical and laboratory parameters were collected from a clinical record system, and disease activity was determined by joint disease activity score 28 (DAS28). Our results showed that the serum levels of CCN3 were significantly increased in RA patients compared to healthy controls. Furthermore, the CCN3 level was positively correlated with DAS28 (CRP), DAS28 (ESR), and the level of anti-CCP Ab, an autoantibody highly specific for RA. Furthermore, CCN3 showed a positive correlation with inflammatory cytokine IL-6, while no significant correlation with TNF-α was observed. These data suggest that CCN3 plays an important role in the development of RA and might be a potential disease activity biomarker for RA.

The Impact of Proinflammatory Cytokynes of Rheumatoid Polyarthritis on the Generalized Loss of Bone Mass

2018 ◽  
Vol 69 (9) ◽  
pp. 2541-2545
Author(s):  
Raluca Barzoi ◽  
Elena Rezus ◽  
Codruta Badescu ◽  
Razan Al Namat ◽  
Manuela Ciocoiu
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cells ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Nuclear Factor ◽  
Receptor Activator ◽  
Level Function ◽  
Rheumatoid Polyarthritis ◽  
The Impact ◽  
Nuclear Factor Kb

There is a bidirectional interaction between most immune cells and osteoblasts, osteoclasts and their precursor cells. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK/osteoprotegerin (OPG) system plays an essential role in the formation of osteoblasts, but it also has implications in osteoclast biology and implicitly on the diseases characterized by bone loss. Proinflammatory cytokines existing at synovial level function as direct or indirect stimulators of osteoclast differentiation, but also of its survival or activity, although some cytokines may also play an antiosteocastogenic role. The fate of bone destruction is determined by the balance between osteoclastogenic and antiosteoclastogenic mediators. Our study has shown that the early initiation of the therapy with anti-TNF and anti-IL6 biological agents, in patients with rheumatoid arthritis, inhibits bone destruction, regardless of the anti-inflammatory activity in patients with rheumatoid arthritis.

scholarly journals FRI0127 Suppression of radiographic progression after gradual methotrexate tapering in patients with rheumatoid arthritis patients maintaining low disease activity - Prospective multicenter study-

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 645.1-645
Author(s):  
K. Katayama ◽  
K. Yujiro ◽  
T. Okubo ◽  
R. Fukai ◽  
T. Sato ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Destruction ◽  
Reduction Rate ◽  
Bone Destruction ◽  
High Response ◽  
Continuation Rate ◽  
Low Disease Activity ◽  
One Year ◽  
Response Group

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared

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

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.

scholarly journals AB0162 OCULAR MANIFESTATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1108.1-1108
Author(s):  
D. Monova ◽  
S. Monov ◽  
R. Shumnalieva ◽  
D. Dimova ◽  
M. Sotirova
Keyword(s):  
Rheumatoid Arthritis ◽  
Intraocular Pressure ◽  
Disease Duration ◽  
Keratoconjunctivitis Sicca ◽  
Retinal Vasculitis ◽  
Standard Test ◽  
Systemic Autoimmune Disease ◽  
Ophthalmological Examination ◽  
Schirmer’S Test ◽  
Ocular Symptoms

Background:Rheumatoid arthritis (RA) is the most common systemic autoimmune disease and is associated with a number of extra-articular organ manifestations, including ocular complications.Objectives:The aim of this study is to evaluate the frequency and characteristics of ocular manifestation in patients with rheumatoid arthritis (RA).Methods:The study involved 87 patients with RA. All the study subjects underwent complete ophthalmological examination involving visual acuity assessment, examination of anterior and posterior eye segments, Schirmer’s test, diameter and mobility of pupils, as well as eyeball mobility assessment of intraocular pressure. Data regarding age, gender, disease duration, age at diagnosis, systemic corticosteroid use, blood pressure, ocular symptoms and detailed ophthalmic history were recorded. The presence of rheumatoid factor in serum was evaluated by standard test methods based on principle of agglutination. All patients were seropositive.Results:87 patients (26 male, 59 female, mean age 45,6 ± 13,1 years; mean disease duration 7,4 ± 6,2 years) with RA were enrolled in this study. 31 (35,63 %) of them had no ocular symptoms. Among the patients with ocular symptoms, 39 (69,64 %) complained of decreased vision, 33 (58,93 %) - of dry eye, 32 (57,14 %) - of burning, 29 (51,78 %) -photophobia, 28 (50 %) - of gritty sensation, 27 (48,21 %) - of itching, 18 (32,14 %) - of redness, 13 (23,21 %) - of ocular pain, 3 (5,36 %) - of floaters. Ophthalmological examination revealed higher incidence of the following abnormalities in the study group: myopic astigmatism - in 10 (5,74 %) eyes, vascular abnormalities within fundus - in 22 (12,64 %) eyes, increased intraocular pressure (> 21 mm Hg) - in 11 (6,32 %) eyes. Mean IOP values were 17,34 ± 5,12 mm Hg. In 48 eyes Schirmer’s test results were below 10 mm, and in 18 eyes - below 5 mm. Keratoconjunctivitis sicca was present in 31 (35,63 %) of all patients. Episcleritis was diagnosed in 4 patients (4,6 %), scleritis – in 3 (3,45 %). Retinal vasculitis was present in 2 (2,3 %) patients and involves veins and arteries peripheral branches. Lens opacity was found in 13 (14,94 %) patients (21 eyes), mostly in the form of posterior subcapsular cataract (in 16 eyes) and nuclear cataract (in 5 eyes). The mean age of patients with cataracts was 52,3 ± 14,2 years. 13 of the patients with cataracts were either currently taking or had previously taken systemic corticosteroids.Conclusion:In patients with RA numerous abnormalities within the vision of organ may be found. Ocular symptoms are relatively common complications of RA, and may result in irreversible changes in the organ of vision. Regular ophthalmological examinations are essential among the patients with RA.Disclosure of Interests:None declared

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