Rheumatoid Factor Titer Research Articles

Association of cytokine patterns and clinical/laboratory parameters, medication and periodontal burden in patients with rheumatoid arthritis (RA)

To evaluate serum levels of the following cytokines in rheumatoid arthritis subjects with periodontal disease: Interleukin-6, -10, -17, and -23. Patients with rheumatoid arthritis frequently suffer from periodontal disease. Both diseases partly result from a dysregulated immune response. The current study aimed to quantify Interleukin-6, -10, -17, and -23 levels in rheumatoid arthritis. It should be investigated if the periodontal disease would have additional modifying effects. A total of 157 patients were included. Serum levels of IL-6, -10, -17, and -23 were measured by ELISA. Serum IL-10 increased with longer duration of morning stiffness and with higher rheumatoid factor and anti-cyclic citrullinated peptide titres. IL-10 was also elevated with longer duration of prednisolone (< 5 mg daily) and leflunomide therapy. Subjects with lower erythrocyte sedimentation rate/longer leflunomide therapy displayed more missing teeth/more clinical attachment loss. IL-17 was higher in subjects with fewer missing teeth if the following criteria were fulfilled: shorter prednisolone (< 5 mg) and methotrexate therapy, more swollen joints, longer morning stiffness. IL-23 finally was increased in subjects with higher rheumatoid factor and in those with higher periodontal probing depth/clinical attachment loss in the following situations: lower rheumatoid factor and shorter leflunomide therapy. Subjects suffering from dental/periodontal burden show an aberrant systemic cytokine availability of serum IL-6, IL-10, IL-17 and IL-23 related to disease activity and medication. This examination underlines the complexity of potential interactions between disease activity and medication related to periodontal burden.

Phenotypic variability in a child with Felty\u2019s syndrome: a case report

BackgroundFelty’s syndrome (FS) is characterized by the triad of rheumatoid arthritis (RA), splenomegaly and neutropenia. The arthritis is typically severe and virtually always associated with high-titer rheumatoid factor. The presence of persistent neutropenia is generally required to make the diagnosis. Most patients diagnosed with FS are aged 50–70 years and have had RA for more than 10 years. It is rarely seen in patients with juvenile idiopathic arthritis (JIA), with only five cases having been reported throughout the world.Case presentationThe present study describes the case of a 14-year-old female with a seven-year history of polyarticular JIA, presenting with splenomegaly, hepatomegaly, cholestasis and thrombocytopenia. However, she occasionally developed neutropenia. Titers of rheumatoid factor and anti-CCP were persistently high, and the antinuclear antibody titer was 1:320, while the antibody results for anti-dsDNA and anti-Sm were negative. Serum levels of IgA, IgG, IgM and IgE were all persistently elevated, and the ratio of CD19+ lymphocytes in the subgroups of lymphocytes was persistently high. The level of complements was normal. No STAT3 and STAT5B mutations were found by next-generation sequencing. The patient did not respond to methotrexate, prednisolone, hydroxychloroquine (HCQ), sulfasalazine and etanercept but was responsive to rituximab.ConclusionsJIA, thrombocytopenia and splenomegaly are the most common and important features in six children with FS, while persistent neutropenia is not seen in all these patients. No complement deficiency has been found in children with FS so far. Manifestations of FS without neutropenia may be extremely rare. There are differences between adults and children in the clinical and laboratory features of FS.

Serum, synovial and mRNA expression of interleukin-33 in juvenile idiopathic arthritis patients: Potential role as a marker of disease activity and relation to musculoskeletal ultrasound

Aim of the workTo measure interleukin-33 (IL-33) serum and synovial fluid (SF) levels as well as its relative expression in peripheral blood mononuclear cells (PBMC) of juvenile idiopathic arthritis (JIA) patients and to study their relation to clinical, laboratory and musculoskeletal ultrasound characteristics, disease activity and functional status. Patients and methodsThe study included 60 JIA patients and 60 healthy controls and SF levels were measured in 20. Juvenile arthritis disease activity score (JADAS27) and Juvenile Arthritis Multidimensional Assessment Report (JAMAR) were assessed; Ten-joint grey scale (GS) and power Doppler (PD) MSUS score was performed. Rheumatoid factor (RF) titer and C-reactive protein (CRP) levels were measured. ResultsIn JIA patients, serum IL-33 levels (median 12.6; 7.4–23.8 ng/l) and its relative mRNA expression (median 3.3; 2.5–3.7) were significantly higher than their levels in the controls (median 1.7; 0.8–2.4 ng/l and median 1 ng/ml; p < 0.001). Polyarticular subtype (n = 20) had higher IL-33 serum levels compared to oligoarticular (n = 28, p < 0.001) and systemic-onset (n = 12, p = 0.006) subtypes. In JIA patients, the serum and SF levels of IL-33 significantly correlated with JADAS27 (p < 0.001 and 0.002 respectively), CRP (p < 0.001 and 0.007 respectively), GS (p < 0.001 and 0.001 respectively) and PD (p < 0.001 and 0.005 respectively). Serum IL-33 correlated with RF (p = 0.039) while, SF IL-33 correlated with physical function (p = 0.02). ConclusionsJIA patients have significantly elevated IL-33 serum concentrations and mRNA expression that considerably correlated with different inflammatory parameters, RF and physical function suggesting that it could be a valuable marker of JIA disease activity and implies a possible prognostic role.

Serum C-Reactive Protein/Albumin Ratio in Rheumatoid Arthritis and its Relationship With Disease Activity, Physical Function, and Quality of Life

This study aims to evaluate the relationship between C-reactive protein (CRP)/albumin ratio (CAR) and disease activity, quality of life (QoL), and physical function in rheumatoid arthritis (RA). A total of 121 RA patients (22 males, 99 females; mean age 57.6±11.2 years; range, 32 to 85 years) applying to Ankara University School of Medicine Rheumatology Outpatient Clinic between January 2019 and February 2019 were included in this cross-sectional study. The inclusion criteria were fulfilling the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria, being over 18 years and accepting to participate in the study. Demographic and clinical parameters including serum erythrocyte sedimentation rate (ESR), CRP and albumin levels were recorded. Disease activity was measured using Disease Activity Score 28 (DAS28)-ESR. General health, fatigue, and pain were questioned by means of a 100 mm visual analog scale (VAS). The QoL was assessed with the Rheumatoid Arthritis Quality of Life (RAQoL) Questionnaire. The functional status was determined using the Health Assessment Questionnaire (HAQ). Rheumatoid factor (RF) was positive in 56.2% of the patients. The median ESR was 19.0 mm/hour [interquartile range (IQR): 19.5] and median CRP was 5.6 (IQR: 9) mg/L. The median CAR was 1.3 (IQR: 2.1) and median DAS 28-ESR was 3.6 (IQR: 1.5). There was a significant but weak correlation between CAR and DAS28-ESR [p<0.001, Spearman's correlation coefficient (rs)=0.327]. Moreover, CAR was positively correlated with ESR, CRP, and VAS physician's global assessment (p<0.001, rs=0.497; p<0.001, rs=0.987, p<0.001, rs=0.401, respectively). However, no correlation was observed between CAR, HAQ, and RAQoL. In the RF positive group, there was a significant but weak correlation between CAR and RF titers (p=0.016, rs=0.292). We observed a positive but weak correlation between CAR and DAS28-ESR, ESR, and the RF titer. Further studies are warranted to investigate the role of CAR in RA.

Effects of Infliximab on Rheumatoid Factor &amp; Anti-cyclic Citrullinated Peptide Antibodies in Patients with Rheumatoid Arthritis

Background: Anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) are two important investigations that help in confirming the diagnosis and may help deciding strategies for the treatment. This study’s aim is to investigate the effect of infliximab, a tumor necrosis factor inhibitor on ACPA and RF in patients with rheumatoid arthritis. Patients and Method: Thirty five Iraqi patients with established RA, enrolled in this study during September 2013-May 2014. They received 3 mg/kg infliximab intravenously at weeks 0, 2, 6, and every 8 weeks thereafter in combination with methotrexate (15-20) mg. At baseline, week 24, CRP and ESR were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure ACPA, and IgM-RF (ELISA). Results: RF mean at the first visit was (106.1±25.2) IU/ml and at the second visit it reduced to (60.1±14.6) IU/ml and the difference was statistically significant, (P=0.038). ACPA mean was (466.5±61.4) U/ml at the first visit reduced significantly to reach (241.9±36.6) U/ml at the second visit (P&lt;0.001). A dramatic and significant change had been found in the disease activity; (P&lt;0.001) mean DAS 28 was (5.7±1.1) at the first visit with a range of (2.7– 8.6), at the second visit the mean was (4.5±1) and the range was (2.04–6.4). Conclusions: Anti-TNF a treatment in RA cause decrease in serum titers of RF and ACPA in patients with clinical improvement.

Prevalence and severity of periodontitis in patients with established rheumatoid arthritis and osteoarthritis.

Introduction:Periodontitis is associated with many chronic health conditions including diabetes, cardiovascular disease, and rheumatoid arthritis (RA). RA and periodontitis have similarities in inflammatory mechanism, morphology, and histopathology. Osteoarthritis (OA) is a chronic, multifactorial degenerative disease characterized by the deterioration of cartilage in joints.Objective:The aim of this study was to evaluate the prevalence and severity of periodontal disease in patients with established RA and OA.Materials and Methods:A total of 200 patients reporting to the Department of Orthopaedics, KIMSDU, Karad were included in the study. Patients were divided into two groups: Group 1 that included 100 patients with established RA diagnosed according to American College of Rheumatology (ACR) classification 1987 criteria and Group 2 that comprised 100 patients diagnosed with OA. Demographic profile, medical and dental history, oral hygiene practices, and smoking status of study participants were recorded. Periodontal status of the patients were evaluated using the simplified oral hygiene index (OHI-S), Loe and Silness gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL). On the basis of the CAL score periodontitis severity was defined as slight, moderate, and severe. Rheumatoid Factor (RF) and C-reactive protein (CRP) were considered as a serological marker in RA. Serological tests were performed to measure RF and CRP. Periodontal parameters and serological tests were correlated.Results:This study reported 45% severe periodontitis prevalence in RA compared to OA group, which was 33%. Severity of periodontitis is significantly greater in RF positive RA group with mean CAL 5.38 mm compared to RF negative RA group with mean CAL 2.81 mm (P = 0.001). There was moderate positive correlation found between RF titer and severity of periodontitis (r = 0.311).Conclusion:The severity of periodontitis was significantly higher among the patients with established RA as compared to patients with OA. RF positive patients had higher periodontal disease compared to RF negative patients. There was an increase in the mean clinical attachment loss with increase in RF titer.

Comparative analysis of rheumatoid factor levels by immune turbidimetry and latex agglutination assays among anti-cyclic citrullinated peptide-positive rheumatoid arthritis patients

Background: Rheumatoid arthritis (RA) is one of the most common contributors to the burden of chronic and debilitating polyarthritis. Materials and Methods: Over a period of 3 months, 264 symptomatic patients were tested for the presence of anti-cyclic citrullinated peptide (CCP) antibodies, and the first 50 patients with RA whose serum samples tested positive for anti-CCP (>10 AU/ml) were included in the study. Immune turbidimetric assay was employed to determine the titers of rheumatoid factor (RF) in patients of RA who have tested positive for anti-CCP and its performance was compared with latex agglutination testing modality. Results: Majority (82%) of the study population were female with a male-to-female ratio of 1:4.6. Latex agglutination test for RF using RHELAX-RF test kit yielded RF values ≥10 IU/ml in 31 (62%) patients, while the Immunoturbidimetric test: SPECTRUM RF Test Kit imparted RF titers ranging between 2.4 and 53.76 IU/ml, with a median RF titer of 22.22 IU/ml. The percentage agreement between the latex agglutination and immune turbidimetry assay for analyzing RF was 88%, with a strong positive correlation between latex agglutination and immune turbidimetry assay for RF (Spearman coefficient: r = 0.8097). Conclusion: Since the updated American College of Rheumatology/European League Against Rheumatism classification of RA underscores the precise titers of RF and anti-CCP in scoring RA, absolute titers of RF conferred by the immunoturbidimetry could be a welcome relief to slash inter-observer variations and hand out titers to better classify and treat patients of RA.

Anti-carbamylated protein antibody isotype pattern differs between palindromic rheumatism and rheumatoid arthritis.

Background:A restricted response against citrullinated peptides/proteins, with less isotype usage, has been found in palindromic rheumatism (PR) in comparison with rheumatoid arthritis (RA). We hypothesized that this different antibody response may be observed for other post-translational modified proteins. We compared the prevalence and isotype usage of two specificities of anti-carbamylated peptide/protein antibodies (Anti-CarP) in patients with PR and RA.Methods:Cross-sectional study including 54 patients with pure PR and 53 patients with RA, matched by sex, age, disease duration and ACPA. Anti-CarP specificities were determined by home-made enzyme-linked immunosorbent assay tests using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) and fetal calf serum (FCS) homocitrullinated protein as antigens. IgG, IgA and IgM isotypes were measured.Results:Anti-CarP were positive (CFFHP or FCS) in 24% and 64% of patients with PR and RA, respectively (p < 0.005). All Anti-CarP isotype proportions were significantly lower in PR than in RA: Anti-CarP-IgG (24% versus 51%), Anti-CarP-IgA (7% versus 34%) and Anti-CarP-IgM (7% versus 36%). Mean titers of Anti-CarP isotypes were also lower in PR. In Anti-CarP positive patients, the isotype distribution differed between PR and RA: IgG Anti-CarP was used in all PR patients and in 79% of RA patients. By contrast, a significantly lower isotype usage of both IgA (31% versus 53%) and IgM (31% versus 56%) was observed in PR patients. No significant differences in clinical or demographic characteristics were observed according to Anti-CarP status in PR patients, except for a higher prevalence of ACPA and higher mean titers of ACPA and rheumatoid factor in Anti-CarP positive patients.Conclusion:Anti-CarP are found in patients with PR but in a lower proportion and with a different isotype usage from in RA, suggesting a distinct B cell response to homocitrullinated antigens in PR.

Serum and synovial matrix metalloproteinases 1 and 3 in patients with early rheumatoid arthritis: potentially prospective biomarkers of ultrasonographic joint damage and disease activity

BackgroundMatrix metalloproteinase-1 (MMP-1) and MMP-3 play important roles in the pathogenesis of rheumatoid arthritis (RA) and have been suggested as markers of disease activity and joint damage.Objective The aim was to analyze the clinical significance of MMP-1 and MMP-3 in relation to markers of disease activity and degree of joint destruction in patients with early RA at presentation and after 6 months.Patients and methodsBaseline levels of serum MMP-1 and MMP-3 were assessed in 50 patients with early RA (symptoms <1 year), 20 patients with osteoarthritis (OA), and 20 age-matched and sex-matched healthy controls. Serum MPP-1 and MPP-3 were correlated with disease activity markers [erythrocyte sedimentation rate (ESR), C-reactive protein, disease activity score 28–ESR] and radiographic joint damage using simple erosion narrowing score and musculoskeletal ultrasound of wrist and hand joints. Baseline synovial fluid MMP-1 and MMP-3 levels were evaluated for 20 patients indicated for arthrocentesis.ResultsBaseline serum MMP-1 and MMP-3 were significantly higher in RA group versus OA group and healthy controls (P<0.001). Synovial MMP-1 and MMP-3 levels were significantly higher in RA versus OA group. Serum MMP-1 and MMP-3 levels significantly correlated with rheumatoid factor titers, anticyclic citrullinated peptide, disease activity score 28-ESR score, joint erosions, and Outcome Measures in Rheumatology score of synovitis and Doppler signals. Serum MMP-1 did not correlate with C-reactive protein, but significantly correlated with the number of erosions at presentation and on follow-up. The number of patients with erosions and the number of erosions per patient increased after 6 months and correlated with serum MMP-1 and MMP-3. The best cutoff values of serum MMP-1 and MMP-3 to discriminate between RA and healthy controls were greater than 20 and greater than 50ng/ml, respectively.ConclusionElevated serum levels of MMP-1 and MMP-3 can be used as an indicator of disease activity in patients with early RA and can reflect the degree of joint damage and correlate with the number of new joint erosions.

Factors Associated with Extra Articular Manifestations in Rheumatoid Arthritis

Introduction: Rheumatoid arthritis is a chronic, systemic and inflammatory joint disease that primarily affects the joints and can be associated with a variety of extra-articular manifestations. The aim of this study is to determine the frequency and the factors associated with those extra-articular manifestations.Materials and methods: Cross-sectional study of hospitalized cases of rheumatoid arthritis in our department between January 2012 and January 2018. We studied the prevalence of the extra-articular manifestations and associated factors. The analysis was done by the software EPI INFO 3.5.4.Results : 294 cases of rheumatoid arthritis included. The average age was 53.2 years +/- 12.3 with female predominance F / M = 6.1. The diagnosis lag time was 10.7 +/- 6.9 years. Half of our patients (50.7%) had systemic manifestations. In order of frequency, we distinguish: Osteoporosis (39.6%), Sjögren's syndrome (22.1%), pulmonary involvement (16.1%), dermatological manifestations (8.8%), cardiac involvement (8.8%), ocular involvement (3.1%) carpal tunnel syndrom (1.3%) and vasculitis (1.3%). The extra-articular manifestations were associated with several factors on bivariate analysis : advanced age (p = 0.014), longer duration of disease (p = 0.006), deformities (p = 0.000), seropositivity (p = 0.02), high titers of rheumatoid factor (p = 0.03), destruction (p = 0.02), bone erosions (p = 0.012) and non-use of biotherapy (p = 0.04). Factors whose association was statistically significant, after multivariate logistic regression analysis, were: advanced age (p = 0.04, OR = 1.02 [1.001-1.043], and longer duration of disease (p = 0.02 OR = 1.04 [1.005-1.082]).Conclusion: In our Moroccan context, half of the patients with rheumatoid arthritis had extra-articular manifestations. Older patients with longer disease evolution are the most involved.

Exposure to ambient air pollution and autoantibody status in rheumatoid arthritis.

To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status METHODS: We performed a cross sectional study utilizing enrollment data from participants in the Veterans Affairs rheumatoid arthritis registry. HLA-DRB1 shared epitope (SE), smoking, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (ACPA) status were collected. Mean exposure levels were obtained for AP (NO2, SO2, particulate matter [PM2.5, PM10], and ozone) from air quality monitoring stations at patients' residential zip codes in the year prior to enrollment. Multivariable logistic and ordinary least squares regression models were used to determine independent associations of AP with RA seropositivity and autoantibody concentration. The cohort included 557 veterans (90% male, 76% Caucasian), with mean age of 70 years and mean disease duration of 13 years. The majority were HLA-DRB1 SE, RF, and ACPA positive (73%, 79%, and 76%, respectively). In univariate models, PM2.5 exposure was associated with higher ACPA concentration (p = 0.009). Similarly, in multivariable regression models, PM2.5 exposure was independently associated with higher ACPA concentration (p = 0.037). Current smoking independently predicted RF and ACPA positivity and titers, while HLA-DRB1 SE alleles were associated with RF positivity and ACPA positivity and titers. In an elderly cohort of RA patients, fine particulate matter (PM2.5) exposure independently predicted higher ACPA concentration. Further study of fine particulate matter in the pathogenesis of RA is warranted. Key Points • A study that integrates both genetic and environmental exposure data, relative to RA autoantibody status. • Of different air pollutants measures, exposure to fine particulate matter (PM2.5) appears to be most closely linked to ACPA titers.

Rheumatoid Arthritis-Associated Interstitial Lung Disease: Clinical Characteristics and Predictors of Mortality

Introduction: Interstitial lung disease (ILD) is a serious extraarticular manifestation of rheumatoid arthritis (RA), but no evidence-based therapy exists. Ongoing studies investigate the role of antifibrotic therapies for progressive fibrosing ILD (PF-ILD), including RA-ILD. The aim of the present study was to investigate the frequency of PF-ILD and the clinical characteristics of RA-ILD in a well-characterised, population-based cohort. Methods: We identified patients with RA-ILD diagnosed and followed at the ILD referral centre in Aarhus, Denmark, from 2004 to 2016. Adjusted hazard rate ratios for death were estimated using Cox regression models. The presence of PF-ILD was assessed using recently proposed definitions of relative forced vital capacity (FVC) decline ≥10%, relative diffusion capacity of the lung for carbon monoxide (DLco) decline ≥15% or worsening symptoms or a worsening radiological appearance accompanied by a ≥5 to <10% FVC decline. Results: We identified 102 patients with RA-ILD, and 52% had PF-ILD. Mean follow-up was 3.8 years and median survival was 7.1 years. Thirty-eight patients died during follow-up, and most deaths were from respiratory causes. Predictors of mortality in a multivariate model were DLco and high titres of IgM rheumatoid factor. Conclusion: PF RA-ILD was common and the associated mortality was high.

Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry.

We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with abnormalities on pulmonary function tests (PFTs). We studied RA serostatus and PFT abnormalities within a RA registry. RA serostatus was assessed by research assays for cyclic citrullinated peptide (CCP) and rheumatoid factor (RF). Outcomes were abnormalities on clinically indicated PFTs, including restriction, obstruction, and diffusion abnormality. Logistic regression was used to obtain ORs and 95% CIs for the PFT abnormalities by RA serologic phenotypes independent of lifestyle and RA characteristics. Among 1272 analyzed subjects, mean age was 56.3years (SD 14.1), 82.2% were female, and 69.5% were seropositive. There were 100 subjects with abnormal PFTs. Compared with seronegativity, seropositivity was associated with increased odds of any PFT abnormality (multivariable OR 2.29, 95% CI 1.30-4.03). When analyzing type of PFT abnormality, seropositivity was also associated with restriction, obstruction, and diffusion abnormalities; multivariable ORs were 2.48 (95% CI 1.26-4.87), 3.12 (95% CI 1.28-7.61), and 2.30 (95% CI 1.09-4.83), respectively. When analyzing by CCP and RF status, the associations were stronger for RF+ than for CCP+ (any PFT abnormality OR 1.99, 95% CI 1.21-3.27 for RF+ vs. RF-; OR 1.67, 95% CI 1.03-2.69 for CCP+ vs. CCP-) with a dose effect of higher RF titer increasing odds for each PFT abnormality (p for trend < 0.05). Seropositive RA patients had two-fold increased risk for abnormalities on PFTs performed for clinical indications compared with seronegative RA. Patients with seropositive RA, particularly those with high-titer RF positivity, may be more likely to have obstructive and restrictive abnormalities, independent of smoking.Key points• Due to the known excess pulmonary morbidity/mortality in RA, we studied the relationship of rheumatoid arthritis (RA)-related autoantibodies with pulmonary function test (PFT) abnormalities using a large RA registry.• We evaluated whether presence and levels of cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were associated with restriction, obstruction, and diffusion abnormalities on PFTs among 1272 subjects with RA.• Seropositivity was associated with two-fold increased risk for any PFT abnormality, independent of confounders including smoking. Higher titers of RF conferred greatest risk for all PFT outcomes: obstruction, restriction, and diffusion abnormality.• These results provide evidence that patients with RA should be closely monitored for pulmonary involvement, particularly those with high-titer RF seropositivity.

Anti-citrullinated protein antibody titre as a predictor of abatacept treatment persistence in patients with rheumatoid arthritis: a prospective cohort study in Japan

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment.Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation.Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months.Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 Predicts the Changes of Rheumatoid Factor Titers in Rheumatoid Arthritis.

The aim of this longitudinal study was to examine the clinical significance of soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) in patients with rheumatoid arthritis. We gathered demographic and clinical data for a large rheumatoid arthritis cohort at 3 time points. Blood samples were collected at each time point; the number of samples was 282 cases in 2012, 431 cases in 2013, and 500 cases in 2014. Plasma sLOX-1 was measured by enzyme-linked immunosorbent assay. Correlations between sLOX-1 and clinical data were analyzed. Predictive factors associated with changes in sLOX-1 and rheumatoid factor (RF) were analyzed by multivariate linear regression. Plasma sLOX-1 level was significantly correlated with RF titer and other clinical parameters. The longitudinal analyses showed that changes in sLOX-1 were significantly correlated with changes in RF titers and with those at baseline. Multivariate linear regression analysis revealed that changes in RF and baseline RF were predictive factors for changes in sLOX-1. Conversely, the changes in RF were significantly correlated with the changes in sLOX-1 in all years. A stepwise regression analysis showed that the change in sLOX-1 was a predictive factor for the change in RF. The change in sLOX-1 has predictive value for assessing the change in RF, indicating the usefulness of sLOX-1 in clinical practice.

Assessment of Musculoskeletal Ultrasound Guided Injection of The New Regenerative Medicine Techniques (Neural Prolotherapy and Platelet Rich Plasma) Impact versus Well Established Techniques (Steroid Injection) in Cases of Carpal Tunnel Syndrome Secondary to Rheumatoid Arthritis

Background: Rheumatoid arthritis is a systemic rheumatic disease characterized by symmetrical, often erosive and deforming poly-arthritis with extra-articular manifestations in 10–20% of patients, especially those with high titers of rheumatoid factor. Extra articular pathology includes bursitis, tendonitis and neuritis, which results from entrapment, nerve ischemia due to vasculitis or drugs used to treat this condition.Carpal tunnel syndrome is the most common compression neuropathy associated with rheumatoid arthritis. Aim of the Work: To evaluate the efficacy of Neural Prolotherapy and Platelet Rich Plasma in treatment of carpal tunnel syndrome secondary to rheumatoid arthritis. Patients and Methods: Ninety patients with Rheumatoid Arthritis (RA) that were all fulfilling the 2016 ACR/EULAR classification criteria for RA. All were over the age of sixteen years at time of diagnosis, complaining of burning pain or paresthesia in the median nerve distribution of the hand. They were recruited from Rheumatology and Rehabilitation Department at Al-Hussein and Sayed Galal University Hospitals during the period from December 2018 to July 2019. Results: Neural Prolotherapy and Platelet Rich Plasma (PRP) have improved all measured parameters like visual analogue scale (VAS), nerve conduction studies and neuromuscular ultrasonography parameters in carpal tunnel syndrome secondary to rheumatoid arthritis. Conclusion: Neural Prolotherapy and Platelet Rich Plasma proved to be effective treatments of carpal tunnel syndrome secondary to rheumatoid arthritis.

Phase I trial of a novel DNA vaccine in patients (pts) with smoldering Waldenstrom macroglobulinemia (sWM).

8050 Background: Idiotypic determinants of the surface immunoglobulin (Ig) associated with a given pt’s B-cell lymphoma are unique to that tumor, and thus are a tumor-specific marker. This study aims to use an idiotype DNA vaccine to lengthen the smoldering phase of WM without inducing cross-resistance to available therapies. Administered vaccine used recombinant plasmid DNA encoding a fusion protein, consisting of autologous lymphoma scFv (pt-specific idiotype) and human CCL20 (macrophage inflammatory protein-3 alpha - MIP-3α) chemokine. Targeted delivery of this fusion protein to APCs, and subsequent processing and presentation, is hypothesized to break tolerance and generate an immune response against the idiotype, promoting eradication of antigen-expressing B-cell lymphoma cells. Methods: Pts with sWM received 3 i.d. vaccinations of pt-specific DNA vaccine at 4-week (wk) intervals (wks 0, 4 and 8). Two dose levels (500µg; 2500µg) were evaluated in a 3+3 design. Primary objective: to evaluate the vaccine’s safety and identify it’s MTD. Secondary objectives: 1) to assess immunogenicity of the vaccine 2) to determine time to symptomatic WM. Results: Between 1/2016 - 1/2019, 9 pts (7 men) were treated (500 µg: n = 3; 2500µg: n = 6). Median age at enrollment was 67 yrs (range 56-78); median time from diagnosis to 1st vaccination was 26.5 mos (8.8-120.9). MYD88 L265P + (6 pts). CXCR4 WHIM + (1 pt). With median follow up of 26.5 months (range: 8-36.4), all pts remain alive. Seven have stable disease; 2 progressed to symptomatic WM (8 mos. (1pt) and 26 mos. (1pt) from 1st vaccination). All pts completed planned therapy. No DLTs or Grade 4 AEs occurred. Ten mos. after the 3rd vaccination, 1 pt had a grade 3 pleural effusion and leukopenia with an increase in rheumatoid factor (23.1 IU/mL [normal range 0.0-15.9]) and ANA titer of 1:80; all resolved within 2 mos. Grade 1-2 AEs ( &gt; 3pts): leukopenia (6), nausea (5), anemia (4), increased creatinine (4), fatigue (4). Conclusions: Idiotype (scFv-CCL20) DNA vaccine therapy appears to be safe in pts with sWM. Results of immunogenicity assays are underway, and will inform whether tumor specific immune responses are induced. Additional follow up is required to determine time to symptomatic WM. Clinical trial information: NCT01209871.

Association of anti-cyclic citrullinated peptide antibody with clinical features in patients with psoriatic arthritis

Background: Although anti-cyclic citrullinated peptide antibody (anti-CCP Ab) is reported to be found in 5–20% of patients with psoriatic arthritis (PsA), its clinical significance has not been elucidated.Objective: To clarify the association of anti-CCP Ab with clinical features in PsA.Methods: Patients were enrolled who fulfilled the classification criteria for psoriatic arthritis (CASPAR) criteria and visited our hospital. We retrospectively compared clinical characteristics between those who were positive and negative for anti-CCP Ab and further compared changes in disease activity in the patients treated with biological disease-modifying anti-rheumatic drugs (DMARDs).Results: We examined 41 patients (11 females), seven were anti-CCP Ab-positive and 34 were negative. Age (55.0 ± 15.1 years old) and frequency of lung involvements (71.4%) in the anti-CCP Ab-positive group were significantly higher than those (40.0 ± 16.0 and 0%, respectively) in the negative group (p < .05). Rheumatoid factor (RF) titer (749.4 ± 860.7 U/mL) and MMP-3 (604.8 ± 1060.6) in the anti-CCP Ab-positive group was significantly higher than that (3.6 ± 4.4 U/mL and 111.2 ± 77.4, respectively) in the negative group (p < .05). Five patients were treated with tumor necrosis factor (TNF) inhibitors (infliximab (IFX): 3 and adalimumab (ADA): 2) in the anti-CCP Ab-positive group, while in the negative group there were 11 (IFX: 6, ADA: 4, and etanercept (ETN): 1). Within 6 months of treatment, arthritis did not improve with TNF inhibitors in the anti-CCP Ab-positive group, whereas it improved significantly in the negative group.Conclusion: In patients with PsA, anti-CCP Ab might be related to lung involvements, elderly onset, RF and MMP-3 titers, and resistance to TNF inhibitor.

Fc‐binding proteins enhance autoantibody‐induced BP180 depletion in pemphigoid

Immunoglobulins (Igs) consist of two antigen-binding regions (Fab) and one constant region (Fc). Protein A and protein G are bacterial proteins used for the purification of IgG by virtue of their high affinities for the Fc fragment. Rheumatoid factors are autoantibodies against IgG Fc fragments, which are present in the body under physiological conditions. Little is known about the influence of Fc-binding proteins on the pathogenicity of antibody-induced autoimmune diseases. Pemphigoid diseases are a group of autoimmune subepidermal blistering disorders that includes bullous pemphigoid and mucous membrane pemphigoid. IgGs targeting the non-collagenous NC16A domain of the 180-kDa bullous pemphigoid antigen (BP180) are known to induce skin fragility in mice and the depletion of BP180 in keratinocytes. In this study, mAb against NC16A in combination with Fc-binding proteins was found to enhance BP180 depletion. Although mAb against the C-terminus of BP180 does not show pathogenicity in vivo or in vitro, mAb treatment with Fc-binding proteins clearly induced skin fragility in mice and BP180 depletion in keratinocytes. Anti-BP180 mAbs and Fc-binding proteins were colocalized in the cytoplasm and at the basement membrane zone. Cell adhesion strengths were decreased in parallel with BP180 amounts. Clinically, bullous pemphigoid patients had higher rheumatoid factor titers than controls. Anti-BP180 mAb in combination with high-titer rheumatoid factor serum was found to enhance BP180 depletion. Furthermore, saliva from mucous membrane pemphigoid patients contained larger quantities of bacteria and Fc-binding proteins than controls. Our results suggest that Fc-binding proteins (rheumatoid factor or protein G) may enhance the pathogenicity of autoantibodies in pemphigoid diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Correlation of level of expression of Wnt Signaling Pathway Inhibitor Dickkopf-1 with disease activity in Elderly patients of Rheumatoid Arthritis: A cross sectional study

Objective: To correlate the level of Dickkopf-1 (DKK-1) and its role in rheumatoid arthritis (RA) patients of elderly age group.&#x0D; Methods: Serum samples were collected elderly RA patients fulfilling the inclusion criteria coming to Geriatric outdoor clinic between June 2018 to September 2018. DKK-1 was detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.&#x0D; Results: Twenty one patients were enrolled in study period. The serum level of DKK-1 was significantly higher in patients with severe RA with high DAS score (p &lt; 0.01); The serum DKK-1 level was correlated with T-score (r= -0.588; p = 0.005), Z-Score(r= -0.458, p = 0.037) and the larson score of radiologic change (r = +0.673, p = 0.001) in RA, however not correlated significantly with ESR, CRP.&#x0D; Conclusion: DKK-1 may serve as a biomarker of bone erosion and correlates with the disease activity in RA patients of elderly age group.&#x0D; Keyword: DKK 1, Rheumatoid arthritis, Geriatric, Osteoporosis.