Serum Anti-cyclic Citrullinated Peptide Research Articles

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis.

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response.

Prevalence and clinical significance of serum anti-cyclic citrullinated peptide antibodies in primary Sjögren's syndrome

Objectives: Although anti-cyclic citrullinated peptide (anti-CCP) antibody is a specific marker for rheumatoid arthritis (RA), it is also detected positively in some other rheumatological diseases including Sjögren's syndrome (SS) and even in healthy people. Studies have shown that anti-CCP guides the early diagnosis, prognosis and treatment of RA patients. SS and RA overlap syndrome are common. This study was conducted to determine the prevalence and clinical significance of serum anti-CCP in primary SS patients followed in our outpatient clinic. Methods: Eighty-two primary SS, 100 RA patients and 100 healthy controls applied to rheumatology outpatient clinic were examined. Patients and control groups were compared in terms of demographic characteristics, laboratory results and anti-CCP. Results: In the present study, anti-CCP was positive in 4 (4.9%) of 82 primary SS patients. In the SS group, among other autoantibodies, ANA was found to be positive at 88.8%, RF 45%, SS-A 64.6%, and SS-B 36.7%. There was no relationship between anti-CCP and joint involvement in patients with SS. Conclusions: Anti-CCP antibody positivity can be found in SS patients. Acute phase proteins may be higher in primary SS patients with positive anti-CCP antibody. However, studies have found conflicting findings about the prevalence of erosive arthritis and the future development of RA in these patient groups.

Effect of low dose ionizing radiation versus human wharton’s jelly mesenchymal stem cells in the treatment of experimental rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the major causes of disability that aggrieve a financial burden for the healthcare system as well as for patients. Both stem cell therapy and low-dose radiotherapy (LD-RT) have been recognized as alternative approaches to alleviate pain, inflammation, and bone in the inflamed joints. Accordingly, the present study was designed to compare the efficacy of both modalities in the treatment of RA in experimental rats. Rheumatoid arthritis was induced in forty female rats using Complete Freund’s adjuvant (CFA), divided into four groups (arthritic induction group and three treatment groups) compared to controls: one of the treatment groups received Human’s Wharton Jelly Mesenchymal Stem Cells (WJMSC), and the other two groups received individual doses of 0.5 and 1 Gy of Gamma irradiation once a week for six weeks. After six weeks animals were sacrificed and examined for joint histology, paw swelling, mRNA gene expression for TNF-α, IL-1β and IL-6 together with serum anticyclic citrullinated peptide (anti-CCP) and nitric oxide (NO). Results showed that both doses of (0.5 Gy and 1 Gy) and WJMSC individually modulated RA effects by significantly decreasing the measured biochemical and molecular parameters. However, at the histology level it was evident that irradiation has a better pronounced effect compared to WJMSC, which showed aggravated effects on joint erosion. The present study reports that both IR and WJMSC significantly decreased Anti-CCP, which is a specific marker for RA, however, WJMSC might have deliberate effects on the synovitis and arthritis.

The impact of therapies as monotherapy with combined therapy on novel and traditional biomarkers in patients with rheumatoid arthritis

Background and objectives: Rheumatoid arthritis is an autoimmune and inflammatory disease that influences many tissues and organs. Inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, anti-cyclic citrullinated protein, rheumatoid factor, and 14-3-3η protein have been found to play an important role in both the diagnosis and progression of rheumatoid arthritis. This study aimed to elucidate the effect of anti-rheumatoid medication, as mono- and combined therapy, on these inflammatory mediators. Methods: A cross-sectional study was performed at Hawler Medical University, College of Pharmacy, Erbil, Iraq. Forty-two patients of both genders with rheumatoid arthritis participated in the study as group I. Forty-four age–gender matched adults (with no rheumatoid arthritis) were included as a comparison group or group II. Serum levels of biomarkers were determined by enzyme linked immune sorbent assay. Results: There was a statistically significant (P <0.05) increased level of serum anti-cyclic citrullinated peptide, 14-3-3η protein, erythrocyte sedimentation rate, C-reactive protein, and rheumatic factor levels in group I compared with group II. The serum level of the anti-cyclic citrullinated peptide significantly decreased in rheumatoid patients treated with combined therapy compared with mono remedy. However, the mean of body mass index, age, and gender of group I was non-significantly different from group II (P >0.05). Conclusion: Therapeutic regimen of mono or combined therapy played a role in changing levels of inflammatory markers. Anti-cyclic citrullinated protein significantly decreased with the combined therapy in comparison with the monotherapy regimen. Keywords: Rheumatic arthritis; Monotherapy; Combined therapy; Anti-rheumatoid; Inflammatory markers.

Direct antiviral drugs in the treatment of hepatitis C-infected rheumatoid arthritis Egyptian cohort: safety and clinical impact.

Data about the safety and efficacy of direct-acting antivirals (DAAs) in the treatment of hepatitis C virus (HCV) patients with concomitant rheumatoid arthritis (RA) are scarce. We assessed the impact and safety of DAAs treatment of hepatitis C on rheumatoid arthritis disease activity. Prospectively, we enrolled 65 patients with RA and HCV. A clinico-laboratory evaluation was done at baseline, including liver assessment and RA disease activity score-28 (DAS28). At 12 weeks of post-DAAs treatment, sustained virologic response (SVR12) and DAS28 were reevaluated. The SVR12 was achieved in 59 (90.8%) patients. RA control was achieved in 47 (79.9%) patients. The post SVR12 DAS28 score was significantly lower than the baseline (3.32 ± 0.93 vs. 4.37 ± 0.90; P < 0.001). There was a significant decline in the mean values of serum anticyclic citrullinated peptide, rheumatoid factor, erythrocyte sedimentation rate and C-reactive protein after achieving an SVR12 (30.47 ± 12.37 vs. 57.61 ± 15.91 U/ml; 29.78 ± 19.58 vs. 55.14 ± 16.89 IU/ml; 17.13 ± 10.84 vs. 29.68 ± 14.32 mm/h and 5.76 ± 1.57 vs. 11.44 ± 4.13 mg/l, respectively; P < 0.05). RA activity and antirheumatic drugs were stepped-down [12 (20.3%) and 35 (59.3%) patients showed good and moderate RA response, respectively]. The baseline viral load, absence of cirrhosis and SVR12 were the only predictors of disease control (P < 0.05). No drug-related adverse events or drug-related discontinuation. Unlike interferon, HCV elimination by DAAs significantly improves RA activity and treatment outcome with high safety and efficacy.

The Induction of Autoimmune Arthritis and Sex Differences in Mice Impact the Lung Inflammatory Response to Repetitive Inhalant Organic Dust Extract Exposures

Inflammatory lung diseases are often associated with systemic autoimmunity, and sex differences have been independently described. Men are at increased risk of occupational exposure-associated rheumatoid arthritis (RA) and extra-articular manifestations. Because agriculture work is associated with both chronic lung disease and RA, we sought to determine whether induction of autoimmune arthritis and sex influence airway response to organic dust extract (ODE). Arthritis prone, DBA/1J male and female mice (8 week), were treated daily with ODE or saline for 5 weeks with collagen-induced arthritis (CIA) induced on days 1 and 21. Treatment groups included Sham (saline injection/saline inhalation), CIA (CIA/saline), ODE (saline/ODE); CIA+ODE (CIA/ODE). Bronchoalveolar lavage fluids, lung tissues, serum, and bones were collected. ODE induced airway neutrophil influx, increases in inflammatory mediators (TNF-α, IL-6, CXCL1, CXCL2), release of fibronectin (but not hyaluronan), and increased lung collagen staining as compared to sham. Co-exposure (CIA+ODE) resulted in reduced neutrophil and inflammatory mediator responses as compared to ODE alone, but lung tissue levels of hyaluronan, fibronectin and collagen staining were either augmented or remained increased in CIA+ODE. Arthritis inflammatory scores and serum anti-cyclic citrullinated peptide antibody were greatest in CIA+ODE. Compared to male mice, female mice demonstrated reduced ODE-induced mediator release, hyaluronan and fibronectin as well as lower arthritis scores and serum autoantibody levels with co-exposure. Autoimmune arthritis induction modulates the lung response to inhalant ODE exposure, impacting the inflammatory-interstitial disease process. Congruent with epidemiologic findings, male mice were most susceptible to lung and articular disease resulting from ODE.

A cross-sectional investigation into the association between Porphyromonas gingivalis and autoantibodies to citrullinated proteins in a German population.

Background:Porphyromonas gingivalis (P.g) is unique among pathogens due to its ability to generate citrullinated proteins in an inflammatory milieu, potentially mediating the loss of immune tolerance, the production of anticitrullinated protein antibodies (ACPAs), and subsequently the development of rheumatoid arthritis (RA). Based on this hypothesis, we set out to investigate whether P.g is linked to ACPAs in a well-characterized German population.Participants and methods:A total of 600 participants (292 women and 308 men with a mean age of 67 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam study were selected in 2013, and paired saliva and serum samples were collected. Salivary P.g DNA and serum anticyclic citrullinated peptide (anti-CCP2) levels were quantified by real-time polymerase chain reaction and anti-CCP2 enzyme-linked immunosorbent assay, respectively. In selected participants, additional ACPA fine-specificities were also analysed on a custom-made multiplex peptide array.Results:Among participants with C-reactive protein greater than 3.0 mg/l, a one-unit increase in P.g DNA was associated with an almost twofold increase in anti-CCP2 levels. Moreover, participants with high P.g DNA had on average approximately 2.8-times higher anti-CCP2 levels when compared with participants with low P.g DNA, (Holm-adjusted p value = 0.01). Furthermore, citrullinated epitopes on α-enolase and vimentin were common ACPA reactivities among participants who also had high P.g DNA and elevated C-reactive protein.Conclusions:Our study suggests that in specific subgroups of individuals with systemic inflammation, higher salivary P.g DNA is associated with elevated serum ACPA. These data support a role for P.g in the development of anticitrulline immunity.

Rheumatoid meningitis sine arthritis

Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even after 1 year of follow up. Clinicians should be aware of the possibility of rheumatoid meningitis without rheumatoid arthritis and keep it on the differential for patients with aseptic meningitis and otherwise negative work up.

Factors influencing spinal sagittal balance, bone mineral density, and Oswestry Disability Index outcome measures in patients with rheumatoid arthritis.

To identify the factors influencing spinal sagittal alignment, bone mineral density (BMD), and Oswestry Disability Index (ODI) outcome measures in patients with rheumatoid arthritis (RA). We enrolled 272 RA patients to identify the factors influencing sagittal vertical axis (SVA). Out of this, 220 had evaluation of bone mineral density (BMD) and vertebral deformity (VD) on the sagittal plane; 183 completed the ODI questionnaire. We collected data regarding RA-associated clinical parameters and standing lateral X-ray images via an ODI questionnaire from April to December 2012 at a single center. Patients with a history of spinal surgery or any missing clinical data were excluded. Clinical parameters included age, sex, body mass index, RA disease duration, disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR), serum anti-cyclic citrullinated peptide antibody, serum rheumatoid factor, serum matrix metalloproteinase-3, BMD and treatment type at survey, such as methotrexate (MTX), biological disease-modifying anti-rheumatic drugs, and glucocorticoids. We measured radiological parameters including pelvic incidence (PI), lumbar lordosis (LL), and SVA. We statistically identified the factors influencing SVA, BMD, VD, and ODI using multivariate regression analysis. Multivariate regression analysis showed that larger SVA correlated with older age, higher DAS28-ESR, MTX nonuse, and glucocorticoid use. Lower BMD was associated with female, older age, higher DAS28-ESR, and MTX nonuse. VD was associated with older age, longer disease duration, lower BMD, and glucocorticoid use. Worse ODI correlated with older age, larger PI-LL mismatch or larger SVA, higher DAS28-ESR, and glucocorticoid use. In managing low back pain and spinal sagittal alignment in RA patients, RA-related clinical factors and the treatment type should be taken into consideration.

Study on the effect and predictive to bronchiectasis combined with rheumatoid arthritis

Objective: To explore the clinical characteristics of bronchiectasis(BR)coexisting in patients with rheumatoid arthritis (RA). Methods: One hundred and forty-eight bronchiectasis patients were retrospectively analyzed. These cases were all diagnosed in the Respiratory Department of Shanghai Pulmonary Hospital and Shanghai Gongli Hospital of Pudong New Area during Jan. 2012 to Dec.2015.The patients consisted of 74 males and 74 females, aging from 45 to 79 [mean(65±11)] years. In these patients, coexisting rheumatoid arthritis was found in 34 males and 36 females, aging from 45 to 79[mean(68±12)] years(RA-BR group). Patients with bronchiectasis alone consisted of 40 males and 38 females, aging from 49 to 76 [mean(63±10)] years (BR alone group). Data between the 2 groups of patients were compared, including general clinical features, serum anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), chest high-resolution CT (HRCT), and lung function . FACED scores were used to assess the severity of bronchiectasis. Meanwhile, we analyzed the correlation between anti-CCP and FACED scores in the 2 groups. Results: We observed an increase of serum anti-CCP in RA-BR patients compared with BR alone patients (196±68 versus 64±26, P<0.05). In addition, FACED scores in RA-BR patients were higher than those in BR patients (5.2±1.8 versus 3.1±1.4 , P< 0.05). Positive correlations between serum anti-CCP levels and FACED scores (r=0.678, r=0.461, P<0.05) in both RA-BR and BR alone groups were observed in this study. Conclusions: The disease severity scores of RA-BR patients were higher than those of patients with BR alone. Levels of serum anti-CCP may act as a predictor for the diagnosis and prognosis of bronchiectasis in patients with RA.

Synovial IL-21/TNF-producing CD4+ T cells induce joint destruction in rheumatoid arthritis by inducing matrix metalloproteinase production by fibroblast-like synoviocytes.

Bone and cartilage destruction is one of the key manifestations of rheumatoid arthritis (RA). Although the role of T helper (Th)17 cells in these processes is clear, the role of IL-21-producing cells T cells has been neglected. We sought to investigate the role of IL-21 in RA by focusing on the functional characteristics of the main producers of this cytokine, synovial CD4+IL-21+ T cells. We show that the frequency of both synovial fluid (SF) CD4+IL-21+ or CD4+IL-21+TNF+ T cells in patients with RA was significantly higher compared with patients with psoriatic arthritis (PsA). The frequency of peripheral blood (PB) IL-21+CD4+ T cells in patients with RA positively correlated with disease activity score 28 (DAS28), serum anticyclic citrullinated peptide (anti-CCP) antibodies and IgM-rheumatoid factor (IgM-RF). IL-21 levels in RA SF were associated with matrix metalloproteinase (MMP)-1 and MMP-3. Related to this, IL-21 induced significantly the secretion of MMP-1 and MMP-3 in RA synovial biopsies. Sorted SF CD4+IL-21+ T cells significantly induced the release of MMP-1 and MMP-3 by fibroblast-like synoviocytes (FLS) compared with medium or CD4+IL-21- T cells in a coculture system. Neutralization of both IL-21 and TNF resulted in significantly less production of MMP by FLS. The results of this study indicate a new role for synovial CD4+IL-21+TNF+ T cells in promoting synovial inflammation/joint destruction in patients with RA. Importantly, IL-21 blockade in combination with anti-TNF might be an effective therapy in patients with RA by inhibiting MMP-induced inflammation/joint destruction.

The amount of citrullinated proteins in synovial tissue is related to serum anti-cyclic citrullinated peptide (anti-CCP) antibody levels.

The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes. Patients with high amount of citrullinated proteins in synovial tissue (3 out of 7) have high levels of anti-CCP in serum. However, in the remaining 4 patients, the amount of synovial citrullinated proteins was minimal and their sera showed low levels of anti-CCP antibodies. Furthermore, we observed an increase in PADI2 mRNA expression in RA synovial tissue compared with OA patients (p = 0.02). We detected PADI3 mRNA in the synovial tissue of RA patients, but not in the tissue of OA patients. Even though fibroblast-type synoviocytes in RA are not the main source of PADs in the synovial tissue, they express PADI2 mRNA moderately, PADI4 mRNA weakly, while there is no detectable expression of PADI3 mRNA. In conclusion, we found a variety of citrullinated proteins in the synovial tissue of RA patients and the amount of such proteins is related to serum concentration of anti-CCP antibodies. We identified the presence ofPADI3 mRNA expression in synovial tissue and PADI2 and PADI4 mRNA expressions in fibroblast-like synoviocytes from patients with RA.

SUBCLINICAL INTERSTITIAL PULMONARY INJURY IN RHEUMATOID ARTHRITIS

Subjects and methods. The study enrolled 61 inpatients diagnosed with RA (according to the 1987 American College of Rheumatology criteria) who were treated at the V.A. Nasonova Research Institute of Rheumatology; in so doing, high-resolution computed tomography revealed lung changes as a ground glass pattern in 15 patients, reticular striation, traction bronchoectases, and lung tissue changes as honeycomb ones in 25 patients; no lung abnormalities were found in 21 patients. DAS28 was applied to determine the inflammatory activity of RA. The RA patients underwent X-ray studies of the hand, foot, and chest, by using accordingly X-Ray unit and spiral computed tomography scanner (section thickness, 0.65 mm). External respiration function (ERF) indicators were studied with plethysmograph. IgM rheumatoid factor was measured using an immune nephelometer. Serum anti-cyclic citrullinated peptide antibodies were assayed by immunochemiluminescence technique on a Cobas e411 analyzer. The xMAP technology using a BioPlex200 analyzer was employed to determine the serum concentrations of 27 cytokines in 15 patients with subclinical IPI and in 25 with clinical IPI. Results and discussion. The major respiratory signs in patients with IPI proved to be cough (24 %), expectoration (20 %), dyspnea (16 %), and crepitation (64 %) on auscultation. Three patients with subclinical IPI were found to have crepitation on auscultation. Respiratory symptoms were absent in the RA patients without IPI. It should be noted that there are a larger number of RA patients with a high smoking index among the RA patients with IPI than among those without IPI (p &lt; 0.05). Investigation of ERF indicators revealed a statistically significantly lower lung diffusing capacity (LDC) in the RA patients with subclinical IPI than in those without IPI (p &lt; 0.05). Other ERF indicators showed no significant deviations of the reference values. LDC and total lung capacity appeared to be statistically significantly lower in the RA patients with clinical IPI than in those without IPI (p &lt; 0.005 and p &lt; 0.05, respectively). The differences in LDC failed to reach the statistical significance in the RA patients with subclinical IPI and in those with clinical IPI. Examination of cytokine concentrations revealed a tendency towards the higher levels of interleukin-7 (IL-7), IL-12, IL-13, IL-15, IL-17, and platelet-derived growth factor BB in the RA patients with subclinical IPI than in those with clinical IPI. At the same time, the differences in the concentration of vascular endothelial growth factor (VEGF) turned out to be statistically significant (p &lt; 0.05). Moreover, the levels of IL-10, interferon-γ, and RANTES proved to be significantly higher in the patients with clinical IPI than in those with subclinical IPI (p &lt; 0.008; p &lt; 0.0003, and p &lt; 0.03, respectively). Conclusion. Thus, the problem associated with the early diagnosis and timely adequate treatment of IPI in patients with RA is relevant. The preclinical form of IPI in patients with RA is associated with ground glass radiological and tomographic patterns and lower LDC values. VEGF may lay a claim to the role of a predictor of pulmonary fibrosis in the RA patients with subclinical IPI.

Anti-cyclic citrullinated Peptide antibody is associated with interstitial lung disease in patients with rheumatoid arthritis.

ObjectivePatients with rheumatoid arthritis (RA) are at risk to develop RA-associated interstitial lung disease (RA-ILD). This retrospective study aimed to investigate the potential association of the positivity of serum anti-cyclic citrullinated peptide antibody (anti-CCP2) and rheumatoid factor (RF) with RA-ILD in RA patients.MethodsA total of 285 RA patients were recruited at the inpatient service of Peking Union Medical College Hospital in China between 2004 and 2013. Individual patients were evaluated for the evidence of ILD. The concentrations of serum anti-CCP2 and RF in individual patients were measured. The potential risk factors for ILD in RA patients were assessed by univariate and multivariate models.ResultsThere were 71 RA patients with RA-ILD, accounting for 24.9% in this population. The positive rates of anti-CCP2 and RF in the patients with RA-ILD were significantly higher than that in the patients with RA-only (88.7% vs. 67.3%, p<0.001; 84.5% vs. 70.6%, p = 0.02, respectively). Univariate and multivariate logistic regression analysis revealed that RA patients with positive serum anti-CCP2, but not RF, were associated with an increased risk of ILD (crude odds ratio [cOR] 3.83, 95% confidence interval [CI] 1.74–8.43, p<0.001; adjusted odds ratio [aOR] 3.50, 95% CI 1.52–8.04, p<0.001).ConclusionOur findings suggest that positive serum anti-CCP2, but not RF, may be associated with RA-ILD in RA patients.

Serum interleukin-17 levels and rheumatoid arthritis patients with bone and joint damage

Objective To observe the correlation between serum interleukin (IL)-17 levels with bone and joint damage in rheumatoid arthritis (RA) patients and the possible mechanism.Methods Fifty-five cases of RA in our hospital were selected as the observation group during the period from October 2010 to June 2013,and 55 healthy volunteers were selected as the control group simultaneously.The serum IL-17 and anti-cyclic citrullinated peptide antibody (anti-CCP) levels were detected by double antibody sandwich enzyme linked immunosorbent assay (ELISA).The serum IL-17 levels in RA patients with different stages of X-ray were compared.The relationship between serum IL-17 levels with active phase,rheumatoid factor and morning stiffness was observed.Results The serum IL-17 levels [(308.42 ±76.14) ng/L] and anti-CCP levels [(1 325.3 ±234.1) AU/ml] in the observation group were significantly higher than those of the control group (P ＜0.05).There was significant difference in the serum IL-17 levels among different stages of X-ray.The higher the stages of X-ray,the higher the levels of serum IL-17 [the serum IL-17 levels at stage Ⅰ,Ⅱand Ⅲ:[(208.23 ±67.41),(322.62 ±78.35),(452.81 ±88.32) ng/L,P＜0.05].The serum IL-17 levels at the active phase [(342.61 ± 101.41) ng/L] were significantly higher than those of the patients at the non-active period [(228.61 ± 101.54) ng/L].The serum IL-17 levels in patients positive for serum rheumatoid factor [(318.74 ±98.42) ng/L] were higher than those of the patients negative for serum rheumatoid factor-negative [(220.56 ± 99.62) ng/L].The serum IL-17 levels were significantly higher in patients with long duration of morning stiffness [(356.27 ± 88.74) ng/L] than those in patients with a short duration of morning stiffness [(201.38 ± 78.43) ng/L,P ＜ 0.05].Conclusion Serum IL-17 plays an important role in the development of RA.Patients with severe bone and joint damage have high serum IL-17 levels. Key words: Interleukin-17; Rheumatoid arthritis; Bone and joint damage

Assessment of Interleukin‐6 Receptor Inhibition Therapy on Periodontal Condition in Patients With Rheumatoid Arthritis and Chronic Periodontitis

Overproduction of interleukin (IL)-6 may play a pathologic role in rheumatoid arthritis (RA) and chronic periodontitis (CP). The present study assesses IL-6 receptor (IL-6R) inhibition therapy on the periodontal condition of patients with RA and CP. The study participants were 28 patients with RA and CP during treatment with IL-6R inhibitor, and 27 patients with RA and CP during treatment without IL-6R inhibitor. Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers and immunoglobulin G against periodontopathic bacteria were examined after medication with IL-6R inhibitor for 20.3 months on average (T1) and again 8 weeks later (T2). No differences were observed between the groups in any parameter values at T1, except for serum IL-6 levels. The anti-IL-6R group showed a significantly greater decrease in gingival index, bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and serum levels of IL-6 and matrix metalloproteinase (MMP)-3 from T1 to T2 than the control group (P <0.05). A significant correlation was found between changes in serum anticyclic citrullinated peptide levels and those in PD and CAL in the anti-IL-6R group (P <0.05), whereas both groups exhibited a significant association between changes in serum MMP-3 levels and those in BOP (P <0.05). Changes in periodontal and serum parameter values were different between the patients with RA and CP during treatment with and without IL-6R inhibitor.

Significance of serum anti-cyclic citrullinated peptide antibodies in diagnosis of juvenile idiopathic arthritis

Objective To investigate the clinical significance of serum anti-cyclic citrullinated peptide(anti-CCP) antibodies in diagnosis of juvenile idiopathic arthritis(JIA). Methods Serum anti-CCP antibodies of 68 children suspected of JIA with fever and arthritis of unknown causes were determined by ELISA,and comprehensive analysis was carried out with clinical data and related laboratory findings. Results Among the 68 children suspected of JIA,there were 10 cases of polyarticular JIA,13 cases of systemic onset JIA,8 cases of oligoarticular JIA and 13 cases of enthesitis related JIA.There were 11 cases of other rheumatoid diseases,8 cases of neoplastic diseases of blood and 5 cases of infectious diseases.The serum anti-CCP level in children suspected of polyarticular JIA was significantly higher than those in children suspected of systemic onset JIA,oligoarticular JIA and enthesitis related JIA(P0.05).With serum anti-CCP ≥15.8 RU/mL as the positive threshold value,the area under receiver operating characteristic curve was 0.80,and the sensitivity and specificity in diagnosis of polyarticular JIA were 80% and 67.6% respectively.The serum anti-CCP level was positively related to serum C-reaction protein level in children suspected of polyarticular JIA(r=0.764,P=0.017). Conclusion Serum anti-CCP can be used for the diagnosis of polyarticular JIA,and 15.8 RU/mL may be a suitable cut-off level.

Is serum anti-cyclic citrullinated peptide level useful in the diagnosis of rheumatoid arthritis?

BackgroundTo find out whether serum level of anti-cyclic citrullinated peptides (anti-CCP) could be useful in the diagnosis of rheumatoid arthritis (RA). MethodsThe study was performed against 1972 patients who visited Hanyang University Medical Center and were tested positive for anti-CCP. ResultsWhen test results were classified into 6 groups according to the anti-CCP level, diagnostic rates of RA in each group were distributed from 73.6% to 77.2%. The increase of serum level did not have any correlation with the diagnostic rate of RA. ConclusionsThe level of serum anti-CCP was not useful in the diagnosis of RA.

Serum anti-cyclic citrullinated peptide antibodies may predict disease activity in rheumatoid arthritis

To define the relationship between serum anti-cyclic citrullinated peptide antibodies (anti-CCP) and disease activity, and to construct a new disease activity index by using anti-CCP in rheumatoid arthritis (RA). One hundred and five RA patients were included. Disease activity based on DAS28-ESR and serum anti-CCP was measured. There was correlation between serum anti-CCP and DAS28-ESR. (R (2) = 0.71, P value < 0.01). New disease activity index was developed by replacing anti-CCP with ESR in DAS28-ESR. There was correlation between new model and DAS28-ESR. (R (2) = 0.91, P value < 0.01) The new composite index best cut-off values corresponding to DAS28-ESR values of 2.6, 3.2, and 5.1 were 3.21, 3.38, and 4.74, respectively. There was agreement between new model and DAS28-ESR for determination of patients in different disease activity categories. (Kappa = 0.71, P value < 0.01). The new disease activity index that applies serum anti-CCP may predict disease activity in RA.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor sera titers in leprosy patients from Mexico

Leprosy offers a broad spectrum of altered immunological sceneries, ranging from strong cell-mediated immune responses seen in tuberculoid leprosy (TT), through borderline leprosy (BB), to the virtual absence of T cell responses characteristic in lepromatous leprosy (LL). The exact mechanism of autoantibodies production remains unknown in leprosy and other chronic inflammatory diseases and also the contribution of these antibodies to the pathogenesis of the disease. The aim of this study is to evaluate the frequency and profiles of serum anti-cyclic citrullinated peptide antibodies (a-CCP), rheumatoid factor (RF) and its relationship with leprosy spectrum. Serum samples from 67 leprosy patients (54 LL, 5 TT and 8 BB) and 46 clinically healthy subjects (CHS) from the same endemic region were investigated. The clinical chart and questionnaire were used to obtain clinical information. Anti-cyclic citrullinated peptide antibodies (a-CCP) were measured by enzyme-linked immunosorbent assay, whereas the rheumatoid factor (RF) levels were measured by nephelometric method. The mean age of patients was 51.5 ± 13 years. Sera levels of a-CCP where higher in leprosy patients than in CHS (5.9 ± 11.6 vs. 0.3 ± 0.29) (P < 0.0001); the same pattern was found for RF sera titers without reaching statistical significance (16.8 ± 22.5 vs. 9.9 ± 3) (P = NS). We did not find a correlation between a-CCP and RF Rho =0.02786 (IC 95%) P = 0.8229. However, LL patients had higher a-CCP and RF levels than TT patients. Although an absence in correlation was observed, the serum levels of a-CCP antibodies and RF appeared to be useful in distinguishing LL from TT patients with a limited significance in detecting reactional leprosy patients.