CCP Antibodies Research Articles

FRI0165 Boolean definition criteria is useful to predict for bio-free remission in treatment with infliximab for rheumatoid arthritis

BackgroundACR/EULAR definitions of remission is recommended to assess clinical outcome to achieve treat to target for RA treatment (1). However, the role of new remission criteria is not still clear...

AB0329 The new 2010 ACR/eular classification criteria as possible predictor of treatment responses in early RA: Results from the swiss prospective observational RA cohort

BackgroundNew ACR/EULAR criteria for classification of rheumatoid Arthritis (RA) were recently proposed. The aim of this analysis was to examine the impact of fulfilling the 2010 ACR/EULAR criteria at the...

THU0089 Response to abatacept and tocilizumab in patients who had failed rituximab– initial single centre experience

BackgroundInitial reports of biologic therapy (mainly TNF-inhibitor) following B-cell depletion suggest this to be safe and effective 1. Disease which has been refractory to B cell depletion therapy may respond...

SP0098 What is erosive disease in the criteria?

The 1987 ACR criteria for RA consists of several clinical features, RF and also erosive damage on hand radiographs. The new ACR/EULAR criteria have again clinical features and RF and...

THU0453 What is Hidden Under the Palindromic Rheumatism Umbrella?

BackgroundPalindromic rheumatism (PR) is a clinical entity, characterized by multiple, recurrent, transient episodes of arthritis and periarthritis, lasting from hours to days, with spontaneous resolution and symptoms free periods between...

AB0302 Bone texture parameters measured at the hand as predictors of outcome in rheumatoid arthritis

BackgroundBone and cartilage loss and destruction is associated with rheumatoid arthritis (RA) and inflammation. There is a need for tools for prediction of potential severe patients with poor outcome. The...

Post‐translational protein modification in autoimmune epithelitis

Sjögren's syndrome is an autoimmune epithelitis of salivary and lachrymal glands that results in Sicca syndrome. Citrulline is synthesised by the conversion of ornithine to arginine during urea formation, exists as free citrulline produced by NOS enzymes, and another form produced by post‐translational modification of proteins at arginine residues by peptidylarginine deiminases (PADs), which is important in autoimmunity. We investigate post‐translational reactions in salivary gland biopsies from 24 patients with primary Sjögren's syndrome and 24 controls using immunohistochemistry and a tag‐purified anti‐cyclic citrullinated protein CCP antibody to detect citrullinated peptides, PAD2 also was assessed. The present work demonstrated the weak presence of the PAD2 in some normal salivary ducts (10%), although PAD2 expression was increased considerably in Sjögren's patients. The presence of citrullinated proteins in the salivary tissues of Sjögren's patients strongly supports the in situ post‐translational modification of proteins in this setting. The mutual expression of CCP and PAD2 (70%) suggests that this post‐translational modification is enzyme‐dependent. In conclusion, patients with Sjögren's syndrome expressed the catalytic machinery to produce post‐translational reactions that may result in auto‐antigen triggering.Grant: P/PIFI 2011–32MSU0017H‐06–01

White and Blue Fingers: A Red Flag in Sickle Cell Disease

A 34-year-old woman with hemoglobin SC disease had intermittently painful and swollen wrists, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. She photographed her right hand after going outdoors for 10 min (41 °F air temperature). The photograph demonstrated pallor, cyanosis, and erythema (Fig. 1), which abated after 10 min and were unrelated to pain crisis. Based on history and exam, she was diagnosed with Raynaud’s phenomenon. Evaluation revealed an ANA of 1:320 and negative Smith, RF, and CCP antibodies. Anti-RNP was elevated (25 EU/mL), suggesting possible mixed connective tissue disease and secondary Raynaud’s phenomenon. Figure 1. Raynaud’s phenomenon exhibiting acral cyanosis, pallor, and erythema. Hand pain and swelling in sickle cell disease can be from osteonecrosis, osteomyelitis, or hand-foot syndrome during vaso-occlusive crisis (up to 20 % incidence before age two, but rare in adults).1,2 However, Raynaud’s phenomenon is not known to be associated with sickle cell disease, and warrants further investigation for other possible etiologies to avoid misdiagnosis and treatment delays.3 Secondary Raynaud’s may result from vasculopathy, endocrinopathy, drugs, malignancy, or connective tissue diseases. Evaluation may include ESR, ANA, RF, and other disease-specific antibodies (Scleroderma, SLE, MCTD, etc.), as indicated by history. Close monitoring of patients with negative studies may be warranted, as 1 % per year may eventually develop a connective tissue disease.4

Interstitial lung disease in rheumatoid arthritis: an update on diagnosis and management

There has been increasing recognition of the importance of respiratory disease in patients with rheumatoid arthritis (RA) over the last 5 years. Interstitial lung disease (ILD) is the only complication of RA increasing in prevalence and accounts for approximately 6% of all RA deaths, with a mean survival of just 3 years following diagnosis in several historic series. Clinically significant ILD is present in approximately 3–5% of all RA patients, making RA-ILD a common and potentially fatal disorder. Although the presence of RA-ILD increasingly influences therapeutic decision-making, our understanding of its pathogenesis remains limited, as is the evidence base to guide therapeutic intervention. Recent data suggests that RA-ILD may relate to smoking and/or the presence of CCP antibodies. High-resolution computed tomography has allowed clarification of the type and extent of pulmonary involvement without recourse to lung biopsy in most cases. Moreover, the use of certain therapeutic agents may be contraindi...

9G4 expression on autoantibodies to citrullinated peptides in patients with early inflammatory arthritis and established rheumatoid arthritis

BackgroundThe rat monoclonal antibody 9G4 recognises VH4-34-encoded proteins, enabling the identification of inherently autoreactive B cells. In rheumatoid arthritis (RA), evidence for a humoral immune response encoded by VH4-34 gene...

Usefulness of ultrasonographic assessments for the detection of rheumatoid arthritis (RA) during health evaluation and promotion

New criteria for rheumatoid arthritis (RA) were proposed by the ACR/EULAR (American College of Rheumatology/European League against Rheumatism) in 2010 to detect patients with early-stage RA. In this study, the ability of ultrasonographic assessments of the joints to discriminate individuals with RA from those without RA in health evaluation and promotion was investigated. The subjects consisted of 10 patients with morning stiffness and a positive reaction for serum rheumatoid factor. Seven patients were excluded, as they did not have joint swelling according to the newly proposed criteria. The remaining 3 patients had joint swelling and a score of over 6 according to the ACR/EULAR 2010 scoring system. Two patients had blood flow signals when examined using the power Doppler method as well as positive reactions for anti- CCP antibody and acute phase reactants. The other patient did not have a blood flow signal when examined using the power Doppler method and was diagnosed as having Sjögren's syndrome. Ultrasonographic assessments of the joints are useful for identifying individuals with early-stage RA in health evaluation and promotion settings.

Long-term stability of anti-cyclic citrullinated peptide antibody status in patients with early inflammatory polyarthritis

IntroductionThe utility of reassessing anti-cyclic citrullinated peptide (anti-CCP) antibody status later in disease in patients presenting with early undifferentiated inflammatory polyarthritis, particularly in those who test negative for both anti-CCP and rheumatoid factor (RF) at baseline, remains unclear. We aimed therefore to determine the stability of CCP antibody status over time and the prognostic utility of repeated testing in subjects with early inflammatory polyarthritis (IP).MethodsAnti-CCP and RF were measured at baseline and 5 years in 640 IP patients from the Norfolk Arthritis Register, a primary care-based inception cohort. The relation between change in anti-CCP status/titer and the presence of radiologic erosions, the extent of the Larsen score, and Health Assessment Questionnaire (HAQ) score by 5 years was investigated.ResultsWith a cut-off of 5 U/ml, 28% subjects tested positive for anti-CCP antibodies, 29% for RF, and 21% for both at baseline. Nine (2%) anti-CCP-negative patients seroconverted to positive, and nine (4.6%) anti-CCP-positive individuals became negative between baseline and 5 years. In contrast, RF status changed in 17% of subjects. However, change in RF status was strongly linked to baseline anti-CCP status and was not independently associated with outcome. Ever positivity for anti-CCP antibodies by 5 years did not improve prediction of radiographic damage compared with baseline status alone (accuracy, 75% versus 74%). A higher baseline anti-CCP titer (but not change in anti-CCP titer) predicted worse radiologic damage at 5 years (P < 0.0001), even at levels below the cut-off for anti-CCP positivity. Thus, a titer of 2 to 5 U/ml was strongly associated with erosions by 5 years (odds ratio, 3.6 (1.5 to 8.3); P = 0.003).ConclusionsRepeated testing of anti-CCP antibodies or RF in patients with IP does not improve prognostic value and should not be recommended in routine clinical practice.

Increased serum PAD4 and RF in lung cancer is not associated with anti CCP antibody production

BackgroundRheumatoid arthritis (RA) is characterised by anticitrullinated protein antibodies (ACPAs), produced against citrullinated proteins. In the pathogenesis of the disease the interaction of environment and genetics have a role as...

Early undifferentiated arthritis in India: a six month follow up study

Introduction Amongst patients with Early arthritis (EA) only some progress to Rheumatoid arthritis (RA) while the majority continue to remain undifferentiated or undergo spontaneous remission. Viral illness may be responsible for some of the self limiting forms of EA. This study was undertaken to evaluate the aetiology and course of EA from India. Objectives To evaluate the aetiology of EA and identify factors that predicts disease progression to RA at 6 months. Methods Patients with arthritis of 6 weeks to 6 months duration involving > 2 joints were included with age matched healthy controls. The evaluation included plain radiograph of hands, radionuclide bone scan, ESR, CRP, viral markers (Toxoplasma, Rubella, Cytomegalovirus, Herpes simplex, parvovirus, Dengue, Chikungunya, HIV, Hepatitis B & C) and auto antibodies (Anti CCP, RF and ANA). Patients received weekly injectable steroids for 4 weeks with NSAIDs and were followed up for 6 months. Factors that predicted the development to RA were identified. Results Of the 30 patients assessed, majority went into spontaneous remission (23/30) with six developing RA and one developing spondyloarthropathy at 6 months. A viral aetiology could not be ascribed to development of arthritis. The presence of higher swollen Joint Count, higher CRP, RF and anti CCP antibodies, erosions on plain radiograph and a positive bone scan predicted progression to RA. Conclusions Most of EA (almost 80%) is self limiting. Anti CCP antibodies are highly specific for RA and might aid in predicting development of RA.

Hypothyroidism in Noninterferon Treated-HCV Infected Individuals Is Associated with Abnormalities in the Regulation of Th17 Cells

HCV-Ag-specific TH17 cells secrete IL17, a cytokine involved in autoimmune diseases and regulated by IL10 and TGF-b. 5–12% of patients with chronic HCV infection have hypothyroidism. We evaluated the role of these cytokines in this patients by determining serum concentration of TsH, T3, free T4, IL2, IL10, IL12, IL17, TGF-b, anti-TG, TPO, CCP, GBM, and cardiolipin antibodies in 87 chronically noninterferon treated HCV-infected patients. 20 patients (group A) had elevated TsH values (>5 μUI/ml) whereas the remaining 67 (group B) had normal values. The percentage of anti-TPO, TG, GBM, and cardiolipin antibodies in group A patients (33%, 41%, 5% and 5%, resp.) as well as IL17, IL2 and TGF-b concentrations (25 ± 23 pg/ml, 643 ± 572 pg/ml, and 618 ± 221 pg/ml, resp.) were significantly higher than group B. Abnormal Th17 regulation mediated by IL-2 and low TGF-b concentrations is associated with hypothyroidism in chronically-infected HCV patients.

Immunologic rheumatic disorders

We provide the basics for clinicians who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases (ie, RA, seronegative spondyloarthropathy, SLE, antiphospholipid syndrome, Sjögren syndrome, scleroderma, and polymyositis/dermatomyositis) will be covered. In the past decade, treatment for RA and seronegative spondyloarthropathy has substantially improved. Their treatment has been revolutionized by the use of methotrexate and, more recently, TNF inhibitors, T-cell costimulation modulators, and B-cell depletion. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome, SLE, or scleroderma can be identified and then blocked, as in the example of TNF inhibitors in patients with RA, more specific treatments will become available. Thus RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed.

Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study

Objectives:Anti-citrullinated peptide antibodies (ACPAs) are established as useful predictors of radiographic progression in rheumatoid arthritis (RA). The main objective of this study was to test the prognostic capacity of the...

The diagnostic relevance of glucose-6-phosphate isomaerase in patients with rheumatoid arthritis

Objective To assess the levels of glucose-6-phosphate isomerase(GPI) mRNA in peripheral blood monocytes and serum GPI levels in patients with rheumatoid arthritis, and analyze the association of serum GPI with MCV antibody, CCP antibody and RF of RA. Methods Fluorogenic quantitative real-time polymerase chain reaction (FQ-RT-PCR) was used to examine mRNA expression on peripheral blood monocytes in 60 RA patients (28 case in active stage,32 cases in stable stage) ,30 patients with other rheumatic diseases, and 30 healthy controls. ELISA was used to detect the levels of serum GPI, anti-MCV antibodies, anti-CCP antibodies and RF in each group. Results The levels of GPI mRNA in RA group [△Ct=4.21 (3.04-7.23)] were significantly higher than those in patients with other rheumatic diseases [△Ct=8.42 (5.16-9.98),P<0.01] and healthy controls [△Ct=8.66 (4.90-10.01), P<0.01]. There were statistically significant differences of GPI mRNA levels between active RA [△Ct=3.78 (1.28-6.09)] and inactive RA[△Ct =5.88(3.23-8.94),H=11.760,P<0.01)]. The RA group serum GPI levels [3.02 (2.02-8.39) mg/L] were higher than those of other rheumatic diseases [0.20 (0.11-0.32) mg/L] and healthy controls [0.18(0.08-0.30) mg/L]. There were significant differences of serum GPI levels between active RA group [4.84(2.81-10.38) mg/L] and inactive RA group[2.12 (1.26-4.34) mg/L] (H=9.830, P<0.01). The sensitivities of GPI, anti-MCV and anti-CCP were 68% (41/60) ,57% (34/60),58% (35/60), respectively and specificities were 95% (57/60), 92% (55/60) and 93% (56/60), respectively. Conclusions The high expression of GPI mRNA in RA patients shows that it may play a pathological role in the development of RA, and it may be correlated with the activity of RA. It may be a valuable diagnostic parameter for RA, because of its high sensitivity and specificity. Key words: Glucose-6-phosphate isomerase; Arthritis, rheumatoid; Reverse transcription polymerase chain reaction; Enzyme-linked imnunosorbent assay

Usefulness of anti -CCP antibodies in rheumatic diseases in Indian patients

The usefulness of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) to identify rheumatic arthritis (RA) from other rheumatic diseases presenting with joint pain is not well studied. We aimed to determine the sensitivity and specificity of anti-CCP antibodies in Indian RA patients with respect to non-RA rheumatic diseases and to study the relationship of anti-CCP antibodies and IgG, IgM and IgA rheumatoid factor in RA. Case-control cross-sectional study carried out in the rheumatology division of All India Institute of Medical Sciences. Sixty-three patients with rheumatoid arthritis (RA) and 51 patients with non-RA rheumatic diseases having joint pain were included in the study. Sera were tested for anti-CCP antibodies (IgG) and IgA, IgM, IgG rheumatoid factor, using a commercially available enzyme-linked immunosorbent assay. Statistical analysis was performed using SPSS statistical software version 11.5. Fifty-four of 63 RA patients (85.71%) were positive for anti-CCP antibodies. In the non-RA group, anti-CCP antibody was positive in only 5 of 51 patients (9.8%). Our study found a sensitivity of 85% and a specificity of 90.19% with regard to the use of anti-CCP antibodies assay in patients with joint pain to correctly identify RA. Anti-CCP antibodies positive patients did not have more erosive disease. IgM-RF-positive patients had more erosion when compared to the IgM-RF-negative group. Thirty-two of 57 (56.1%) IgM-RF-positive patients had erosions, while no patient (0/6 patients) had erosions in the IgM-RF-negative group (P=0.01) Anti-CCP antibodies have high sensitivity and specificity for diagnosis of RA, in Indian patients. Anti-CCP antibodies positive patients did not have more erosive disease in our study.

Prognoseabschätzung bei früher (rheumatoider) Arthritis – Optimierung durch moderne Bildgebung?

Die Therapie der rheumatoiden Arthritis beginnt für die Patienten mit einer schlechten Prognose heute schon am besten vor der Diagnose, andere Patienten mit der gleichen Diagnose benötigen möglicherweise niemals eine krankheitsmodifizierende Therapie. Klassische Indikatoren für den frühzeitigen Einsatz einer sog. Basistherapie sind die Zahl der geschwollenen Gelenke, die Dauer der Gelenkschwellung, der Nachweis von Rheumafaktoren und/oder CCP-Antikörpern und das Vorhandsein von Erosionen. Die zusammenfassende Bewertung dieser Parameter, z. B. im Visser-Score, erlaubt auch für den Rheumatologen eine gewisse Objektivierung seiner Entscheidung für oder gegen eine Basistherapie bei frühen Verlaufsformen einer Arthritis. In Ergänzung zu den genannten klinischen Parametern ist der initiale Nachweis eines Knochenödems mittels MRT der beste Prädiktor für radiologische Progression. Auch für diese Verlaufbeurteilung sind Ultraschall und MRT wesentlicher sensitiver als sog. Aktivitätsscores. Die Persistenz einer Synovitis und sicher der Nachweis von Knochenödemen bei adäquater Therapie mit klassischen DMARDs könnten Indikation zu einer Therapie mit Biologika sein, deren Effektivität dann auch mittels MRT überprüft werden sollte.