POS0465 DIFFERENT CLINICAL RELEVANCE OF ANTI-CITRULLINATED PROTEINS ANTIBODIES IN RA PATIENTS

Background:Anti-citrullinated proteins antibodies (ACPA) are a broad group of antibodies, including antibodies to citrullinated fibrinogen, antibodies to cyclic citrullinated peptide (anti-CCP), antibodies to modified citrullinated vimentin (anti-MCV), antibodies to citrullinated α-enolase.Objectives:To find a potential relationship between ACPA and disease activity, bone destruction, and ACPAs responses to various therapeutic regimens.Methods:The study included 232 patients (pts) with rheumatoid arthritis (RA); 90 pts (74 women, Me;IQR age 53.0 (38.0–58.5) years had early RA, with mean disease duration 5.0 (4.0–9.0) months, DAS 28 5.3 (4.4–6.1)); 142 pts had advanced stage of the disease (123 women, median age 51.0 (43.0–60.0) years, disease duration 56.0 (24.0–96.0) months, DAS 28 6.2 (5.5–6.8)). Pts with early RA received methotrexate (MTX) subcutaneously at average 17.5 mg dose once weekly. Pts with advanced RA received the following anti-B-cell therapy: 34 pts - rituximab (RTX); 20 pts - RTX biosimilar; 43 pts - tocilizumab (TCZ) in combination with conventional DMARDs. Serum anti-CCP and anti-MCV concentrations were measured using ELISA.Results:77 (85.6%) pts with early RA were high positive for anti-CCP, and 29 (70.7%) pts - high positive for anti-MCV. A positive correlation was found between anti-MCV and DAS 28 (r=0.4, p=0.04). As for advanced RA, 78 (80.4%) pts were high positive for anti-CCP, and 70 (79.5%) - for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r=0.4, p=0.02), as well as CDAI (r=0.4, p=0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0-122.0)) were found in pts high positive for anti-MCV (n=79), compared to low-positive/negative (57.0 (31.0–88.0), respectively, (n=27, p<0.05). anti-MCV levels dropped significantly in pts on RTX and TCZ therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment (Table 1)Conclusion:anti-MCV levels correlated with inflammatory activity and development of bone destruction, and were decreasing in pts on treatment. Anti-CCP was less responsive, showed minor changes during treatment, therefore its’ thorough monitoring was not feasible.Disclosure of Interests:None declared

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Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Anti-Mutated Citrullinated Vimentin (Anti-MCV) Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

Journal of Immunology Research ◽

10.1155/2014/536050 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Laura Gonzalez-Lopez ◽

Alberto Daniel Rocha-Muñoz ◽

Manuel Ponce-Guarneros ◽

Alejandra Flores-Chavez ◽

Mario Salazar-Paramo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Duration ◽

Health Assessment ◽

Serum Levels ◽

Chronic Anemia ◽

Cyclic Citrullinated Peptide ◽

Citrullinated Vimentin ◽

Citrullinated Peptide ◽

Assessment Questionnaire ◽

Questionnaire Disability

We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P=0.40andP=0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P=0.01), anti-CCP (P=0.048), and anti-MCV (P=0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r=0.154,P=0.03), erythrocyte sedimentation rate (ESR); (r=0.155,P=0.03), and RF (P=0.254,P<0.001), whereas anti-MCV titres only correlated with RF (r=0.169,P=0.02). On adjusted analysis, ExRA was associated with longer age (P=0.015), longer disease duration (P=0.007), higher DAS-28 score (P=0.002), and higher HAQ-DI score (P=0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.

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The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-202701 ◽

2013 ◽

Vol 73 (3) ◽

pp. 580-586 ◽

Cited By ~ 56

Author(s):

Paola de Pablo ◽

Thomas Dietrich ◽

Iain L C Chapple ◽

Michael Milward ◽

Muslima Chowdhury ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Negative Control ◽

Autoimmune Response ◽

Serum Samples ◽

Autoantibody Response ◽

Normal Frequency ◽

Citrullinated Proteins ◽

Citrullinated Vimentin ◽

Loss Of Tolerance ◽

Citrullinated Peptide

BackgroundStudies suggest that periodontitis may be a risk factor for rheumatoid arthritis (RA). The purpose of this study was to determine whether periodontitis is associated with autoantibodies characteristic of RA.MethodsSerum samples were tested for anti-cyclic citrullinated peptide (CCP), anti-mutated citrullinated vimentin (MCV), anti-citrullinated α-enolase peptide-1 (CEP-1), anti-citrullinated vimentin (cit-vim), anti-citrullinated fibrinogen (cit-fib) and their uncitrullinated forms anti-CParg (negative control for anti-CCP), anti-arginine-containing α-enolase peptide-1 (REP-1), anti-vimentin and anti-fibrinogen antibodies in patients with and without periodontitis, none of whom had RA.ResultsPeriodontitis, compared with non-periodontitis, was associated with a normal frequency of anti-CCP and anti-MCV (∼1%) but a higher frequency of positive anti-CEP-1 (12% vs 3%; p=0.02) and its uncitrullinated form anti-REP-1 (16% vs 2%; p<0.001). Positive antibodies against uncitrullinated fibrinogen and CParg were also more common among those with periodontitis compared to non-periodontitis patients (26% vs 3%; p<0.001, and 9% vs 3%; p=0.06). After adjusting for confounders, patients with periodontitis had 43% (p=0.03), 71% (p=0.002) and 114% (p<0.001) higher anti-CEP-1, anti-REP-1 and anti-fibrinogen titres, compared with non-periodontitis. Non-smokers with periodontitis, compared with non-periodontitis, had significantly higher titres of anti-CEP-1 (103%, p<0.001), anti-REP-1 (91%, p=0.001), anti-vimentin (87%, p=0.002), and anti-fibrinogen (124%, p<0.001), independent of confounders, confirming that the autoantibody response in periodontitis was not due to smoking.ConclusionsWe have shown that the antibody response in periodontitis is predominantly directed to the uncitrullinated peptides of the RA autoantigens examined in this study. We propose that this loss of tolerance could then lead to epitope spreading to citrullinated epitopes as the autoimmune response in periodontitis evolves into that of presymptomatic RA.

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Association of Anti-Modified Citrullinated Vimentin with Subclinical Atherosclerosis in Early Rheumatoid Arthritis Compared with Anti-Cyclic Citrullinated Peptide

The Journal of Rheumatology ◽

10.3899/jrheum.101143 ◽

2011 ◽

Vol 38 (5) ◽

pp. 828-834 ◽

Cited By ~ 31

Author(s):

AMAL M. El-BARBARY ◽

ELHAM M. KASSEM ◽

MERVAT A.S. El-SERGANY ◽

SALWA A-M. ESSA ◽

MOHAMED A. ELTOMEY

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Sensitivity And Specificity ◽

Early Rheumatoid Arthritis ◽

Subclinical Atherosclerosis ◽

Model Assessment ◽

Early Ra ◽

Das 28 ◽

Tnf Α ◽

Citrullinated Vimentin

Objective.To investigate anti-modified citrullinated vimentin (anti-MCV) in early rheumatoid arthritis (RA), including correlation with disease activity and cardiovascular risk factors, compared with anti-cyclic citrullinated peptides (anti-CCP3).Methods.Anti-MCV and anti-CCP3 concentrations were measured in 100 patients with early RA and 100 healthy controls at baseline to determine sensitivity and specificity. Patients received methotrexate (MTX) 0.2 mg/kg/week plus prednisone 10 mg/day. Anti-MCV, anti-CCP3, rheumatoid factor (RF), Disease Activity Score for 28 joints (DAS-28), lipid profile, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein assay (hsCRP), homeostasis model assessment for insulin resistance (HOMA-IR) index, tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and carotid intima-media thickness (cIMT) were measured before and after 12 months of treatment.Results.The sensitivity and specificity for anti-MCV antibody were 75% and 90%, respectively, and for anti-CCP3 antibody 71% and 96%. Serum anti-MCV and serum anti-CCP3 levels at baseline were positively correlated with hsCRP, IL-6, HOMA-IR index, serum RF levels (p < 0.001), and cIMT (p < 0.05). Serum anti-MCV was positively correlated with serum anti-CCP3 levels. There were significant positive correlations between the percentage of changes of anti-MCV levels versus changes in DAS-28, ESR, hsCRP, atherogenic ratios (TC/HDL-C and LDL-C/HDL-C), apolipoprotein A-I, IL-6, TNF-α, HOMA-IR index, and cIMT. These correlations were not found between changes in anti-CCP3 levels compared to clinical, laboratory, and radiological variables.Conclusion.Anti-MCV was as sensitive as anti-CCP3 in diagnosing early RA. Anti-MCV testing appears to be useful for monitoring associated subclinical atherosclerosis in early RA.

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Can Cytokines be used as an Activation Marker in Rheumatoid Arthritis?

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666201019115030 ◽

2020 ◽

Vol 20 ◽

Author(s):

Fatih Öner Kaya ◽

Yeşim Ceylaner ◽

Belkız Öngen İpek ◽

Zeynep Güneş Özünal ◽

Gülbüz Sezgin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Healthy Volunteers ◽

Venous Blood ◽

Cross Sectional Study ◽

Joint Disease ◽

Control Group ◽

Cross Sectional ◽

Positive Correlation ◽

Das 28 ◽

Tnf Α

Aims: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines takes an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. Background: RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as a primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. Objective: In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. Methods: This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. Results: RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA according to RA in remission (p=0.03). DAS-28 was significantly high in active RA according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). Conclusion: TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.

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THU0484 FIBROMYALGIA AND MULTIPLE SWITCHING OF BIOLOGICS IN SPONDYLOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6224 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 479.2-480

Author(s):

A. Negm ◽

J. Alsaleh

Keyword(s):

Bone Marrow ◽

Disease Activity ◽

Bone Marrow Edema ◽

Disease Duration ◽

Hla B27 ◽

Tender Points ◽

Conventional Dmards ◽

Likelihood Ratio Testing ◽

Multiple Switching ◽

Marrow Edema

Background:Fibromyalgia (FM) is a condition characterized by chronic widespread pain, tender points, fatigue and disturbed sleep rhythm. Some of these symptoms such as fatigue, tender points and diffuse pain seen in patients with spondylarthritis (SpA). Moreover, FM and SpA can coexist creating a diagnostic challenge, particularly in early disease course and influence clinical disease activity assessment.Objectives:With this cross-sectional study, we aim to estimate the prevalence of FM in SpA and to elaborate its effect on biological treatments.Methods:FM was identified according to the ACR 2010 diagnostic criteria. SpA patients identified according to rheumatologist using various SpA subsets criteria. A review of the electronic medical files for SpA patients attending the rheumatology outpatient clinic and infusion unit at a major tertiary hospital during the period from June to December 2018 were included. Patients’ demographics, socioeconomics, disease characteristics, activity, HLA status and abnormal MRI sacroiliac were explored. Regarding SpA medications, number, frequency and dose of DMARDs and biological agents were obtained.Continuous variables were reported by their mean and standard deviation (SD) and qualitative variables by frequency and percentage. Statistical significance was set at p <0.05. Statistical analysis was performed using SPSS version 23.Results:Of the 305 enrolled SpA patients, 43 (14.1%) had FM. Females represents 57.4% of the patients, mean age was 44.07 ± 11.85 years. Arab ethnicity represents most of our cohort 84.9%, the majority were Emirati 64.6%. Smokers were 8.2% and ex-smokers were 3.3%. Axial SpA represents 38.4% while peripheral SpA 61.6% of our cohort according to ASAS classification.HLA B27 tested in a sample of 180 patients; it was positive in only 17.8%. CRP found to be elevated in 20.3% of the patients at baseline. Abnormal MRI SIJ bone marrow edema changes were found in 10.8%, while other SIJ changes was seen in additional 20.6%. The prevalence of FM showed no statistically significant difference between axial and peripheral SpA. Patients SpA and FM have longer disease duration than SpA alone, P= 0.034. Table.1 show demographics, socioeconomics and clinical data of our cohort.Regarding medication, the use of biologics among SpA patients with FM is more frequent than SpA patients without FM (74.4% vs 51.5 % respectively), P= 0.005. Interestingly, the likelihood ratio testing showed that SpA patient with Fibromyalgia switch more frequently to another biologics than SpA without fibromyalgia, P= 0.015.Cramer’s V test showed that there is a high statistically significant (P= 0.002) and very strong association (> 0.25) between presence of Fibromyalgia and multiple switching of biologics in SpA.There was no difference in the exposure to prednisolone nor conventional DMARDs between SpA patients with or without FM, P= 0.64 & 1 respectively.Gender, Female, n (%)175 (57.4)Age, mean ± SD (min- max), years44.07 ± 11.85 (18- 78)Type of A, n (%)AxialPeripheral117 (38.4)188 (61.6)Fibromyalgia, n (%)FM in axial SpAFM in Peripheral SpA43 (14.1)18 (41.9)25 (58.1)SpA Disease duration (months)FM+, mean ±SDFM-, mean ±SD107.7± 50.486± 57.9Elevated CRP, n (%)62 (20.3)HLA B27 in180 patients, n (%)PositiveNegative32 (17.8)148 (82.2)Abnormal MRI SIJ, n (%)Bone marrow edemaSubchondral sclerosisFatty transformation of bone marrowErosion92 (30.2)33 (10.8)21 (6.9)5 (1.6)2 (0.7)Number of conventional DMARDs ever tired, n (%)NoneOneTwoThree81 (26.6)166 (54.4)46 (15.1)12 (3.9)Frequency of DMARDs usage, n, (%)Conventional DMARDsPrednisoloneBiologic DNARDs224 (73.4)56 (18.4)164 (53.8)Conclusion:FM coexistence with SpA might impact clinical evaluation of disease activity and possibly negatively affect self-measurement of treatment response. In our study, SPA patients exposed to more biologics if they have coexisting FM; Moreover, they are more frequent switchers among biologics including TNFi and IL17i.Acknowledgments:N Elsidig, A Al Marzooqi, N Zamani, A HossainiDisclosure of Interests: :None declared

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AB0224 ASSOCIATIONS BETWEEN JOINT REPLACEMENT HISTORY AND CYCLIC CITRULLINATED PEPTIDE ANTIBODY TITERS IN RHEUMATOID ARTHRITIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3981 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1412.2-1412

Author(s):

M. Sato ◽

M. Takemura

Keyword(s):

Rheumatoid Arthritis ◽

Joint Replacement ◽

Disease Duration ◽

Certolizumab Pegol ◽

Biologic Agent ◽

Cyclic Citrullinated Peptide ◽

Replacement Procedure ◽

Antibody Titers ◽

Age Range ◽

Citrullinated Peptide

Background:High titers of cyclic citrullinated peptide antibodies (anti-CCP) are predictive of poor prognosis in the treatment of rheumatoid arthritis (RA). The 2010 ACR/EULAR classification criteria for early RA assign a high point value to cases having highly positive anti-CCP titers. Previous reports have claimed that osteoarthritic damage is more severe and advanced in RA patients who test positive for anti-CCP than in their negative counterparts.Objectives:To retrospectively investigate whether anti-CCP titers were associated with the extent of osteoarthritic damage in RA patients treated at our institution.Methods:Data were analyzed for 422 RA patients who received biologic agents due to resistance to methotrexate or other conventional antirheumatic drugs. Associations were explored between joint replacement history-i.e. total knee replacement (TKR), total hip replacement (THR), or lack thereof—and anti-CCP positivity rates and titers.Results:The sample consisted of 90 men and 332 women. On average, patients were put on biologics at 58.6 years of age (range: 22–85), and had a disease duration of 9.3 years. The first biologic agent chosen was infliximab (IFX) in 154 cases, etanercept (ETN) in 76, adalimumab (ADA) in 61, tocilizumab (TCZ) in 70, abatacept (ABT) in 41, golimumab (GLM) in 18, and certolizumab pegol (CZP) in 2. In total, 331/422 patients (78.4%) tested positive for anti-CCP. TKR was performed in 46 cases (M:F ratio: 7:39, mean age: 64.7 y, mean disease duration: 15.1 y), of which 46 were positive for anti-CCP (100%). THR was performed in 18 cases (M:F ratio: 2:16, mean age: 62.3 y, mean disease duration: 18.5 y), of which 17 were positive for anti-CCP (94.4%). The mean anti-CCP titer among all positive patients (n=331) was 152.9 IU/ml. This value was significantly higher in patients who underwent either joint replacement procedure than those who did not (215.4 v. 142.8 IU/ml, p<0.0005).Conclusion:With one exception, all RA patients who underwent joint replacement were positive for anti-CCP, and their titers were higher than non-surgical cases. Practitioners should be aware of this trend, and pay attention to the progression of damage in the knee and hip joints when treating RA patients with high anti-CCP titers.Disclosure of Interests:None declared

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Anti-CCP Antibody Levels Are Not Associated with MS: Results from a Case-Control Study

BioMed Research International ◽

10.1155/2015/817427 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Mahmut Alpayci ◽

Aysel Milanlioglu ◽

Veysel Delen ◽

Mehmet Nuri Aydin ◽

Huseyin Guducuoglu ◽

...

Keyword(s):

Case Control Study ◽

Critical Role ◽

Positive Association ◽

Case Control ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Citrullinated Proteins ◽

Antibody Levels ◽

Citrullinated Peptide ◽

Control Study

Citrullinated proteins have been suggested to play a critical role in the pathogenesis of multiple sclerosis (MS). Anticyclic citrullinated peptide (anti-CCP) antibody is used in the early diagnosis of rheumatoid arthritis (RA). The objective of this study was to investigate the presence of anti-CCP antibody in patients with MS compared to RA patients and healthy controls. Fifty patients with MS (38 females, 12 males; mean age 36.72 ± 8.82 years), 52 patients with RA (40 females, 12 males; mean age 40.87 ± 10.17 years), and 50 healthy controls (32 females, 18 males; mean age 38.22 ± 11.59 years) were included in this study. The levels of serum anti-CCP antibody were measured using an enzyme-linked immunosorbent assay (ELISA). The results of the study showed that anti-CCP antibody levels were significantly higher in RA patients versus MS or healthy controls(P<0.001). Moreover, anti-CCP antibody was positive in 43 (83%) patients with RA, while it was negative in all MS patients as well as in all healthy controls. Also, no significant correlation was found between the anti-CCP levels and EDSS scores(r=-0.250). In conclusion, the results of this study did not support a positive association between serum anti-CCP antibody and MS.

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Higher Mortality and Infection Rate in a Region or Country Suggest a Longer Time of COVID-19 Disease Pandemic

10.21203/rs.3.rs-34706/v1 ◽

2020 ◽

Author(s):

Tianshu Gu ◽

Lan Yao ◽

Tong Sun ◽

Sara W. Day ◽

Scott C. Howard ◽

...

Keyword(s):

Infection Rate ◽

Death Rate ◽

Positive Relationship ◽

Disease Duration ◽

Strong Positive Correlation ◽

Positive Correlation ◽

Number Of Patients ◽

The World ◽

Total Death ◽

R Value

Abstract In view of the fact that the 2019-nCoV has spread to most countries in the world, it is necessary to make scientific and well-founded predictions of the current pandemic situation caused by the virus worldwide, which are conducive to public, social and government responses that mitigate and appropriately address the pandemic. We collected data from provinces with more than 200 cases in China and from eight other countries. Our analyses showed that the disease duration has no correlation with the number of patients, with r = 0.184. The number of deaths was not correlated to the disease duration, with r = 0.242. However, a positive correlation between the days of disease duration and infection rate, with a r = 0.626. Furthermore, there is a strong positive correlation between the disease duration and total death rate, with a r = 0.707. Using death rate of first 25 days, we obtained a positive relationship with a r value of 0.597. Based on the data from first 25 days, the minimum and maximum days of COVID-19 pandemic duration of eight countries was estimated between days of 37 and 114 days.

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