scholarly journals Autoantibodies to Peptidylarginine Deiminase 2 Are Associated With Less Severe Disease in Rheumatoid Arthritis

2018 ◽  
Vol 9 ◽  
Author(s):  
Erika Darrah ◽  
Jon T. Giles ◽  
Ryan L. Davis ◽  
Pooja Naik ◽  
Hong Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Peptidylarginine Deiminase

Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis treated with tumour necrosis factor-α blocking agents

2008 ◽  
Vol 68 (2) ◽  
pp. 249-252 ◽  
Author(s):  
E H Halvorsen ◽  
E A Haavardsholm ◽  
S Pollmann ◽  
A Boonen ◽  
D van der Heijde ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Severe Disease ◽  
Peptidylarginine Deiminase ◽  
Association Analyses ◽  
Peptidylarginine Deiminase 4 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Background:Peptidylarginine deiminase 4 (PAD4) may generate epitopes targeted by anticitrullinated protein antibodies in rheumatoid arthritis (RA). A subset of patients with RA has serum autoantibodies to human recombinant PAD4 (hPAD4). Here, we assessed whether anti-hPAD4 status in RA predicted disease outcome after antitumour necrosis factor (anti-TNF)-α therapy.Methods:We analysed RA sera obtained at baseline (n = 40) and after 1 year on anti-TNF-α therapy (n = 33) for anti-hPAD4 IgG. Association analyses between baseline anti-hPAD status and disease progression were performed.Results:We found that 17 of 40 patients (42.5%) were serum anti-hPAD4 positive at baseline, and the anti-hPAD4 IgG levels were stable over 1 year on anti-TNF-α therapy. At baseline, there were indications that anti-hPAD4 positive patients had more severe disease than the negative patients. After 1 year on anti-TNF-α therapy, the anti-hPAD4 positive patients displayed a persistently elevated disease activity score using 28 joint counts score and increased progression in the van der Heijde–modified Sharp erosion score. Accordingly, more anti-hPAD4 positive than negative patients presented an increase in van der Heijde–modified Sharp erosion scores >0 over 1 year.Conclusions:Anti-hPAD4 IgG can be detected in a subset of RA sera and the levels are stable after initiation of anti-TNF-α therapy. Serum anti-hPAD4 may predict persistent disease activity and radiographic progression in patients with RA receiving anti-TNF-α therapy.

scholarly journals Anti-peptidylarginine deiminase-4 antibodies at mucosal sites can activate peptidylarginine deiminase-4 enzyme activity in rheumatoid arthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
M. Kristen Demoruelle ◽  
Hong Wang ◽  
Ryan L. Davis ◽  
Ashley Visser ◽  
Johnny Hoang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
At Risk ◽  
Enzymatic Activity ◽  
Severe Disease ◽  
Active Role ◽  
Peptidylarginine Deiminase ◽  
Peptidylarginine Deiminase 4 ◽  
Healthy Control ◽  
Paired Serum ◽  
Representative Samples

Abstract Background Mucosal sites are hypothesized to play a role in the development of rheumatoid arthritis (RA). Since serum anti-peptidylarginine deiminase (PAD)4 antibodies, including a subset that cross-react with PAD3 (PAD3/4), are specific for RA and associate with severe disease, we sought to examine whether anti-PAD4 and anti-PAD3/4 antibodies were present in the lung and oral mucosa of subjects with RA and “at-risk” for RA. Methods We included 37 RA, 25 healthy control, and 46 subjects “at-risk” for RA based on familial RA and/or serum anti-citrullinated protein antibody (ACPA) positivity. Paired serum, sputum, and saliva were evaluated for anti-PAD4 and anti-PAD3/4 using immunoprecipitation and ACPA using ELISA. Immunoglobulins (Ig) were purified from representative samples, and their effect on citrullination of histone H3 by recombinant human PAD4 was measured by anti-citH3 immunoblot. Results Anti-PAD4 antibodies were detected in the serum of 6/37 (16.2%), sputum of 3/37 (8.1%), and saliva of 3/33 (9.1%) RA subjects and in the serum and sputum of 1/46 (2.2%) at-risk subjects. None of the healthy controls had anti-PAD4 antibodies at any site. Serum, sputum, and salivary anti-PAD4 antibodies were more prevalent in RA subjects with RA duration >2 years. Purified antibodies from representative anti-PAD4-positive and anti-PAD3/4-positive sputum were primarily of the IgA isotype and able to increase PAD4 enzymatic activity. Conclusions Anti-PAD4 antibodies are present in the sputum and saliva of a portion of RA patients and are infrequent in at-risk subjects. Importantly, the ability of anti-PAD4, and particularly anti-PAD3/4, antibodies in the sputum to enhance PAD4 enzymatic activity suggests that anti-PAD4 may play an active role in the RA lung.

scholarly journals Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Antonio Julià ◽  
María López-Lasanta ◽  
Francisco Blanco ◽  
Antonio Gómez ◽  
Isabel Haro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Retrospective Cohort ◽  
Tumor Necrosis ◽  
Peptidylarginine Deiminase ◽  
Das28 Score ◽  
Factor Therapy ◽  
Interaction Term ◽  
Antibody Interactions ◽  
Necrosis Factor

Abstract Background Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. Methods For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. Results The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). Conclusions The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.

Patients with Rheumatoid Arthritis in Clinical Remission Manifest Persistent Joint Inflammation on Histology and Imaging Studies

2014 ◽  
Vol 41 (11) ◽  
pp. 2153-2160 ◽  
Author(s):  
Allen Anandarajah ◽  
Ralf Thiele ◽  
Ellen Giampoli ◽  
Johnny Monu ◽  
Gwy-Suk Seo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Remission ◽  
Severe Disease ◽  
Joint Inflammation ◽  
Imaging Studies ◽  
American College Of Rheumatology ◽  
Remission Criteria ◽  
Magnetic Resonance Imaging Mri ◽  
Active Inflammation

Objective.The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology.Methods.We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined.Results.Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US.Conclusion.Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.

scholarly journals Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 629-639 ◽  
Author(s):  
Mark C. Genovese ◽  
César Pacheco Tena ◽  
Arturo Covarrubias ◽  
Gustavo Leon ◽  
Eduardo Mysler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Incidence Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

scholarly journals Microalbuminuria: A marker of severe disease activity in rheumatoid arthritis

2013 ◽  
Vol 8 (3) ◽  
pp. 112-116 ◽  
Author(s):  
Monica Verma ◽  
Vijay Shanker ◽  
Harpreet Singh ◽  
Abhishek Soni ◽  
Himanshu Madaan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Severe Disease

Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associations with disease severity

2007 ◽  
Vol 67 (3) ◽  
pp. 414-417 ◽  
Author(s):  
E H Halvorsen ◽  
S Pollmann ◽  
I-M Gilboe ◽  
D van der Heijde ◽  
R Landewe ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Severity ◽  
Igg Antibodies ◽  
Peptidylarginine Deiminase ◽  
Peptidylarginine Deiminase 4 ◽  
Serum Igg

scholarly journals Vitamin D as a novel therapy in inflammatory bowel disease: new hope or false dawn?

2014 ◽  
Vol 74 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Maria O'Sullivan
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Bowel Disease ◽  
Complex Disease ◽  
Therapeutic Potential ◽  
Severe Disease ◽  
Novel Therapy ◽  
Vitamin D Levels ◽  
Inflammatory Bowel

There is increasing scientific interest in the field of vitamin D research, moving the focus beyond bone health to other disease processes. Low circulating vitamin D levels have been reported as a risk factor for several pathophysiologically divergent diseases, including cancers, diabetes, CVD, multiple sclerosis and inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease (IBD). But, therein, remains the challenge: can any single nutrient contribute to multiple complex disease mechanisms and, ultimately, have therapeutic potential? The aim of this review is to critically evaluate several strands of scientific evidence surrounding vitamin D and inflammation, primarily focusing on IBD. Epidemiological studies suggest an increased incidence of IBD and rheumatoid arthritis in countries of more northern latitudes, mirroring sunlight patterns. A considerable body of evidence supports the anti-inflammatory effects of vitamin D, at least in animal models of IBD. Although it is accepted that suboptimal vitamin D status is common in IBD, some studies suggest that this associates with more severe disease. With regard to treatment, the data are only beginning to emerge from randomised controlled trials to suggest that people with IBD may remain in remission longer when treated with oral vitamin D. In conclusion, several strands of evidence suggest that vitamin D may modify the immune response in IBD. There is a continued need for large well-designed clinical trials and mechanistic studies to determine if, and how, this emerging promise translates into tangible clinical benefits for people with chronic debilitating diseases such as IBD.

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