anti-CCP Antibody Titers Research Articles

Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis

HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy.

The prognostic value of 99m Tc-glucosamine imaging in patients with rheumatoid arthritis: a single center prospective study.

Poor prognostic factors in rheumatoid arthritis (RA) are associated with a more severe form of the disease. Nuclear medicine functional imaging has shown remarkable merit at identifying active disease in patients with RA and is increasingly being used in this regard. However, its prognostic value has not been evaluated thoroughly. We aimed to assess the prognostic value of technetium-99m ( 99m Tc-) glucosamine imaging in patients with RA. Twenty-two participants diagnosed by an experienced rheumatologist with RA were recruited for inclusion in the study. Blood samples were obtained from each participant for baseline C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody titer. On the same day, each participant was injected with 20-25 millicurie (mCi) of 99m Tc-glucosamine. Planar and single-photon emission computed tomography images of known disease sites were acquired up to 2 hours after radiopharmaceutical administration. Affected joints were qualitatively assessed and graded for 99m Tc-glucosamine uptake and compared with blood results. All participants affected joints had an increased uptake of the radiopharmaceutical, with 14 (63.6%) having elevated RF and anti-CCP antibody titers. Eight of the 14 patients with increased RF and anti-CCP antibodies had grade 3 uptake of 99m Tc-glucosamine. The remaining 6 had grade 2 uptake. A significant correlation between higher grade uptake and increased levels of RF and anti-CCP antibodies ( P = 0.031) was observed. We found a strong correlation between high-grade disease on imaging and the presence of RF and anti-CCP antibodies in patients with RA.

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.

Anti-CCP antibody in rheumatoid arthritis patients and its relation with severity of the disease

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic and erosive polyarthritis causing irreversible joint disability. It is the most common persistent inflammatory arthritis, affecting from 0.5 to 1% of the general population worldwide. Antibodies to citrullinated proteins (anti-CCP antibody) have been described in patients with RA and these appear to be the most specific marker of the disease. Methods: This cross-sectional study was carried out at department of medicine, Sher-E-Bangla Medical College Hospital, Barisal Form July’ 2016 to December’ 2016. All rheumatoid arthritis patients attending at OPD and those got admitted under Medicine Dept, who was satisfying the inclusion and exclusion criteria were included consecutively and purposively in this study. Results: Total 70 cases were included; the mean age was found 46.57±13.10 years in anti-CCP antibody positive group and 44.19±11.21 years in anti-CCP antibody negative group. Female were predominant in both groups. Duration of disease was around 8 years in both groups. Mean ESR was 29.0±22.0 mm in anti-CCP antibody positive group and 12.25±10.6 mm in anti-CCP antibody negative group. Mean rheumatoid factor was 189.4±102.1 U/L in anti-CCP antibody positive group and 66.5±36.0 U/L in anti-CCP antibody negative group. Mean DAS 28 score was 4.6±1.4 and 3.6±1.3 in anti-CCP antibody positive and negative group respectively. The mean difference was statistically significant (p<0.05) between the groups. Patients in disease remission had lower anti-CCP antibody titer than those with low, moderate or high disease activity. Significantly positive correlation (r=0.596; p=0.001) between severity of rheumatoid arthritis and anti CCP antibody level was observed. Conclusion: In RA patients’ disease was more severe in anti-CCP antibody positive group and significantly positive correlation between anti-CCP antibody level with disease severity of RA was observed. BIRDEM Med J 2022; 12(1): 36-40

A Closer Look at the Role of Anti-CCP Antibodies in the Pathogenesis of Rheumatoid Arthritis-Associated Interstitial Lung Disease and Bronchiectasis.

Rheumatoid arthritis (RA) is an articular disease with extra-articular manifestations. Pulmonary manifestations are not uncommon and can involve all compartments of the lungs with airway disease in the form of bronchiectasis or bronchiolitis, interstitial lung disease (ILD), pleural effusions and parenchymal lung nodules. The pulmonary features may present synchronously or after the articular disease, but, importantly, it may be the first presentation in 10% of patients in the absence of articular symptoms. Here we discuss the pathogenesis of RA lung involvement, particularly interstitial lung disease and bronchiectasis, focusing on the role anti-CCP antibodies (ACPAs). We highlight the complex interplay among genetic, environmental and immune factors. Furthermore, we explore the relationship of citrullination and smoking as well as the concept of interstitial pneumonia with autoimmune features (IPAF), where patients do not have evidence of another known cause of interstitial pneumonia and have incomplete features of connective tissue disease (CTD). We surmise that the frequency and titers of rheumatoid factor (RF) and ACPAs are increased in bronchiectasis and RA-bronchiectasis compared to RA patients without lung disease. ACPA is associated with more severe disease in both RA-ILD and RA-bronchiectasis even in the absence of articular symptoms. There is no clear prediction of development of articular RA with high ACPA levels in the context of positive ACPA and ILD; however, in RA-bronchiectasis, patients with positive antibodies can develop RA within a year after diagnosis of bronchiectasis. Though the primary focus of this narrative is to highlight the role of ACPA in pathogenesis and clinical practice, we also discuss the current treatment options and trials in RA-ILD and RA-bronchiectasis. Currently, there are no clear treatment guidelines. The treatments are now focusing on using a combination of immunosuppression and antifibrotic agents. Combination treatment targets both the fibrotic and inflammatory components of the disease process. Further studies are needed to identify the use of ACPA as a biomarker to tailor the treatment in RA-ILD and RA-bronchiectasis.

POS0482 WOOD SMOKE EXPOSURE IS ASSOCIATED WITH HIGHER ANTI-CCP ANTIBODY TITERS IN HISPANIC PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Wood smoke exposure is a risk factor for the development of chronic obstructive pulmonary disease (COPD), lung cancer and cardiovascular disease and it has also been linked to higher anti-CCP antibodies in patients with rheumatoid arthritis (RA) and COPD (1).Objectives:The objective of the present study is to report the correlation between anti-CCP, IgG, IgM and IgA rheumatoid factor (RF) to wood smoke exposure in patients with RA. Additionally, evaluate the impact of disease activity, biomass exposure, and disease duration on anti-CCP antibody levels.Methods:A cross-sectional, observational study was designed based on a cohort of Hispanic RA patients. All fulfilled the 2010 ACR/EULAR classification criteria for RA. Biomass smoke exposure was expressed using the biomass exposure index (BEI) calculated from the mean of exposed hours per day multiplied by the number of years exposed. Subjects were divided into two groups: those exposed to wood smoke with BEI ≥1 and subjects not exposed to wood smoke. They were matched by age, gender, and comorbidities. Anti-CCP antibodies and RF were measured by ELISA with cutoff points of <5 U/mL and <20 U/mL respectively.Results:A total of 318 subjects were included, 159 (50%) of them had a history of exposure to wood smoke. Anti-CCP antibody positivity was present in 102 (64.2%) with a median titer of 97.1 U/mL (1.7-198) in the RA exposed group, and in 89 (56%) with a median titer of 8.5 U/mL (1.1-145) in the RA non-exposed group. A significant difference was found in anti-CCP antibody titers between groups (p=0.003). (Table 1). Spearman’s rho showed a small but statistically significant correlation between BEI and anti-CCP antibody titers (rho= 0.170, p=0.002). Biomass exposure was independently related to higher anti-CCP antibody titers (B=35.4, p<0.001).Conclusion:RA patients who were exposed to wood smoke had higher titers of anti-CCP antibodies than non-exposed RA patients. Furthermore, biomass exposure was shown to be independently related to higher titers of anti-CCP antibodies.

Characteristics of rheumatoid arthritis with immunodeficiency-associated lymphoproliferative disorders to regress spontaneously by the withdrawal of methotrexate and their clinical course: A retrospective, multicenter, case-control study.

To investigate clinical characteristics and time course of lymphoproliferative disorders (LPDs) in rheumatoid arthritis (RA) patients after methotrexate (MTX) discontinuation, in those who achieved spontaneous regression (SR). We retrospectively reviewed clinical data from RA patients with LPDs obtained from eight institutions between 2000 and 2017 and compared clinical and pathological findings between SR and non-SR groups. Among 232 RA patients with LPDs, 216 were treated with MTX at the onset of LPD and 144 (66.7%) achieved SR after MTX discontinuation. Higher MTX doses, high titers of anti-CCP antibodies (>13.5 U/mL), and lower LDH and soluble IL-2 receptor levels were associated with SR. Lymphocyte count was decreased at LPD onset and increased at 2 weeks after MTX discontinuation in the SR group. Epstein-Barr virus-positive mucocutaneous ulcer, reactive lymphoid hyperplasia and unclassifiable B-cell lymphoma, were more frequent in the SR than in the non-SR group. In multivariable analysis, diffuse large B-cell lymphomas was an independent predictive factor for non-SR. In the patients with SR, 73.9% achieved partial or complete regression as early as 2 weeks after MTX discontinuation. SR and non-SR in RA patients with LPDs after MTX discontinuation were associated with certain clinical characteristics.

Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive connective tissue disease: a retrospective observational study including information on the HLA-DRB1 allele and citrullination dependency

BackgroundThe anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD.MethodsIn total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients.ResultsTwo out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency.ConclusionsAnti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD.

Differential regulation and correlation between galectin-9 and anti-CCP antibody (ACPA) in rheumatoid arthritis patients

BackgroundGalectin-9 (Gal-9) is involved in the regulatory process of immune responses or inflammation. The aim of the present study is to characterize circulating Gal-9 in patients with rheumatoid arthritis (RA) and its relationship with RA disease activity and phenotype.MethodsA total of 116 RA patients and 31 age-matched healthy controls were included in this study. Disease activity of RA patients was determined by Disease Activity Score of 28 joint scoring system (DAS28-ESR). Levels of Gal-9 in serum were determined by enzyme-linked immunosorbent assay (ELISA).ResultsSerum levels of Gal-9 were significantly higher in patients with RA compared to those in controls (median 7577 pg/ml [interquartile range (IQR) 5570–10,201] versus 4738 pg/ml [IQR 4267–5630], p = 0.001). There were significant differences in serum Gal-9 between RA patients with and without RA-ILD (9606 pg/ml [IQR 8522–12,167] versus 7078 pg/ml [IQR 5225–9447], p < 0.001) or those with and without advanced joint damage (stage II–IV, 9606 pg/ml [IQR 8522–12,167] versus 7078 pg/ml [IQR 5225–9447], p < 0.001). Although serum levels of Gal-9 correlated with the titers of ACPA (r = 0.275, p = 0.002), levels of ACPA titers conferred the different relationship, between serum Gal-9 and inflammatory mediators or RA disease activity. Although Gal-9 was correlated with ACPA titers (r = 0.508, p = 0.002), there was no correlation between Gal-9 levels and erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3 (MMP-3), or DAS28-ESR in RA patients with high titers of ACPA (> 200 U/ml). Conversely, Gal-9 was correlated with MMP-3 (r = 0.300, p = 0.007) or DAS28-ESR (r = 0.331, p = 0.004) but not with ACPA titer in RA patients with low titers of ACPA titers (< 200 U/ml).ConclusionsSerum levels of Gal-9 were increased in RA patients and associated with RA disease activity in RA patients without high titers of ACPA. The levels of ACPA titers may influence the values of circulating Gal-9 in RA patients with various clinical phenotypes. These data suggest that Gal-9 possessed the properties of pro-inflammatory or arthropathic biomarker under the status of ACPA titers.

Anti-Cyclic Citrullinated Peptide Antibody as a Predictor of Rheumathoid Arthritis Complications.

Introduction:Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, with more frequent occurrence in the female gender, it primarily affects the lining of the synovial joints, and is associated with lower quality of life, inability to work, progressive disability, and all of these patients are more likely to develop other comorbidities.Aim:To display the role of anti-cyclic citrullinated peptide antibody (anti-CCP) in evaluating RA complications during a one-year follow-up, and compare its values with values of rheumatoid factor (RF).Methods:The study included 40 patients with RA, out of which 6 were excluded during the 1-year follow-up. All patients were treated with anti-rheumatics, methothrexate 15-25mg, occasionally corticosteroids at the same doses.Results:Anti-CCP values were also significantly higher during the second examination and were 5.0 ± 1.9 (range 0.5-7.6) compared to the first examination when they were 4.2 ± 1.3 (range 0.4-6.2) indicating a higher sensitivity of Anti-CCP in detecting of disease progression (t = -2.064; p = 0.043). Anti-CCP values were statistically significant in patients with complications compared to those without during the first examination and at follow-up after one year (t = 5,382; p = 0.0001).Conclusion:The positivity of anti-CCP antibodies is a useful marker in terms of predicting the course and prognosis of the RA. A higher titer of anti-CCP antibodies represents a poorer prognosis for the disease. Determination of the presence of anti-CCP antibodies should be performed as a routine examination in all patients with suspected rheumatoid arthritis.

A novel mutation in NCF2 resulting in very-early-onset colitis and juvenile idiopathic arthritis in a patient with chronic granulomatous disease

BackgroundChronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The disease primarily presents with recurrent infections, and patients may also present with inflammatory conditions, including noninfectious colitis, and an increased frequency of autoimmunity. We report here a patient with CGD in whom the presentation, unlike the classical presentation of CGD, was predominantly of an inflammatory and autoimmune phenotype.Case presentationA 3-year-old Pakistani female presented with bloody diarrhea since the age of 7 days, followed by the development of perianal abscesses and fistula. There was no other history of recurrent infections. The patient subsequently developed joint pain and stiffness with persistently elevated inflammatory markers and elevated anti-cyclic citrullinate peptide (anti-CCP) antibody titer. She was diagnosed with oligoarticular juvenile idiopathic arthritis and colitis. The diagnosis of CGD was later made and was based on the absence of NADPH oxidase activity in the patient’s neutrophils upon phorbol myristate acetate (PMA) stimulation using the dihydrorhodamine-1,2,3 (DHR) flow cytometry test. Targeted next-generation sequencing revealed an unreported deletion mutation in exon 10 as a homozygous loss-of-function variant of the human neutrophil oxidase factor 2 (NCF2) (NCF2: NM_001190789, nucleotide change: c.855_856del:p.T285fs). The gene encodes a protein subunit, p67phox, in the NADPH enzyme complex.ConclusionsThe case emphasizes the importance of maintaining high clinical suspicion of immunodeficiency and CGD in patients with very-early-onset colitis and autoimmune disorders. This case is important due to its rarity and because it might represent a previously undiscovered mutation, which is possibly more common in the patient’s ethnic group. Other mutations in NCF2 have been linked to inflammatory bowel disease and autoimmunity, but without CGD, suggesting similarities in the pathogenesis.

Anti-cyclic citrullinated peptide antibody titers decrease in rheumatoid arthritis patients treated with tocilizumab: A pilot study

Objectives: To analyze the effects of tocilizumab on peripheral B-cell subpopulation and its ability to produce anti-cyclic citrullinated peptide (CCP) antibody in patients with rheumatoid arthritis (RA).Methods: Thirteen consecutive RA patients initiated with tocilizumab were enrolled in our prospective study. Anti-CCP antibody titers and clinical parameters were evaluated during treatment. Peripheral blood B-cell subsets were analyzed using flow cytometry according to the Human Immunology Project.Results: Disease activity was significantly improved and anti-CCP antibody titers significantly decreased at week 24 compared to baseline. The percentages of post-switch memory B cells in CD19+ cells transiently increased at week 12, but there was no significant difference in any of the investigated B-cell subpopulations at week 24 compared to baseline. The ratios of post-switch memory to naïve B cells (post-switch/naïve) correlated negatively with anti-CCP antibody titers regardless of the time-points.Conclusion: Our study indicated that tocilizumab has a potential to reduce anti-CCP antibody production presumably by affecting post-switch/naïve ratio, and that anti-CCP antibody titers reflect B-cell distribution/subpopulation. As anti-CCP antibodies are produced in lymph nodes or ectopic lymphoid structures in synovial tissues, not in circulation, transient increment of post-switch memory B cells after tocilizumab treatment may reflect the altered balance of B-cell distribution between circulation and arthritic joints, resulting in suppressed production of anti-CCP antibody in situ.

Elevated anti-cyclic citrullinated peptide antibody titer is associated with increased risk for interstitial lung disease.

This paper is to examine the relationship between anti-cyclic citrullinated peptide (anti-CCP) antibody titers and the development of interstitial lung disease (ILD) in patients with and without rheumatoid arthritis (RA). A retrospective investigation was conducted on all adult patients tested for anti-CCP between January 1, 2007, and December 31, 2012, in a university healthcare system. Patients with specified exposures or conditions known to cause ILD were excluded. The prevalence of ILD was compared between those with and without a positive CCP. The study population was then divided into four titer groups based on anti-CCP titers: negative, low titer, moderate titer, high titer. Fisher's exact tests compared the prevalence of ILD among the anti-CCP titer groups. Multivariate logistic regression examined the association between anti-CCP and ILD while controlling for confounders. These analyses were repeated in two subgroups: a "confirmed RA" subgroup and an "unconfirmed RA" subgroup. Two thousand and thirty patients met inclusion criteria and 453 of those had confirmed RA. Progressively higher anti-CCP titer groups developed an increasingly higher prevalence of ILD (p < 0.01). When adjusting for age, tobacco, and a diagnosis of RA, higher anti-CCP titer groups continued to correlate with an increased prevalence of ILD (OR 1.47, 95% CI 1.10-1.96, p < 0.001). This study is the first to show that progressively higher anti-CCP titers correlate with increasing prevalence of ILD, even when adjusting for confounders.

Multicenter, observational clinical study of abatacept in Japanese patients with rheumatoid arthritis

The aim of this study was to assess abatacept in rheumatoid arthritis (RA) patient. Patients (20 men, 89 women, aged 61.9 ± 10.4 y) who responded inadequately to conventional synthetic disease-modifying anti-rheumatic drug were treated with abatacept for 24-months. Disease activity score in 28 joints (DAS28-CRP) was evaluated. Of 109 patients, 82 (75.2%) were on methotrexate (MTX; mean dosage 9.0 ± 2.7 mg/week); 48 (44.0%) were naive to biologics and 61 (56.0%) had failed biologics. The 1- and 2-year retention rates were 77% and 53%, respectively. At 24-months, the DAS28-CRP remission rates were 62.8% in the biologic-naïve patients, and 33.3% in the biologic-failure patients (p < .01), while the structural remission rates were 83.9% and 73.1%, respectively (p = .461). Abatacept was equally effective in RA patients who were and were not on concomitant MTX. Biologic-naïve was associated with better clinical outcome. Abatacept was effective in patients who showed decreasing anti-CCP antibody titers or serum MMP-3 levels during treatment. Infection was the most frequent adverse effect of abatacept therapy. In conclusion, abatacept is more effective in biologic-naïve than in biologic-failure RA patients with or without concomitant use of MTX. Abatacept is more effective in RA patients with than without decreasing serum MMP-3 or anti-CCP antibody titers during treatment.

A Study of Correlation of Disease Severity with Antibody Titers in Rheumatoid Arthritis

Introduction: Rheumatoid Arthritis (RA) is one of the most frequent autoimmune diseases in the world which affects about 1% of people. Anti-Cyclic Citrullinated Peptides (Anti-CCP) is shown to be more specific than rheumatoid factor in the diagnosis of RA. This test becomes positive in early stage of disease and it has a high predictive value. Aim: To correlate the relationship between anti-CCP antibody and rheumatoid factor titers and disease activity scores. Materials and Methods: A cross-sectional study was performed in 50 patients with RA for evaluating the relation between anti-CCP antibody titer and Disease Activity Score 28 (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). A detailed examination of each patient including their demographic characteristics, duration of disease, number of tender and swollen joints, ESR and C-reactive protein, patient’s and physician’s global assessment by VAS (0-10) and titers of rheumatoid factor and nti-CCP antibody. Patients who fulfilled the ACR-EULAR 2010 criteria were included. The statistical analysis was done using Pearson’s correlation coefficient. A p-value of less than 0.05 was considered significant. Results: Of the 50 patients which were included (mean age, 44.82 range, 18-70), 38 were females and 12 were males. Mean ESR was 54±27 mm/hr and Mean CRP was 17.277±23.41 mg/dL. Mean DAS 28 was 5.955±0.962; mean SDAI was 46.9±27.1 and CDAI 28.9±10.8. There was positive correlation (p<0.001) between DAS28 and SDAI (r=0.550) and CDAI (r=0.808). Anti-CCP level was associated with SDAI (r=0.317) and CDAI (r=0.282) (p<0.05). Conclusion: There was significant correlation in the titers of anti-CCP and disease activity indices-SDAI and CDAI. Patients with higher levels of anti-CCP antibody had greater activity.

Selective inhibition of Tfh cells by a small molecule inhibitor abrogates progression of experimental inflammatory arthritis

Abstract Background Rheumatoidarthritis (RA) is an inflammatory autoimmune disease characterized by T cell infiltration in the joints and autoantibody production. T follicular helper (Tfh) cells are a unique subset of CD4+ T cells regulating antibody production in B cell follicle. Our previous studies have showed that increased circulating Tfh cells were correlated with anti-CCP antibody titer and disease activity in active RA patients, indicating that Tfh cells may play an important role in RA pathogenesis. Here we investigate the therapeutic potential of a small molecule inhibitor targeting Tfh cells (SMI-Tfh) in mice with collagen-induced arthritis (CIA). Methods CIA was induced in DBA/1 mice by immunization with chicken type II collagen. Following the onset of clinical arthritis, mice were treated with SMI-Tfh (50mg/kg/day) for 10 days. Arthritis progression was monitored daily and recorded by the paw swollenness. Blood, spleen, and affected paws were collected at the end of the study. Tfh cells were examined and defined by CD4+CXCR5+ICOS+via flow cytometry and further confirmed by immunohistochemistry staining in spleen. Results Mice developed arthritis four weeks after immunization with type II collagen. Treatment with SMI-Tfh significantly reduced the disease progression/activity in mice with CIA. SMI-Tfh significantly inhibited the frequency of Tfh cells in spleen (P&amp;lt;0.01), but not the frequency of circulating Tfh cells in CIA mice (P&amp;gt;0.05). Conclusion The small molecule inhibitor SMI-Tfh selectively inhibits Tfh cells and abrogates progression/activity of inflammatory arthritis in CIA mouse model. Treatment with SMI-Tfh in CIA mice provides a potential strategy for joint protection and may be beneficial in RA patients.

Periodontal pathogens and the association between periodontitis and rheumatoid arthritis in Korean adults.

PurposePeriodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults.MethodsA total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices.ResultsThe RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020).ConclusionsThe GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.

High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study

BackgroundAlthough both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA.MethodsMethotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: “low/low-C” (RF < 55 IU/ml, anti-CCP < 42 U/ml), “high/high-C” (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and “middle-C” (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes.ResultsBaseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2–14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment.ConclusionsRF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA. Baseline RF/anti-CCP titers may serve as indices that aid infliximab treatment.Trial registrationClinicalTrials.gov, NCT00691028. Retrospectively registered on 3 June 2008.

High titer of anti-citrullinated peptide antibody is a risk factor for severe carotid atherosclerotic plaque in patients with rheumatoid arthritis: the TOMORROW study.

Cardiovascular disease is one of the complications of rheumatoid arthritis (RA). We researched the morbidity and severity of existing carotid atherosclerosis plaque and associated risk factors in patients with RA. This study included 413 participants, including 208 patients with RA and 205 age- and sex-matched healthy volunteers. Carotid ultrasound, clinical data collection and assessment of cardiovascular risk factors were performed. Atherosclerotic plaque was defined as an intima-media thickness ≥ 1.1 mm. Severity of plaque was assessed by plaque score, defined as the sum of the maximal thickness of all plaques in bilateral carotid arteries. Data were analyzed from 200 patients with RA and 202 controls. Carotid plaque was observed more frequently in patients with RA than controls (47.0 vs. 36.1%, P = 0.027). Moreover, plaque score was significantly higher in RA patients (P = 0.032). In logistic regression analysis, RA represented an independent risk factor for the presence of plaque (adjusted odds ratio, 1.68; 95% confidence interval, 1.03-2.74). Comparing RA patients with and without plaque, anti-cyclic citrullinated peptide (anti-CCP) antibodies titer was significantly higher in patients with plaque (315.8 ± 454.1 U/mL) than in patients without (165.7 ± 281.1 U/mL; P = 0.005). Moreover, multiple linear regression analysis clarified that anti-CCP antibody titer was associated with plaque score in patients with RA. High prevalence of any carotid plaques and severe carotid plaques were more frequent in patients with RA. High titer of anti-CCP antibodies represented a risk factor for severe carotid atherosclerotic plaque in patients with RA.

Erosive arthritis and anti-cyclic citrullinated peptide antibodies in systemic sclerosis

Background: The frequency and characteristics of erosive arthritis in systemic sclerosis (SSc) remains unclear. The aim of the study was to determine the prevalence and characteristics of erosive arthritis and to define the role of anti-CCP antibodies in the differential diagnosis of joint involvement in SSc. Methods: One hundred and fifty patients who met the 1980 American College of Rheumatology (ACR) criteria and/or Leroy and Medsger criteria for SSc were assessed. Results: Among the 150 SSc patients, 139 were women. Their median age was 45.12 ± 13.59 years and disease duration ( first non-Raynaud symptom) of 9.7 years. Of these patients, 5 patients were classified as having limited SSc, 103 as limited cutaneous SSc and 42 as diffuse cutaneous SSc. Joint involvement was characterized as arthralgia in 95 (63%) patients, arthritis in 60 (40%) patients, erosive arthritis in 21 (14%) and systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome in 7 patients. The prevalence of diffuse cutaneous involvement (50%) (P = 0.01), digital ulcers (81%) (P = 0.009), interstitial lung disease (81%) (P = 0.009) and anti-topoisomerase I antibodies (P = 0.01) was higher in patients with erosive arthritis. Anti-CCP antibodies were found in 14 of the 150 (9.4%) cases. A statistically significant association between the presence of anti-CCP antibodies and the presence of arthritis (P = 0.01), erosive arthritis (P = 0.01) and SSc-RA overlap syndrome (P < 0.05) was noted. High titers of anti-CCP antibodies were found in patients with SSc-RA overlap syndrome. Conclusion: Erosive arthritis is not rare in SSc, and it might be a marker of severe disease. Anti-CCP antibodies can be present in patients with SSc, and high titers of anti-CCP antibodies may be indicative of SSc-RA overlap syndrome.