anti-CCP Antibody Titers Research Articles

Scleroderma overlap syndromes

Scleroderma overlap syndromes

HLA-DRB1 alleles in Egyptian rheumatoid arthritis patients: Relations to anti-cyclic citrullinated peptide antibodies, disease activity and severity

BackgroundHuman leukocyte antigen HLA-DRB1 alleles encoding a common amino acid sequence called shared epitope in the third hypervariable region of DRB1 molecule have been identified as risk alleles for rheumatoid arthritis (RA). Aim of the workThe aim was to study HLA-DRB1 01, 04 and 10 alleles in Egyptian RA patients and determine their relation with anticyclic citrullinated peptide (anti-CCP) antibody level, disease activity, clinical and radiological severity. Patients and methodsThe study involved 40 RA patients and 20 control. Simplified disease activity index (SDAI) was calculated, clinical severity was assessed using the mechanical joint score (MJS) and radiological severity evaluated using the simple erosion narrowing score (SENS). HLA-DRB1 genotyping and anti-CCP antibodies were detected. ResultsThe mean patients’ age was 41.6±12.7years and disease duration 8.9±7.7years. The frequency of HLA DRB1 01, 04 and 10 in patients was 42.5%, 60% and 25% respectively. Of them 04 was significantly higher than in controls (p=0.013) and was associated with anti-CCP positive cases (p=0.0008) while the absence of HLA-DRB1 alleles was significantly associated with negative anti-CCP negative RA (p=0.0008). There were significant associations between HLA-DRB1 01 and 04 with SDAI (p=0.0002 and p=0.005, respectively); between HLA-DRB1 04 and 10 with SENS (p=0.002 and p=0.001 respectively) and between HLA-DRB1 01, 04 and 10 with MJS (p=0.02, p=0.03 and p=0.02, respectively). ConclusionHLA-DRB1 04 is associated with RA in Egyptian patients and is strongly associated in the production of elevated titers of anti-CCP antibodies which contribute to the development, severity and activity of the disease.

Anticyclic citrullinated peptide antibody in rheumatoid arthritis:a cross-sectional study in Iran.

Studies have shown that anticyclic citrullinated peptide antibody (anti-CCP) titers can be useful in the diagnosis of rheumatoid arthritis (RA). We evaluate the association between anti-CCP antibody titers and the demographic, clinical, and laboratory characteristics of RA patients. Moreover, we explore whether there is any relation between joint destruction and demographic and clinical characteristics of RA patients. One hundred and four RA patients with positive anti-CCP titers were compared to 104 RA patients with negative anti-CCP titers. The activity of RA was evaluated using the Disease Activity Score 28 (DAS28). Joint destruction was assessed in the subjects by X-rays of the wrists. Blood samples were collected for assessment of anti-CCP, rheumatoid factor (RF), and erythrocyte sedimentation rate. Forty-eight (23.0%) males and 160 (76.9%) females were included in this study. RF, DAS28, and joint destruction were significantly different between patients with and without anti-CCP (P < 0.0001). DAS28, duration of disease, hospitalizations, and occupation differed significantly between patients with and without joint destruction (P < 0.0001). This study indicates that anti-CCP is correlated with a high disease activity index and more joint destruction in RA patients and it may be used as a prognostic factor for RA.

A Study on the Importance of Anti Cyclic Cytrullinated Peptide Antibodies (Anti-CCP) and Rheumatoid Factor (RF) Assay in Detection of Patients with Rheumatoid Arthritis in North Eastern Part of India

<i>Objective:</i> Rheumatoid arthritis (RA) is a polyarticular and systemic chronic inflammatory autoimmune disease, occurring throughout the world. The aim of the present study is to observe the role of anti-CCP antibody and Rheumatoid Factor (RF) assay in diagnosing patients of rheumatoid arthritis in north-eastern part of India, in the state of Assam and also to evaluate the individual and combined sensitivity and specificity of anti-CCP antibody and RF assay in diagnosing RA. <i>Methods:</i> A total of 88 cases presenting with history of polyarthritis were included in the study of which the study group comprised of 57 clinically diagnosed cases of rheumatoid arthritis and control group comprised of 31 patients of non-RA rheumatic diseases having joint pain. Individual sensitivity and specificity of the above tests, and also the combined specificity of the two tests and also the three tests were calculated and the results of the tests were compared with each other to examine the correlation between them. <i>Results:</i> Sensitivity of anti-CCP ELISA, RF IgM ELISA and RF Latex test was 91.23%, 75.44% and 40.35% with specificity of 70.97%, 67.74% and 90.32% respectively. If the three tests are combined then the combined specificity of the three tests is 99.59%. One important observation was that out of 9 anti-CCP positive cases in the control group(n = 31) 5 cases were weakly positive (titer 6.25 – 20 U/ml), considering cut-off value 6.25 U/ml as mentioned by the kit.If these weakly positive cases in the control group are considered as negative, then specificity of anti-CCP ELISA increases from 70.97% to 87.1% which is more acceptable. <i>Conclusion:</i> From this study it is observed that anti-CCP antibodies are highly sensitive and specific for diagnosing RA. If this test is combined with RF IgM ELISA and Latex test then combined specificity can be increased more than 99%. However, weakly positive titers of anti-CCP antibodies are more prevalent in other non-RA rheumatic diseases in North-Eastern part of India.

Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ +Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ +Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

Anti- Cyclic Citrullinated Peptide Antibodies: Clinical utility and their role as early prognostic markers in Erosive Rheumatoid Arthritis.

Objectives: To assess the diagnosticutilityofanti- cyclic citrullinated protein antibody (anti-CCP) in comparison to rheumatoid factor (RF) in diagnosis of rheumatoid arthritis (RA) and to determine its prognostic value in erosive rheumatoid arthritis.Materials and Methods: The study included 60 patients with clinically suspected RA. Anti-CCPwas measured by enzyme-linked immunosorbent assay (ELISA) and rheumatoid factor (RF) by nephalometry. The seropositivity with RF and ACCP antibodies were studied in comparison with radiographic changes and joint symptoms which included presence and duration of joint involvement- multiple joints, small joints, symmetric joints, stiffness or swelling of joints.Results: Among the 60 patients, the mean age for RA was found to be 43 years. A higher seropositivity was found among the females. The sensitivity and specificity ofanti-CCPreactivity for the diagnosis of RAwere 38.3 and 100 respectively. Among the symptoms studied, small joint involvement and involvement of multiple joints showed a positive association with serologically positive individuals. Patients with high anti-CCP antibody titres showed higher RF titres and severe radiographic erosions.Conclusion: Anti CCP antibodies are a highly specific for rheumatoid arthritis. A combined diagnosis using both high titers ofanti-CCPantibodiesand a positive RF test markedly improvesRAdiagnostic specificity. ACCP antibody detection helps in early diagnosis as well as detection of progressive joint damage.

Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies.

PurposeTo study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) with the ocular manifestations.MethodsThree-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer’s test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests.ResultsSeventy-seven patients (135 eyes, 39%) out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients). The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients). Scleritis was present in 2% of the patients (four patients). Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven patients) had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001.ConclusionOcular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a statistically significant association between the presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular manifestations.

Association between butyrylcholinesterase activity and phenotypes, paraoxonase192 rs662 gene polymorphism and their enzymatic activity with severity of rheumatoid arthritis: Correlation with systemic inflammatory markers and oxidative stress, preliminary report

ObjectivesEvidences indicate that oxidative stress and inflammation are important processes in the development of destructive synovial tissue in rheumatoid arthritis (RA). The two major bioscavenger enzymes that are associated with inflammation and oxidative stress are human-butyrylcholinesterase (BuChE) and paraoxonase-1 (PON-1). Thus, the objective of this study was to determine the relation of BuChE phenotypes and PON-1 Q192R polymorphism with inflammatory markers such as anti-cytroline circulated peptide (CCP)-antibodies, CRP, neopterin, DAS28-CRP in RA patients. Design and methodsIn this study, we examined association of BuChE-phenotypes and activity, PON192rs662 (Q192R) polymorphism and its arylesterase activity (ARE) with systemic-inflammatory-markers and oxidative stress. The present case-control study consisted of 419-RA patients and 398 gender–age-matched unrelated healthy controls from west population of Iran. PON192rs662 polymorphism was detected by real-time-PCR. BuChE phenotype, TAC level, serum BuChE and ARE activities were determined spectrophotometrically. Anti-CCP-antibody and CRP were measured by ELISA and neopterin level was detected by HPLC. We used the EULAR activity criteria to measure DAS28-CRP. ResultsWe found that PON-1-Q192R was associated with severity of RA [remission-to-low and moderate-to-high in dominant Q/Q+Q/R vs. R/R: OR=2.27, p<0.001; codominant Q/Q vs. R/R: OR=1.65, p<0.001 and Q/R vs. R/R: OR=2.12, p=0.003; recessive Q/Q vs. R/R+Q/R: OR=1.79, p=0.032; and allele Q vs. R: OR=1.68, p<0.001] and presence of anti-CCP-antibody (codominant model Q/Q vs. R/R: OR=1.28, p=0.042). The carriers of Q/Q genotype PON-1-Q192R and BuChE non-UU-phenotype had higher ARE activity, serum levels of neopterin, anti-CCP antibody titer and number of tender-joint and lower activity of BuChE and serum level of TAC than that of R/R genotype and BuChE-UU-phenotype. ConclusionsThe current findings demonstrate for the first time that there is a link between systemic inflammatory markers, oxidative stress, the PON192rs662-Q allele and BuChE-non-UU-phenotype and their corresponding enzymatic activity which may be considered as a risk factor for the severity of RA for a population in Iran.

High anti-CCP antibody titres predict good response to rituximab in patients with active rheumatoid arthritis

ObjectivePrevious studies reported that anti-CCP antibody positivity predicts good response to rituximab (RTX) in rheumatoid arthritis (RA). A quantitative approach to such possibility could be a good way to detect the subset of patients most likely to respond. We investigated whether serum anti-CCP antibody titres could predict response to RTX in RA patients. MethodsWe retrospectively investigated RA patients who received RTX. The primary criterion was decrease in DAS28>1.2 at 6months (M6). Secondary efficacy criteria included a good response and remission according to EULAR. Predictors of response were investigated by multivariate logistic regression analysis. ResultsWe included 114 RA patients (81.6% female, median age 53.5 [IQR 45.7–61.2] years, median disease duration 8.5 [4.0–16.0] years). Anti-CCP antibodies were present in 93 patients (81.6%), with median anti-CCP antibody titres 583 [195–1509] U/mL. In all, 44 patients (38.6%) showed decreased DAS28>1.2 at M6. On univariate analysis, high anti-CCP titres were associated with response rather than non-response to RTX (median 1122 [355–1755] vs. 386 [149–800] U/mL, P=0.0191) at M6. On multivariate regression analysis, with a cut-off of 1000 U/mL, anti-CCP antibody titres≥1000 was associated with a decrease in DAS28>1.2 (OR 5.10 [1.97–13.2], P=0.0002); a EULAR good response (4.26 [1.52–11.95], P=0.0059); and a trend for EULAR remission (2.52 [0.78–8.12], P=0.1207). ConclusionHigh anti-CCP antibody titres predict response to RTX in RA. This factor, easily assessed in clinical practice, can help with personalized medicine and selecting the best candidates for RTX treatment.

FRI0081 Titers of Anti-Ccp Antibodies, IL-6, Tnf-Alpha and CRP Are Associated with Increased Carotid Intima-Media Thickness: Cross-Sectional Analysis of A Rheumatoid Arthritis Group without Cardiovascular Risk Factors

BackgroundThe main causes of death in Rheumatoid Arthritis (RA) are cardiovascular events related to early atherosclerosis, myocardial infarction and congestive heart failure. The risk for cardiovascular disease it it not...

Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study.

The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network. We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre. A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality. This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.

Management of Rheumatic Heart Disease in Uganda

Management of Rheumatic Heart Disease in Uganda

Resting energy expenditure is not associated with disease activity in women with rheumatoid arthritis: cross-sectional study.

Background/AimsIncreased resting energy expenditure (REE) in rheumatoid arthritis (RA) patients is thought to be caused by hypermetabolism associated with production of proinflammatory cytokines. Our aim in the present study was to explore the possible association between REE and disease activity in females with RA.MethodsA total of 499 female RA patients were recruited to this cross-sectional study assessing REE scores on disease activity indices (the routine assessment of patient index data 3 [RAPID3], the disease activity score 28, and the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA-associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also enrolled.ResultsREE did not differ between RA patients (all patients, and those in remission or not) and controls, or between RA patients in remission or not (p > 0.05 for all comparisons). Increased REE in total RA patients was associated with younger age and a higher body mass index (BMI) (p < 0.001 and p < 0.001, respectively), but not with disease activity index scores on any of RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of disease duration, functional status, or anti-CCP antibody titer in RA patients was significantly related to REE, based on analysis of covariance.ConclusionsWe found no association between REE and disease activity in RA patients, implying that energy metabolism in RA patients might be independent of RA-associated systemic inflammation.

Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti‐citrullinated peptide antibody titres

Anti-citrullinated protein antibody (ACPA) responses may precede clinical onset of rheumatoid arthritis. Porphyromonas gingivalis peptidylarginine deiminase can citrullinate proteins possibly inducing autoimmunity in susceptible individuals. To determine whether periodontitis, carriage of P. gingivalis, smoking and periodontal therapy influence ACPA titres. Serum and plaque samples were collected from 39 periodontitis patients before and after non-surgical periodontal treatment, and from 36 healthy subjects. Carriage of P. gingivalis was determined by PCR of plaque DNA. ACPA was determined by anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA). Anti-P. gingivalis titres were determined by ELISA. Untreated periodontitis patients had higher anti-CCP antibody titres than healthy controls [three patients (8%) greater than manufacturer suggested assay diagnostic threshold (5 Assay Units/AU) versus none (0%); mean ± SEM: 1.37 ± 0.23 versus 0.40 ± 0.10 AU, p < 0.0001]. Periodontitis patients who smoked demonstrated lower anti-P. gingivalis (15956 ± 4385 versus 2512 ± 1290 Units/ml, p < 0.05), but similar anti-CCP than non-smoking periodontitis patients (smokers: 1.31 ± 0.35; non-smokers: 1.41 ± 0.32 AU). Healthy smokers demonstrated elevated anti-CCP titres (0.75 ± 0.19 AU), at levels between healthy non-smokers (0.15 ± 0.05 AU) and non-smoker periodontitis patients. Six months after periodontal treatment, there were significant reductions in anti-CCP (non-smokers p < 0.05) and anti-P. gingivalis (all participants p < 0.01). In subjects with periodontitis, P. gingivalis infection may be responsible for inducing autoimmune responses that characterize rheumatoid arthritis.

Clinical features and independent predictors in the further development of rheumatoid arthritis in undifferentiated arthritis

This study aims to investigate the prognosis of undifferentiated arthritis (UA) and to estimate the putative predictors contributing to predict the development of UA into rheumatoid arthritis (RA); thus, it could improve appropriate medical intervention. A retrospective cohort study of 218 patients with an initial diagnosis of UA and 2-year follow-up monitoring was carried out. The baseline information including demographic variables, clinical features, and laboratory data was collected. A logistic regression model was used for the statistical analysis. After 2 years of follow-up, 20.18% of UA patients evolved into RA, but 33.03% remained undifferentiated. Meanwhile, 25.23% went into remission, and 21.56% developed into other connective tissue diseases. Univariate and multivariate analysis showed that the titer of antibodies to cyclic citrullinated peptide (anti-CCP), tender joint count and duration of morning stiffness were independent predictors for the development of RA. The area under the curve (AUC) of duration of morning stiffness (0.81) was largest, followed by tender joint count (0.74). The AUC of anti-CCP antibodies (0.68) was higher than that of rheumatoid factor of IgM type (IgM-RF) (0.60), and the combination of these two antibodies was significantly higher than each alone (P < 0.001). In conclusion, UA patients had variable clinical outcomes and prognosis. Only the titer of anti-CCP antibodies, tender joint count, and duration of morning stiffness, instead of IgM-RF, could predict the development of RA. Although the anti-CCP antibody was better than the IgM-RF in predicting RA, a combined detection of them still improved the diagnostic performance.

FRI0032 Increased level of IL-34 in serum and synovial fluid is associated with rheumatoid factor and anti-cyclic citrullinated peptide antibodies titer in patients with rheumatoid arthritis

BackgroundInterleukin-34 (IL-34) is a recently discovered cytokine that binds macrophage colony-stimulating factor (M-CSF). Rheumatoid arthritis (RA) is a representative inflammatory arthritis characterized by increased osteoclastogenesis, which contributes to joint destruction...

AB0484 Anti-CCP profile in rheumatoid arthritis during long-term etanercept treatment

BackgroundAnti-CCP antibody testing is useful in the diagnosis and prognosis of RA. We discuss anti-CCP testing with an emphasis on diagnostic performance and prognostic capability.ObjectivesThere aim of the present study...

AB0301 Characteristics of rheumatoid arthritis patients with adverse effects after the initiation of tocilizumab therapy

BackgroundTocilizumab is a humanized monoclonal antibody that blocks IL-6 mediated pro-inflammatory signalling in rheumatoid arthritis patients. The safety profile of tocilizumab has been extensively evaluated in clinical trials. However, there...

THU0146 Predictive Value of Anti-Cyclic Citrullinated Peptide Antibodies in the Further Development of Rheumatoid Arthritis in Undifferentiated Arthritis

BackgroundUndifferentiated arthritis (UA) is a form of peripheral arthritisthat does not fulfillthe classification criteria for a more definitive diagnosis. It was known that one third of patients with UA progressed...

AB0781 Clinical periodontal disease predicts the future development of chronic inflammatory arthritis.

BackgroundRecent reports suggest the correlation between rheumatoid arthritis (RA) and periodontal disease (PD). However, it is not clear whether PD affects the disease activity of arthritis or the future introduction...