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Background: Rheumatoid arthritis (RA) and periodontal disease (PD) are both characterized by an inflammatory reaction. Anti-cyclic citrullinated peptide (anti-CCP) is a common diagnostic test for RA. Anti-CCP is proposed to be used as a serological biomarker to detect PD in patients with RA. Methods: A case-control study was designed for 94 subjects; 42 patients with RA and 52 without RA. PD and its types were investigated among these subjects. An enzyme-linked immunosorbent assay (ELISA) test was used to measure anti-CCP levels in these subjects. Results: Subjects were recategorized into four groups after PD diagnosis: group 1 for RA with PD (34.04%); group 2 for RA only (10.63%); group 3 for PD only (30.85%); and group 4 for individuals without RA and PD (24.46%). Anti-CCP may be considered an effective biomarker for predicting the development of PD in RA patients based on five current results found in group 1 compared to other groups. These included the detection of significantly higher anti-CCP levels, a high sensitivity (63.15%), low specificity (50%), higher cut-off value (58.53 U/ml), high positive predictive value (94.73%), and low negative predictive value (8.69%) of anti-CCP. Chronic periodontitis is the most common and has a significant association with elevated levels of anti-CCP. Conclusion: Measuring the anti-CCP level in RA patients may be a good indicator for PD diagnosis based on the suggested cut-off value. The sensitivity of the test is sufficiently reliable to produce true positive results. Anti-CCP may also be useful in the diagnosis of PD type, especially chronic periodontitis. [ABSTRACT FROM AUTHOR]

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real‐time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1β and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1β. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with rheumatoid arthritis (RA) are prone to develop infections. Methods: Accordingly, 195 untreated early (e)RA patients and 398 healthy controls were selected from women in Tatarstan's cohort to study infectious history in the anamnesis (four criteria) and in the previous year (16 criteria). Information about annual infections was collected face-to-face from year to year by a qualified rheumatologist/general practitioner and included the active use of information from medical records. Results: In the anamnesis, tuberculosis, and pneumonia, and in the previous year, respiratory tract infections, skin infections, and herpes simplex virus reactivation incidence were reported to be increased in eRA patients, as well as the event number and duration of acute and chronic tonsillitis. Moreover, more bacterial-suspected upper respiratory infections and urinary tract infections were retrieved in sporadic eRA patients as compared to familial eRA patients. An elevated immunization against CCP prevented respiratory tract infection in those with HSV exacerbation. Finally, associations were retrieved between infection (event number/delay) and RA indices: (i) chronic tonsillitis exacerbations with disease activity and health assessment (HAQ) in familial eRA; (ii) bacterial-suspected upper respiratory infections with the number of swollen and tender joints in sporadic eRA; and (iii) HSV exacerbation with inflammation in eRA patients with negative/low response against CCP. Here, we demonstrate the complex nature of the interplay of RA with specific infections. Conclusions: For the first time, differences in the patterns of annual trivial infections and their links with RA indices were found in cohorts of familial and sporadic cases of the disease. Additionally, for the first time, we identified a remarkable relationship between early RA and exacerbations of chronic tonsillitis, as well as tuberculosis in the patient's history. Altogether, this study supports the existence of a complex interplay between infections and RA at onset driven by familial status and the presence of anti-CCP Ab at elevated levels. [ABSTRACT FROM AUTHOR]

Objectives: The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID‐19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID‐19. Methods: The serum samples obtained from 176 hospitalized COVID‐19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID‐19. Also, the serum samples collected from healthy subjects before the COVID‐19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble‐stranded DNA (anti‐dsDNA), cytoplasmic‐anti neutrophil cytoplasmic antibody (c‐ANCA), perinuclear ANCA (p‐ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti‐CCP) occurrence was evaluated using a solid‐phase enzyme‐linked immunosorbent assay (ELISA). Results: The results showed that the occurrence of ANAs, anti‐dsDNA, anti‐CCP, c‐ANCA, and p‐ANCA was significantly higher in the COVID‐19 patients compared to serum obtained from healthy subjects (p <.0001, p <.0001, p <.0001, p <.05, and p <.001, respectively). The positive number of anti‐CCP tests increased significantly in severe COVID‐19 compared to the moderate group (p <.01). Conclusion: Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti‐CCP in a severe form of COVID‐19. [ABSTRACT FROM AUTHOR]

Objectives: The significance of T helper 17 (Th17) cells in the pathogenesis of rheumatoid arthritis (RA) has recently been demonstrated in many studies. Retinoic acid receptor‐related orphan receptor γt (RORγt) is a transcription factor that is specifically involved in the generation of Th17 cells. Besides, the chemokine receptor CCR6, the receptor for CCL20, is characteristically expressed by these cells. Considering the pivotal roles of Th17 cells in RA pathogenesis, in this study, we assessed the gene expression of CCR6 and RORγt in the peripheral blood leukocytes of new case RA patients. Also, we evaluated their association with anticyclic citrullinated peptide (anti‐CCP) antibodies and disease activity. Methods: Forty‐five new case RA patients and 45 healthy persons have been recruited in this investigation. The gene expression of CCR6 and RORγt was evaluated by quantitative real‐time PCR (qRT‐PCR), and anti‐CCP antibodies plasma levels were measured using the enzyme‐linked immunosorbent assay (ELISA) technique. Disease activity was measured according to the disease activity score‐28 (DAS‐28) formula. Results: The gene expression of CCR6 and RORγt increased remarkably in new case RA patients compared to healthy controls (p <.05 and p <.01, respectively). Moreover, there was a positive correlation between RORγt gene expression and parameters, including gene expression of CCR6 (p =.001, r =.461), plasma levels of CCL20 (p =.0009, r =.477), ESR (p =.004, r =.419), DAS‐28 (p =.006, r =.402), anti‐CCP (p =.019, r =.346), and RF (p =.001, r =.451). Also, CCR6 gene expression was positively associated with the DAS‐28 (p =.037, r =.310), plasma levels of anti‐CCP (p =.037, r =.312), and ESR (p =.029, r =.327). Conclusion: Increased gene expression of CCR6 and RORγt in peripheral blood leukocytes of new case RA patients may contribute to the exacerbation and pathogenesis of RA. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is an autoimmune disorder associated with a chronic inflammation, which can cause joint damage and extra-articular complications. Anti-citrullinated protein antibody (ACPA) positivity is accompanied by poor prognosis in RA, and testing for ACPA has become traditional practice in the context of RA diagnosis. Objective: The aim of the study was to estimate the prevalence of low bone mineral density (BMD) among female patients with RA using dual energy x-ray absorptiometry (DEXA), and to study the correlation between BMD & levels of anti-cyclic citrullinated peptide (anti-CCP) and RF in the studied cases. Patients and methods: The present study was a cross-section descriptive study that was conducted on eighty female patients with RA. All patients were subjected to assessment to the levels of anti-CCP and RF using ELISA. BMD was measured by DEXA. Results: Osteopenia and Osteoporosis at lumbar spine, femoral neck and distal end of radius showed statistically significant increase in +ve anti-CCP patients when compared to -ve anti-CCP patients. BMD at the lumbar spine, femoral neck and lower end of radius showed statistically significant decrease in +ve anti-CCP patients when compared to -ve anti-CCP patients. History of fragility fracture showed statistically significant increase in RA patients with +ve RF when compared to -ve RF patients. Conclusion: Bone loss and fragility fracture are common in RA and increased in seropositive RA, post-menopausal state and corticosteroids use. The presence of ACPA and RF are strongly predictive for the development of osteoporosis and erosions in RA patients. It would be a more appropriate approach to carefully monitor osteoporosis in seropositive RA. [ABSTRACT FROM AUTHOR]

Background: Posterior scleritis is a potentially vision threatening condition which is often underdiagnosed due to varied clinical presentation, several non-infectious inflammatory diseases can cause this disorder, although infectious diseases should be ruled out. Case presentation: A 56 years-old-female with acute unilateral decreased vision in right eye and positive history for rheumatoid arthritis (RA) was referred, based on ophthalmic examination the diagnosis of posterior scleritis was considered. The only positive inflammatory marker was found is high serum titer of Anti-Cyclic Citrullinated Peptide (Anti-CCP). Conclusion: This is the first case of posterior scleritis with only positive Anti-CCP. Elevated serum Anti-CCP titer may be considered as risk factor for inflammatory scleritis in patient with RA. [ABSTRACT FROM AUTHOR]

Protein citrullination and degradation by matrix metalloproteinases (MMP) plays a central role in the pathology of rheumatoid arthritis (RA). Autoantibodies are known to target citrullinated vimentin. The aim of this study was to investigate the relationship between the blood levels of MMP-degraded and citrullinated vimentin (VICM), as compared with the levels of MMP-degraded and non-citrullinated vimentin (VIM), and the standard anti-CCP biomarker in RA patients undergoing treatment. Thus, VIM, VICM and anti-CCP were quantified by ELISA in serum samples from baseline and week 8 of patients (n = 257) with RA, treated with either tocilizumab (8 mg/kg), methotrexate (7.5–15 mg/kg) or a placebo and compared with a reference cohort (n = 64). The three biomarkers were elevated in RA serum compared with the reference cohort: medians were 1.7 vs. 0.8 ng/mL (p < 0.05) for VIM; 7.5 vs. 0.7 ng/mL (p < 0.0001) for VICM; 57 vs. 4 RU/mL (p < 0.001) for anti-CCP. VICM was decreased in response to tocilizumab (2.9-fold, p < 0.0001) and to methotrexate (1.5-fold, p < 0.05) compared with the placebo, while anti-CCP was not. Serum VIM was also modulated by both drugs, although to a lesser degree. A high baseline level of VICM was predictive of a low disease activity response at week 8. In conclusion, VICM can differentiate between RA and healthy donors in a similar manner to anti-CCP; furthermore, VICM is also a pharmacodynamic marker. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a multifactorial disease which can be triggered by gene-environment interactions. Numerous risk factors have been acknowledged in varied ethnicities, but their generalizability is vague. Hence, proposed to identify impact of etiology on citrullination and how both interact with peptidyl arginine deiminase 4 (PADI4) polymorphism in RA onset among South Indian Tamil RA cases. Studied 207 RA cases and 186 healthy controls for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), anti-Sa (citrullinated vimentin), anti-citrullinated α-enolase peptide-1 (CEP-1) and diseases activity score-28 (DAS-28). Past exposure to studied etiological risk factors obtained through questionnaire. Family history of RA (FHRA), surgery/injury and chikungunya virus (CHIKV) infection significantly contributed to RA (p < 0.05) particularly CHIKV (OR = 6.66, 95% CI 3.92-11.32, p = 0.001). Strikingly, 67.1% of surgery/injury and 80% of CHIKV exposed patients had RA onset within a year. RA cases with tooth decay had impact on RF, anti-CCP, anti-Sa freequeny and anti-CEP-1 level (p < 0.05).Since CHIKV infected cases showed significant anti-Sa (p = 0.04) level and frequency (p = 0.01), they were genotyped for polymorphism in PADI4_92 (rs874881), 104 (rs1748033) and 94 (rs2240340) by Sanger's sequencing which demonstrated that PADI4 confers risk (p < 0.05) for the onset of CHIKV induced RA. This is the initial report that CHIKV may contribute to RA development via vimentin citrullination. FHRA, surgery/injury, CHIKV and smoking posed a key RA risk. [ABSTRACT FROM AUTHOR]

• Optical biosensors were critically reviewed, including ECL, SERS-based, and SPR-based biosensors. • Lateral flow immunoassays (LFIA) as point-of-care (POC) rapid tests were discussed. • Amperometric and label-free electrochemical biosensors developed for anti-CCP were analyzed. • The clinical significance of these biosensors and their advantages and disadvantages were demonstrated. • Various signal amplification systems with their peptide sequences and modifiers were revealed. Biosensors are unique analytical tools for the detection of biomarkers. Of these, autoantibodies against citrullinated proteins (ACPA) are useful for the differential diagnosis of rheumatoid arthritis (RA). The autoantibodies may be detected by immunoassay technology using synthetic cyclic citrullinated peptides (CCP), ie, anti-CCP. Recently, several biosensors have been developed for anti-CCP using CCP and mutated citrullinated vimentin (MCV) as recognition elements. In this review we highlight all currently available ACPA biosensor technology including those based on fluorescence, chemiluminescence, electrochemiluminescence (ECL), surface-enhanced Raman scattering (SERS)-based, surface plasmon resonance (SPR), lateral flow immunoassays (LFIA), and electrochemical. We explore various peptides as recognition elements, electrode modifiers and signal amplification systems thus providing new opportunities for next-generation biosensor design in RA. [ABSTRACT FROM AUTHOR]

Introduction : Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects small joints. The impaired chemokine and cytokine responses are essential pathological mechanisms for the RA clinical presentation. Given the role of chemokines and inflammatory reactions in RA pathogenesis, we evaluate the association between the plasma concentration of CCL20 with the clinical and laboratory parameters in newly diagnosed RA patients. Material and methods: Forty-five newly diagnosed RA patients and forty-five healthy subjects were enrolled in this study. The plasma levels of CCL20, rheumatoid factor, and anti-citrullinated peptide antibodies were measured using the enzyme-linked immunosorbent assay (ELISA) technique. Result: The plasma levels of CCL20 were increased significantly in RA patients compared to the healthy controls (p < 0.0001). There was a positive correlation between CCL20 and RF, anti-CCP, ESR, and DAS-28 (p < 0.0001, r = 0.669; p < 0.015, r = 0.358; p < 0.0001, r = 0.586; p < 0.0001, r = 0.769). Conclusion: The increased plasma levels of CCL20 in newly diagnosed RA patients may contribute to RA pathogenesis, and it is in association with clinical and laboratory parameters. Key Points • CCL20 has a contribution to the early phase of RA. [ABSTRACT FROM AUTHOR]

Objective: Autoantibodies such as rheumatoid factor, anti-nuclear antibody, anti-Ro/SSA, and anti-La/SSB have an important role in the diagnosis of primary Sjogren’s syndrome (PSS), but are not essential in seronegative PSS when there is at least one focus in minor salivary gland biopsy. The aim of this study was to compare the clinical and serological differences between patients with seropositive and seronegative PSS. Materials and Methods: The study included 273 patients with PSS who were followed up at Kayseri City Training and Research Hospital, a tertiary hospital, between June 2018 and July 2021. The diagnosis of PSS was based on the 2016 American College of Rheumatology/European League Against Rheumatism PSS classification criteria. Autoantibodies were not detected in 45 (16.5%) patients, and they were evaluated as having seronegative PSS. Clinical and laboratory parameter data of all the patients were collected retrospectively from the hospital database, and compared between the patients with seronegative PSS and patients with seropositive PSS. Results: Females constituted 93.9% (n=214) of the seropositive group and 91.1% (n=41) of the seronegative group. The mean age at diagnosis was 47.87±9.07 years in the seropositive group and 44.34±11.48 years in the seronegative group (p=0.026). No statistically significant differences were determined between the groups in terms of sex distribution, clinical features, and the rate of patients with leukopenia, lymphopenia, thrombocytopenia, hypergammaglobulinemia, hypocomplementemia, and increased acute phase reactant. The median C4 value was lower, and the median IgG value was higher in the seropositive PSS group. Conclusion: Clinical findings in patients with seronegative PSS overlapped with those of patients with seropositive PSS, but diagnosis was made later in patients with seronegative PSS. [ABSTRACT FROM AUTHOR]

Background: RA is a systemic inflammatory condition characterized by chronic arthritis and often associated with irreversible joint damage. Objectives: To assess the significance of serum level of 14-3-3η in RA and its association with clinical and serological features of the disease. Methods: This is a case-control study done on 80 participants. They were divided into 2 groups. Group 1: 40 rheumatoid arthritis patients compared to group 2: 40 healthy participants matched for age and sex. Laboratory investigations including complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPAs), and serum 14-3-3η were done to all participants. Radiological examination in the form of plain X-ray for hands and feet was done to all patients. Results: Serum levels of 14-3-3η were significantly higher in RA patients compared to the control group (p < 0.001). Serum 14-3-3η was the only predictor of high Larsen's score (p = 0.013) on using linear regression analysis. Serum 14-3-3η can predict RA in healthy controls in univariate (p = 0.001) and multivariate (p = 0.004) analyses. The receiver operating characteristic (ROC) curve of 14-3-3η was constructed for discrimination between RA and control subjects. The best cut-off value was 61.9 ng/mL, with fair AUC (0.773, p < 0.001), 95% CI (0.656–0.889), and the sensitivity and specificity of 14-3-3η for RA diagnosis as 65% and 95% respectively. Also, we constructed ROC curves for RF, ACPA, 14-3-3η, and their combinations; we found that the highest test sensitivity of 95.7% appeared on adding the 3 markers together, and the highest test specificity of 100% was detected on adding RF to ACPA, 14-3-3η to ACPA or the 3 molecules together. Conclusion: 14-3-3η could be a valuable marker for the diagnosis of RA patients and it may have prognostic value. Key Points • 14–3-3η is a valuable marker for the diagnosis of RA patients. • 14–3-3η reflects disease severity and joint damage in RA patients. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are known to have an important role in triggering the innate immune response and in priming antigen-specific adaptive immunity and inflammation. The differences in synovial tissue expression of the TLRs between seronegative and seropositive rheumatoid arthritis (RA) were examined from 9 seropositive RA, 5 seronegative RA and 4 osteoarthritis (OA) patients. Synovitis status was assessed using Krenn's scoring and TLR 1–9 expression by immunohistochemistry. Tissue citrulline content was analysed by HPLC method. In RA TLR expression was generally higher than in OA. TLR2 expression was higher in both seronegative and seropositive RA compared to OA. TLR 1, 4 and 8 expressions were higher in seropositive RA than in seronegative RA or in OA. For TLRs 3, 5, 6, 7 and 9 local differences of expression were found between groups. TLR 1–9 expression correlated with the synovitis grade. No statistical difference was found in synovial tissue citrulline content between the groups. In seropositive RA, the TLR repertoire in the synovial tissue differs from seronegative RA and could explain differences in disease outcomes. The high expression of protein sensing (TLR1, TLR2 and TLR4) and nucleic acid sensing TLRs (TLR7, TLR8 and TLR9) in the seropositive RA could make the synovium primed for reacting to citrullinated proteins and nucleic acids that could be released to extracellular space in formation of neutrophil extracellular traps. This reactivity could be augmented by Fc receptor activation by anti-citrullinated protein antibody immunocomplexes associated with seropositive RA. [ABSTRACT FROM AUTHOR]

Aim: To investigate anti‐cyclic citrullinated peptide (anti‐CCP) and rheumatoid factor (RF) in relation to ultrasound‐detected joint inflammation and bone erosion in patients with rheumatoid arthritis (RA) as previous studies have mainly utilized radiographic damage as imaging outcomes. Method: In this cross‐sectional study, patients were grouped based on their Disease Activity Score at 28 joints (DAS28 < 3.2, DAS28 ≥ 3.2). Ultrasound variables (power Doppler and gray scale joint inflammation graded 0‐3 semi‐quantitatively; bone erosion graded Yes = 1/No = 0 dichotomously) were correlated with antibodies levels using Pearson correlation. Simple linear regression was used to characterize relationships between variables. Receiver operating characteristic (ROC) analysis was performed to determine statistically optimal cut‐off values for identifying patient subgroups with ultrasound erosion scores >25th, >50th and >75th percentiles. Results: One thousand and eighty joints and 1800 joint recesses from 36 peripheral joint sites were scanned in 30 adult RA patients (mean disease duration, 70.3 months; 93.3% female; 93.3% anti‐CCP positive; 93.3% RF positive). In the DAS28 < 3.2 group, no significant correlations were found between antibody levels and ultrasound variables. In the DAS28 ≥ 3.2 group, anti‐CCP levels correlated significantly (r = 0.46, P =.048) and were predictive (P =.048) of ultrasound erosion scores. Area under the ROC curve based on cut‐off anti‐CCP level of ≥95.2 to identify patients with ultrasound erosion scores >7 (75th percentile) was 0.72 (sensitivity = 83.3%, specificity = 53.8%). Conclusion: The association of anti‐CCP and RF with joint damage appears to differ in RA. Among patients with at least moderate disease activity (DAS28 ≥ 3.2), anti‐CCP—but not RF—is associated with joint damage, being moderately correlated with ultrasound‐detected bone erosion. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is an autoimmune disorder that is highly prevalent, leading to gradual cartilage distraction, and therefore is important to diagnose in the early stage. This study aimed to estimate the level of rheumatoid factor (RF) and Anticitrullinated protein (Anti-ccp) in the serum of female patients. We also investigated several female reproductive hormones in the patients and compared their levels in the premenopausal and postmenopausal phases. The study included 88 female subjects, 50 suffering from signs of rheumatoid arthritis who were attending ALYarmouk teaching hospital, Baghdad, Iraq, and 38 without clinical signs of RA as a control group. The ELISA technique was used to estimate all the studied parameters. The results showed a significant elevation in the levels of RF (103.6 ± 227.0 vs. 22.1 ± 111.0 U/ml) and Anti-ccp (158.0 ± 170.0 vs. 0.51 ± 1.69 U/ml) in patient’s serum as compared to the control. The percentage of overweight and obese patients was higher than that of those with normal weight. Also, the current results showed significant differences in the serum concentrations of the reproductive hormones between the premenopausal and postmenopausal phases in the patients group. The level of FSH in postmenopausal female patients was higher than that in premenopausal ones (33.5 ± 17.9 vs. 9.01 ± 9.31 U/ml). Also, the level of luteinizing hormone (LH) in the postmenopausal patients was higher than that in the premenopausal patients (26.4 ± 12.3 vs. 12.7 ± 10.2 U/ml). While the level of prolactin (PRL) in RA postmenopausal female patients was lower than that in the premenopausal patients (8.60 ± 7.07 vs. 14.8 ± 10.6 ng/ml). In addition, the level of Anti-mullerian hormone (AMH) in post-menopausal patients was lower than that in the pre-menopausal ones (0.034 ± 0.023 vs. 0.635 ± 0.683 ng/ml). Finally, the concentration of estradiol (E2) in the post-menopausal female patients was lower than that in the pre-menopausal ones (32.9 ± 18.6 vs. 76.5 ± 43.6 ng/ml). [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity. Methodology: This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI). Results: The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices. Conclusions: Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points • IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. • RF, anti-CCP, and anti-MCV had higher levels in early than established RA. • IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. • Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic T cell-mediated autoimmune disease. Serum autoantibodies against cyclic citrullinated peptides (anti-CCP) are significant markers for diagnosis and prognosis of this disease. Induction of immune tolerance as therapeutic approach for RA constitutes a current research focal point. In this sense, we carried out a phase I clinical trial in RA patients with a new therapeutic candidate (called CIGB-814); which induced mechanisms associated with restoration of peripheral tolerance in preclinical studies. CIGB 814 is an altered peptide ligand (APL), derived from a CD4+ T cell epitope of human heat-shock protein 60 (HSP60), an autoantigen involved in the pathogenesis of RA. Twenty patients with moderate disease activity were included in this open label trial. Sequential dose-escalation of 1, 2.5 and 5 mg of CIGB-814 was studied. Consecutive groups of six, five, and nine patients received a subcutaneous dose weekly of the peptide during the first month and one dose monthly during the next 5 months. The peptide was well tolerated and reduced disease activity. Here, we reported the quantification of anti-CCP antibodies during the treatment with this APL and in the follow-up stage. Anti-CCP antibodies were quantified in the plasma from patients by a commercial enzyme immunoassay at baseline (T0) and at weeks 28 and 48. Results showed that CIGB-814 induced a significant reduction of anti-CCP antibodies. In addition, this decrease correlated with clinical improvement in patients assessed by Disease Activity Score in 28 joints (DAS28) criteria. These findings reinforce the therapeutic potential of CIGB-814. [ABSTRACT FROM AUTHOR]

Objectives The development of RA includes a phase of arthralgia preceding clinical arthritis. The aetiology of symptoms of arthralgia is unclear. Since subclinical joint inflammation is expected to be causally related to pain, we aimed to study associations between subclinical MRI-detected inflammation and pain in patients with arthralgia suspicious for progression to RA. Methods Unilateral MRIs of the wrist, MCP (2–5) and MTP (1–5) joints of 325 patients who fulfilled the EULAR definition of arthralgia suspicious for progression to RA were scored by two readers on subclinical inflammation (synovitis, bone marrow oedema and tenosynovitis). Associations between MRI-detected inflammation and overall pain severity at patient level (measured using the visual analogue scale), as well as with local joint tenderness, were studied. Analyses were stratified for ACPA. Results At patient level, synovitis (β = 0.10, P = 0.048) and tenosynovitis (β = 0.11, P = 0.026) associated with the visual analogue scale pain. Of the 1620 imaged joints, 447 (28%) were tender. MRI-detected synovitis associated independently with joint tenderness in all patients (odds ratio 1.74, P < 0.001), and in the ACPA-negative stratum (odds ratio 1.96, P < 0.001). In the ACPA-positive stratum only bone marrow oedema (osteitis) was independently associated with tenderness (odds ratio 2.39, P = 0.005). Sensitivity analyses in patients who developed inflammatory arthritis during follow-up (n = 61) revealed similar associations. Subclinical inflammation was present in 51% of tender joints and 39% of non-tender joints. Conclusion In patients with arthralgia suspicious for progression to RA, MRI-detected subclinical inflammation is associated with overall pain and local joint tenderness. However, the association is partial, indicating that subclinical inflammation is not the sole explanation of the arthralgia. [ABSTRACT FROM AUTHOR]

Abstract Background We studied the relationship between serum lipids and autoantibodies and inflammatory markers in rheumatoid arthritis (RA) patients to explore the effect of serum lipids on the diagnosis and judgment of disease activity in RA patients. Methods Serum lipids including TCHO, TG, HDLC and LDLC and anti-CCP, RF, CRP, ESR of RA patients from May 2013 to August 2017 were retrospectively analyzed in the First Affiliated Hospital of Fujian Medical University. Results With the dilution factor increased, the concentrations of serum lipids and anti-CCP, CRP and RF showed the same downward trend, indicating that the detection methods of the above indicators were reasonable and would not be affected by hyperlipidemia. CRP and ESR levels were negatively correlated with HDLC concentration in male and female RA patients. However, the concentration of anti-CCP and RF were closely related to TG. In all the RA patients and female RA patients, the RF level was negatively correlated with the TG concentration. Moreover, with the TG concentration increased, the proportion of patients with high concentrations of anti-CCP levels decreased. In addition, in male RA patients, anti-CCP and ESR concentration increased with the increase of LDLC. Conclusion The concentrations of HDLC, TG and LDLC were associated with the concentration of anti-CCP, RF, CRP and ESR in RA patients. Therefore, clinical diagnosis of RA and determination of disease activity should consider the impact of the concentration of serum lipids in order to make a reasonable judgment on the diagnosis of the disease. Highlights • CRP and ESR were negatively correlated with HDLC in RA patients. • RF was negatively correlated with TG in female RA patients. • Anti-CCP and ESR increased with the increase of LDLC in male RA patients. • Diagnosis of RA should consider the impact of the concentration of serum lipids. [ABSTRACT FROM AUTHOR]

Anti-cyclic citrullinated peptide antibodies (anti-CCPs) are important diagnostic markers for rheumatoid arthritis (RA). We evaluated the analytical and clinical performance of the QUANTA Flash CCP3 (INOVA Diagnostics, USA), a fully automated third-generation anti-CCP assay, in comparison with three second-generation anti-CCP (CCP2) assays. A total of 300 sera (67 from RA patients, 64 from other rheumatic diseases, 43 from osteoarthritis [OA], and 126 from other conditions) were tested with QUANTA Flash CCP3, Kallestad Anti-CCP II (Bio-Rad, USA), Elecsys Anti-CCP (Roche Diagnostics GmbH, Germany), and ARCHITECT Anti-CCP (Abbott Diagnostics, USA). Within-run and total imprecision (% coefficient of variation) of the QUANTA Flash CCP3 were <6%, and its linearity was acceptable over the claimed range (4.0-2,749.7 chemiluminescent units). The frequency of anti-CCP was similar between QUANTA Flash CCP3 and the other CCP2 assays in the RA (67.2% vs. 62.7-70.1%), other rheumatic diseases (7.8% vs. 6.3%), and OA (2.3% vs. 0-2.3%) groups. The concordance rate between QUANTA Flash CCP3 and the other assays ranged from 96.3% to 97.7% (kappa from 0.87 to 0.92). For the diagnosis of RA, the sensitivity/specificity was 67.2%/95.7%, 62.7%/98.3%, 70.2%/96.6%, and 67.2%/97.9%, and the areas under the receiver operating characteristic curves were 0.851, 0.791, 0.853, and 0.867 for QUANTA Flash CCP3, Kallestad, Elecsys, and ARCHITECT assays, respectively. The performance of the QUANTA Flash CCP3 was satisfactory and comparable to that of the three CCP2 assays. This fully automated assay would be a practical and reasonable option in clinical laboratories. [ABSTRACT FROM AUTHOR]

Background: The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis. Falsely elevated anti-CCP IgG antibodies due to anti-streptavidin IgG antibodies were suspected in our laboratory. Methods: In this study, we evaluated, in a standardized approach, the prevalence of anti-streptavidin IgG antibodies in a primary care setting and the effect of anti-streptavidin IgG antibodies on anti-CCP IgG assays from three different important commercial manufacturers (Abbott, Roche Diagnostics, Thermo Fisher Scientific). Three different populations were consecutively and prospectively studied: serum samples from 1000 ambulatory patients, 286 serum samples from patients for which anti-CCP was requested and 89 serum samples from patients which had previously given a positive anti-CCP result on Architect® i2000. Results: The frequency of confirmed anti-streptavidin IgG-positive samples detected in this study was 0.6% (8/1375). Anti-CCP IgG was determined on the eight samples with confirmed anti-streptavidin IgG antibodies: with the Cobas® method, seven positive anti-CCP results were observed and five positive anti-CCP results with the Architect® method. No positive anti-CCP IgG results were obtained with the EliA™ method. Rheumatoid factor was negative in these eight samples. Conclusions: Anti-streptavidin IgG antibodies rarely cause false-positive results in some anti-CCP assays. However, despite being an infrequent assay problem, it could possibly lead to diagnostic confusion or even an incorrect diagnosis of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

HLA-II molecules are critical in triggering human immune response, especially in activating CD4+ T cells. HLA-DP, belonging to HLA-II molecules, draws increasing attention for its role in presentation of viral antigen and autoantigen to T cells. Researches reported single nucleotide polymorphism (SNP) of HLA-DP associated with HBV infection and autoimmune diseases such as SLE. However, little is known about the relationship between HLA-DP and rheumatoid arthritis (RA). Rs9277535 is located in 3′ UTR region of HLA-DPB1, a subunit of HLA-DP, and was reported to affect HLA-DP mRNA expression. In the present study, we explored the relationship between gene polymorphism of rs9277535 in HLA-DPB1 and RA susceptibility and progression. Samples from 254 patients with RA and 391 age- and sex-matched healthy controls were collected and genotyped by a polymerase chain reaction-high-resolution melting (PCR-HRM) assay. Serological tests (anti-CCP, rheumatoid factor, C-reactive protein, anti-keratin antibody) were detected by laboratory assays. Strong association was observed between SNP rs9277535 in HLA-DP and RA susceptibility (allele frequency distribution: OR = 1.409, 95%CI = 1.121-1.773, P = 0.004). Further validation was provided by disease model analysis (recessive model: OR = 1.889, 95%CI = 1.194-2.990, P = 0.008; dominant model: OR = 1.464, 95%CI = 1.050-2.041, P = 0.025; additive model: OR = 2.208, 95%CI = 1.335-3.652, P = 0.003). Allele A was correlated to increased risk of RA. Serological test results demonstrated patients carrying allele A of rs9277535 had elevated serum anti-CCP antibody level. The present study provided evidence that HLA-DP gene polymorphism associated with RA susceptibility. Allele A of rs9277535 in HLA-DP correlated to increased risk of RA and elevated serum anti-CCP level. [ABSTRACT FROM AUTHOR]

Purpose: A retrospective comparison of the prevalence and diagnostic value of anti-Sa, anti-CEP-1, and anti-MCV autoantibodies relative to those of the established autoantibodies, composite RF and anti-CCP-IgG used routinely for RA diagnosis as a component of the ACR 2010 criteria, in a cohort of disease-modifying anti-rheumatic drug naïve African RA patients (n = 75).Methods: Serum concentrations of anti-Sa, anti-CEP-1 and anti-MCV autoantibodies were measured using ELISA procedures, while anti-CCP-IgG antibodies were determined by fluorescence enzyme immunoassay, and composite RF by latex-enhanced laser nephelometry.Results: The seropositivity frequencies of anti-Sa, anti-CEP-1 and anti-MCV antibodies for the RA patients were 82, 72, 85%, respectively, while that of anti-CCP-IgG and RF was 87% for both. Overall, anti-MCV demonstrated the best specificity, positive predictive value (PPV), odds ratio and positive likelihood ratio of all the types of autoantibody tested.Conclusion: These observations in this unique cohort of RA patients indicated novel associations of all three autoantibodies in regard to HLA-SE risk alleles, disease severity and tobacco use that were not reported before. Elevated anti-Sa titers designated a propensity of higher disease and high-risk alleles in our cohort. Anti-CEP-1 association with HLA-SE homozygosity and high-risk alleles is also novel in this group. Of note, measurement of anti-MCV antibodies on presentation, either as an adjunctive or even as a stand-alone test, surpassed all other biomarkers investigated here and, therefore, may add value to clinical management. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of calreticulin and its correlation with autoantibodies and inflammatory cytokines in patients with early rheumatoid arthritis (RA). Methods Serum samples were obtained from 106 patients with early active RA, 95 patients with stable RA, 85 osteoarthritis (OA) and 80 healthy controls (HC). Serum levels of calreticulin, anti- cyclic peptide antibody (CCP), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immnuosorbent assay (ELISA). The serum level of rheumatoid factor (RF) was detected by immunoturbidimetry. The correlations between serum calreticulin and inflammatory cytokines were evaluated using Spearman’s rank correlation test. Results Serum levels of calreticulin were significantly higher in patients with early active RA [(5.84±2.62) μg/L] than those in patients with stable RA [(4.26±1.42) μg/L], patients with OA [(3.92±1.10) μg/L] and HC [(3.86±0.91) μg/L] (P<0.001). There were no statistical differences in serum levels of calreticulin between stable RA, OA and HC groups (P>0.05). Serum levels of calreticulin were significantly higher in RF-positive RA patients than those of RF-negative RA patients [(6.12±2.87) μg/L vs. (4.92±1.22) μg/L, P=0.045]. Serum calreticulin levels were also significantly higher in anti-CCP-positive RA patients than those of anti-CCP-negative RA patients [(6.39±2.93) μg/L vs. (4.69±1.17) μg/L, P=0.002]. The serum level of calreticulin was positively correlated with IL-1β (rs=0.386, P=0.009), IL-6 (rs=0.405, P=0.006) and TNF-α (rs=0.428, P=0.003) in early active RA patients. Conclusion The elevated serum level of calreticulin is related to autoantibodies and inflammatory cytokines in early RA patients, suggesting that calreticulin can be used as a potential biomarker for early diagnosis and prognosis of RA. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Patients with rheumatoid arthritis (RA) and co‐existent bronchiectasis (BRRA) have a five‐fold increased mortality compared to rheumatoid arthritis alone. Yet previous studies have found no difference in clinical and serological markers of RA disease severity between BRRA patients and RA alone. However, RA disease activity measures such as Disease Activity Score of 28 joints – C‐reactive protein (DAS28‐CRP) and anti‐cyclic citrullinated peptide antibodies (anti‐CCP) have not been studied, so we assessed these parameters in patients with BRRA and RA alone. Methods: BRRA patients (n = 53) had high‐resolution computed tomography proven bronchiectasis without any interstitial lung disease and ≥ 2 respiratory infections/year. RA alone patients (n = 50) had no clinical or radiological evidence of lung disease. DAS28‐CRP, rheumatoid factor (immunoglobulin M) and anti‐CCP were measured in all patients, together with detailed clinical and radiology records. Results: In BRRA, bronchiectasis predated RA in 58% of patients. BRRA patients had higher DAS28 scores (3.51 vs. 2.59), higher levels of anti‐CCP (89% vs. 46%) and rheumatoid factor (79% vs. 52%) (P = 0.003) compared to RA alone. Where hand and foot radiology findings were recorded, 29/37 BRRA (78%) and 13/30 (43%) RA alone had evidence of erosive change (P = 0.003). There were no significant differences between groups in smoking history or disease‐modifying anti‐rheumatic drug/biologic therapy. Conclusions: Increased levels of RA disease activity, severity and RA autoantibodies are demonstrated in patients with RA and co‐existent bronchiectasis compared to patients with RA alone, despite lower tobacco exposure. This study demonstrates that BRRA is a more severe systemic disease than RA alone. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls. STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the TaqMan allelic discrimination method. The frequency of STAT4 variant allele was significantly higher in RA patients than in controls ( p = 0.01), while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The frequency of STAT4 variant allele carrier genotypes (GT+TT) was significantly higher among RA patients than in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and dominant models. The frequency of RF and anti-CCP positivity was significantly higher among RA patients carrying T allele genotypes compared to patients carrying wild genotype ( P = 0.02 and 0.04, respectively). No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. Our study confirmed the association of STAT4 rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small non-coding RNAs, whose role in regulating diverse immune functions, suggests they might play a role as biomarkers for immune mediated disorders. Studies showed that miRNA-146a (miR-146a) expression is increased by proinflammatory cytokines and is an important modulator of differentiation and function of cells of innate and adaptive immunity. Aim of the work: The current study aimed to evaluate the expression of miR-146a as a potential biomarker for diagnosis of rheumatoid arthritis (RA) and to explore its association with disease activity. Subjects and methods: The study enrolled 50 Egyptian subjects divided into a patient group, which comprised 25 RA patients, and a control group which comprised 25 healthy individuals. The disease activity for the patients' group was determined by simplified disease activity index. Relative quantification of miR-146a expression in whole blood was determined using reverse transcriptase quantitative real time polymerase chain reaction. Results: There were highly significant statistical differences between patients and healthy controls as regards miR-146a relative expression, erythrocyte sedimentation rate (ESR) and anticyclic citrullinated peptide (anti-CCP) (p< 0.001). Highly significant statistical differences (p< 0.001) were also found between different patients' subgroups as regards miR-146a relative expression and ESR. miR-146a levels correlated positively with those of ESR, C-reactive protein and anti-CCP (p< 0.001). miR-146a illustrated best performance in diagnosing RA, showing the highest sensitivity and specificity (96% and 100%, respectively) (AUC: 0.992 at a cut off value of P2.16) compared to anti-CCP (sensitivity: 68%, specificity: 100% and AUC: 0.87 at a cut off value of P22 U/ml) and RF (sensitivity: 56%, specificity: 80% and AUC: 0.992 at a cut off value of P13 U/ml). [ABSTRACT FROM AUTHOR]

A majority of circulating IgG is produced by plasma cells residing in the bone marrow (BM). Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA− using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1 , JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. For three patients, we identified clonotypes shared between BM plasma cells and PB memory B cells. Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. ACPA-producing BM plasma cells were identified in two ACPA+ patients. Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. Out of these, two clones reacted with citrullinated histone-4 and activated neutrophils. In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. • Paired heavy-light chain repertoires reveal plasma cell clonal relationships. • Shared blood memory and bone marrow plasma cell clonotypes were identified. • N-linked glycosylation sites were common in the RA IgG + plasma cells. • RA patients demonstrated differences in plasma cell IgA/IgG ratio and IgG4 usage. • Different single-cell methods identified RA ACPA-producing bone marrow plasma cells. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Serologically, it can be differentiated according to rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), or both. This differentiation is prognostically and therapeutically relevant. No method has been described to separate the two forms phenotypically. We hypothesize that a differentiation is possible by evaluating oscillation patterns in power Doppler sonography (PDS). In a prospective study, 20 patients with anti-CCP-positive RA and 20 patients with anti-CCP-negative RA with active wrist synovitis were examined. A PDS scan was performed, and perfusion maxima ( P ) and minima ( P ) as well as the amplitude (Δ P) were determined by a blinded study member. The amplitude was standardized (sΔ P) by dividing by P , and the anti-CCP-positive and anti-CCP-negative patients as well as the RF-positive and RF-negative were compared to each other. In the ultrasonographic evaluation, we found a highly significant difference in sΔ P between CCPp and CCPn patients (median 19.0 vs. 42.9 %, p < 0.0001). sΔ P is independent of disease activity. The absolute amplitude Δ P did not differ between the groups. Also, in anti-CCP-positive patients there was a completely linear correlation between P and P , and this was far less marked in anti-CCP-negative patients. Anti-CCP-positive and anti-CCP-negative RA display different PDS oscillation patterns. This constitutes a nonserological parameter to differentiate between the two forms. The difference in PDS oscillation patterns suggests that the underlying pathological process differs between the forms. [ABSTRACT FROM AUTHOR]

Epidemiological studies have linked periodontitis to rheumatoid arthritis (RA). Porphyromonas gingivalis (Pg) was reported recently to produce citrullinated protein (CP) and increase anti-cyclic CP antibody (ACPA), both of which have been identified as causative factors of RA. In the present study, we determined the effects of Pg infection on the exacerbation of RA in a mouse model. RA model mice (SKG mice) were established by an intraperitoneal (i.p.) injection of laminarin (LA). Mice were divided into six groups, Ctrl (PBS injection), LA (LA injection), Pg/LA (Pg + LA injection), Pg (Pg injection), Ec/LA ( Escherichia coli and LA injection) and Ec ( E. coli injection). In order to evaluate RA, joint swelling by the arthritis score, bone morphology by microcomputed tomography (microCT), haematoxylin and eosin staining, ACPA, matrix metalloproteinase-3 (MMP-3) and cytokine level in serum by enzyme-linked immunosorbent assay were determined. Osteoclast differentiation from bone marrow mononuclear cells (BMCs) was examined to clarify the underlying mechanisms of RA. The presence of Pg and CP in joint tissue was also investigated. The arthritis score was threefold higher in the Pg/LA group than in the LA group. Severe bone destruction was observed in joint tissue of the Pg/LA group. A microCT analysis of the Pg/LA group revealed a decrease in bone density. ACPA, MMP-3, interleukin (IL)-2, IL-6, CXCL1 and macrophage inflammatory protein (MIP)-1α levels from the Pg/LA group were the highest. The osteoclastogenesis of BMCs was enhanced in the Pg/LA group. Furthermore, large amounts of Pg components and CP were detected in the Pg/LA group. In conclusion, Pg infection has the potential to exacerbate RA. [ABSTRACT FROM AUTHOR]

Otoimmün ve sistemik bir hastalık olan romatoid artritte (RA) akciğer tutulumu oldukça sık görülmektedir. Olgumuz elli sekiz yaşında kadın hasta, nefes darlığı, mide ve yaygın eklem ağrısı nedeniyle incelenmişti. Akciğer grafisinde iki taraflı pulmoner nodül ve plevral efüzyon saptanan hasta metastatik akciğer kanseri ön tanısı ile kliniğimize gönderildi. Laboratuvar değerlendirmesinde anemi, C-reaktif protein ve sedimentasyon yüksekliği saptandı. Torasentez yapıldı, plevral sıvı eksuda karakterindeydi. Glukoz düşük, adenozin deaminaz ve laktat dehidrogenaz yüksekti. Eklem ağrıları nedeniyle bakılan kan ve plevra romatoid faktör yüksek saptandı. Kanda bakılan anti-siklik sitrüline peptitin pozitif idi. Hasta romatoloji ile konsulte edildi, bu bulgularla RA ve akciğer tutulumu tanısı kondu. Metilprednizolon tedavisi ile plevral efüzyonu ve nodülleri kayboldu. Bu olgu iki taraflı pulmoner nodül ve plevral efüzyonun ayırıcı tanısında, önceden bilinen RA tanısı olmasa dahi bu hastalığın akılda tutulması gerektiğini vurgulamak amacıyla sunuldu. Rheumatoid arthritis (RA), as a systemic autoimmune disease, frequently features pulmonary involvement. A 58-year-old woman was examined due to shortness of breath, stomach ache, and arthralgia. Pleural effusion and bilateral pulmonary nodules were observed on chest X-ray, and patient was sent to our hospital with initial diagnosis of metastatic lung cancer. C-reactive protein level and sedimentation rate test results were elevated. Thoracentesis was performed, and pleural effusion was found to be exudative. Low glucose and high adenosine deaminase and lactate dehydrogenase levels were detected. Blood and pleural fluid rheumatoid factor levels measured because of the presence of arthralgia were found to be high. High blood anti-cyclic citrullinated peptide levels were also detected. After consultation with department of rheumatology, patient was diagnosed as RA with pulmonary involvement. Pleural effusion and nodules resolved after treatment with methylprednisolone. This case was presented to emphasize that RA should be kept in mind in differential diagnosis of bilateral pulmonary nodules and pleural effusion. [ABSTRACT FROM AUTHOR]

Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA. [ABSTRACT FROM AUTHOR]

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

Objective. To investigate whether subfamilies of the RA-specific autoantibodies to human citrullinated fibrinogen (AhFibA) differentially associate with the RA risk factors, HLA-DRB1 shared epitope containing alleles (SE alleles) and cigarette smoking, and thus help to predict the disease outcome. Methods. AhFibA and their anti-α36-50Cit and anti-β60-74Cit subfamilies were assayed by ELISA, at baseline, in the French ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) cohort composed of undifferentiated arthritides and RA patients of <6 months' duration. Cigarette smoking, SE alleles' presence, DAS28, HAQ and modified Sharp-van der Heijde Score data were obtained at baseline, and after follow-up. Results. After 3 years, 701 patients were classified as having RA according to the ACR/EULAR 2010 criteria. Among them, 349 (50%), 203 (29%) and 257 (37%) were AhFibA-, anti-α36-50Cit- and anti-β60-74Cit-positive, respectively. The presence and titres of AhFibA and their subfamilies similarly associated with SE alleles, irrespective of their fine specificity, without significant effect of smoking. Neither their presence nor their titre was associated with DAS28 or HAQ. The presence of at least one subfamily was associated with a faster Sharp/van der Heijde score progression, albeit without correlation with the titre. Conclusion. AhFibA and their main subfamilies are similarly associated with SE alleles without additional effect of smoking. Whatever their fine specificity was, their presence (but not their titre) similarly constituted a marker of faster joint destruction. [ABSTRACT FROM AUTHOR]

Surface plasmon resonance (SPR) sensors have been used for detection of various biomolecules because of their simplicity, high specificity and sensitivity, real-time detection, low cost, and no requirement of labeling. Recently, molecularly imprinted polymers that are easy to prepare, less expensive, stable, have talent for molecular recognition and also are used for creation selective binding sites for target molecule on the SPR sensors. Here, we show that preparation of cyclic citrullinated peptide antibody (anti-CCP) imprinted SPR sensor to detect CCP antibodies. For this purpose, anti-CCP/AAm pre-complex was synthesized by interacting acrylamide (AAm) monomer with anti-CCP. Then, anti-CCP imprinted (anti-CCP/PAAm) SPR sensor was obtained by reacting with anti-CCP/AAm pre-complex in the presence of the crosslinker, and initiator/activator pair. Besides this, non-imprinted (PAAm) SPR sensor was also prepared without using anti-CCP template. The SPR sensors were characterized and then adsorption-desorption studies were performed with pH 7.0 phosphate buffer (10 mM) and acetic acid (10%) with Tween 20 (1%) in pH 7.0 phosphate buffer. Selectivitiy of sensors was investigated by using immunoglobulin M (IgM) and bovine serum albumin (BSA). To determine the adsorption model of interactions between anti-CCP solutions and anti-CCP/PAAm SPR sensor, different adsorption models were performed. The calculated maximum reflection, detection limit, association and dissociation constants were 1.079 RU/mL, 0.177 RU/mL, 0.589 RU/mL and 1.697 mL/RU, respectively. Repeatability experiments of anti-CCP/PAAm SPR sensor was performed four times with adsorption-desorption-regeneration cycles without any performance losing. Results showed that anti-CCP/PAAm SPR sensor had high selectivity and sensitivity for detection of CCP antibodies. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected disease in tropical countries. Clinical and laboratory features may mimic autoimmune diseases and this can complicate the Leishmania diagnosis. Due to our previous investigation for false anti-CCP2 reactivity in Leishmania -infected subjects and our interest in immunity against the joint-specific collagen type II (CII) in rheumatoid arthritis (RA) we investigated the same cohort for anti-CII antibodies. We found elevated anti-CII reactivity in Leishmania -infected patients as compared to controls. When anti-CII OD values were compared with BSA-blocked control plates we found higher reactivity against BSA than in CII-coated plates in many Leishmania -infected patients. The percentage of such false positive anti-CII reactions increased with inflammatory activity, and was found in almost all Leishmania patients with highly active inflammatory disease, but was as low in Sudanese healthy controls as well as among Swedish RA patients. The correlation coefficients between false positive anti-CII and anti-CCP2 measured with a commercial ELISA were highest for patients with the most inflammatory disease but non-significant for Sudanese controls and Swedish RA patients, arguing that our findings may have general implications for ELISA measurements in leishmaniasis. ELISA investigations in areas endemic for leishmaniasis might benefit from individual-specific control wells for each serum sample. This approach might also be applicable to other geographical areas or patient groups with high incidence of inflammatory and infectious diseases. [ABSTRACT FROM AUTHOR]

We assessed the clinical feasibility of conducting immunoassays based on surface-enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group ( n = 31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group ( n = 43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA. [ABSTRACT FROM AUTHOR]

Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz ., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor- α (TNF- α ), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF- α , IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The genes encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) and signal transducer and activator of transcription 4 (STAT4) have been reported to be associated with RA in several ethnic populations. Objectives: This work aims to assess the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility through an updated meta-analysis of available case-control studies. Methods: A literature search of all relevant studies published from January 2007 up to December 2014 was conducted using Pubmed and Science Direct databases. The observed studies that were related to an association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility were identified. Meta-analyis of the pooled and stratified data was done and assessed using varied genetic models. Results: Thirty-seven case-control studies with a total of 47 comparisons (29 for PTPN22 rs2476601 polymorphism and 18 for STAT4 rs7574865 polymorphism) met our inclusion criteria. The meta-analysis showed an association between PTPN22 T allele, CT+TT and TT genotypes with RA susceptibility. Furthermore, The meta-analysis showed an association between STAT4 T allele, GT+TT and TT genotypes with RA susceptibility. Stratification of RA patients according to ethnic groups showed that PTPN22 T allele, CT+TT genotypes, STAT4 T allele and STAT4 GT+TT were significantly associated with RA in European, Asian, African subjects, while PTPN22 TT genotype was significantly associated with RA in European but not in Asian and African subjects and STAT4 TT genotype was significantly associated with RA in European and Asian but not in African subject. A subgroup analysis according to the presence or absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility may not be dependent on RF and anti-CCP antibodies. Conclusions: Our meta-analysis demonstrated that PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms confers susceptibility to RA in total subjects and in major ethnic groups. The association may not be dependent on RF and anti-CCP antibodies. [ABSTRACT FROM AUTHOR]

Background/Aims: Arthropathy is the most common extraintestinal manifestation observed in patients with Crohn's disease (CD). The present study aimed to screen rheumatoid arthritis (RA) using anti-CCP antibodies and rheumatoid factor (RF) in CD patients from Southern Brazil. Additionally, the presence of arthralgia and spondyloarthritis (SpA) was evaluated. CD patients, previously diagnosed using clinical data, imaging tests, endoscopic and histological findings, were included consecutively. Methods: A total of 100 patients participated in the study, of which 60% were female, with a mean age of 41.9 ± 12.04 (16-83 years). As controls, sera from 100 healthy individuals from the same geographic area were analyzed. Results: Arthralgias were present in 55% of the patients, being more frequent in women (65.5%; 36/55), than in males (34.5%). No association was found between arthralgia and the treatment method used. Six patients (6/100) had SpA previously diagnosed. In the CD group, anti-CCP was positive only in one patient, while RF was positive in 7 patients (7%; 7/100). The anti-CCP positive patient (woman, 38 years old, RF positive), fulfilled the ACR criteria and was diagnosed as RA. In the control group, anti-CCP antibodies were detected in 1% (1/100) and RF was positive in 6 of the samples (6%). Conclusion: Our data showed low frequency of anti-CCP antibodies and RF in Brazilian patients with CD. Additionally, we found a high prevalence of arthralgia in these patients, with 6% of them diagnosed with SpA. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background The gene encoding cytotoxic T lymphocyte associated antigen-4 ( CTLA-4 ) has been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The aim of this work is to assess the association of this polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. Subjects and methods This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy controls from the same locality. For all subjects, DNA was genotyped for CTLA-4 + 49 A>G ( rs231775 ) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results The frequency of the CTLA-4 G allele was significantly higher among cases compared to controls (37.1% vs. 23.4%, OR = 1.93; 95% CI = 1.29–2.89, p = 0.002). Also, the frequency of CTLA-4 + 49 G allele carriage ( AG+GG genotypes) was significantly higher among cases with RA compared to controls (61.6% vs. 41.8%, OR = 2.23, 95% CI = 1.32–3.77, p = 0.003). Logistic regression analysis showed that cases positive to the G allele ( GA+GG genotypes) had less frequency of rheumatoid deformities and also a lower DAS28-CRP score, yet with a higher visual analogue scale (VAS) i.e. more functional disability than other cases. Conclusions CTLA-4 + 49 G allele carriage was associated with increased susceptibility and functional disability of RA in Egyptian patients. [ABSTRACT FROM AUTHOR]

Aim To evaluate the prevalence and diagnostic significance of the autoantibody against citrullinated vimentin (anti-Sa) compared with the widely used anti-cyclic citrullinated peptide autoantibody (anti- CCP) in patients with rheumatoid arthritis ( RA). Method One hundred and sixty-nine patients hospitalized at the Department of Rheumatology and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland, were enrolled in a cross-sectional study and divided into two groups. The RA group comprised 41 patients diagnosed as having RA. The non- RA control group included 128 individuals with a variety of rheumatic disorders. Serum anti-Sa and anti- CCP measurements were performed by enzyme-linked immunosorbent assay. Results The sensitivity and specificity of anti-Sa for the diagnosis of RA was 36.6% and 96.9%, respectively. For the anti- CCP test, the sensitivity was 65.9% and the specificity was 95.3%. Concomitant presence of anti-Sa and anti- CCP was determined in 36.6% of the patients with RA, whereas isolated positivity of anti-Sa was not observed. Anti-Sa positive RA patients had significantly higher anti- CCP levels compared to anti-Sa negative subjects ( P < 0.05). Conclusion With regard to the relatively low diagnostic sensitivity and the lack of cases identified by anti-Sa alone, we were unable to demonstrate any additional diagnostic value of the anti-Sa autoantibody in comparison to the anti- CCP autoantibody. To the authors' best knowledge, this is the first study among Polish patients verifying the clinical utility of anti-Sa in the diagnosis of RA. [ABSTRACT FROM AUTHOR]

Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group ( p = 0.03) and controls ( p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls. [ABSTRACT FROM AUTHOR]

Currently the markers for the diagnosis of rheumatoid arthritis include inflammatory makers (including blood sedimentation and C-reactive protein), immune complexe and complement detection, detection of joint synovial fluid, and detection of autoantibodies. These indicators change with the activity of arthritis. Early diagnosis relies mainly on detection of autoantibodies. Anti-cyclic citrullinated peptide antibody (anti-CCP) is a kind of anti-keratin antibody, having higher sensitivity and specificity than the rheumatoid factor in diagnosis of rheumatoid arthritis. During the first year of rheumatoid arthritis, the existence of anti-CCP can be detected in the serum of most of these people. Positive anti-CCP can also be used to predict serious damage. Therefore, anti-CCP is extremely helpful in early diagnosis and prognosis assessment of rheumatoid arthritis. In this paper, the recent application of anti-CCP in the diagnosis of rheumatoid arthritis is reviewed. [ABSTRACT FROM AUTHOR]

Purpose: To determine the value of Anti-CCP as predictor for disease activity in rheumatoid arthritis assessed by DAS- 28, and to find the effect of smoking on disease activity in rheumatoid arthritis. Materials and Methods: One hundred patients with rheumatoid arthritis involved in this study, consisted of 88 female and 12 male who fulfilled the 2010 ACR-EULAR classification criteria for rheumatoid arthritis attending the rheumatology department in general hospital, or attended the center of rheumatology and rehabilitation in sulaimani city, for 6 months (from October, 2012 to March, 2013). Thorough Demographic information of patients was recorded through history of age, sex, and history of smoking, disease duration, physical evaluation according to DAS-28. and serological test for RF and Anti-CCP. Results: There was highly significant association between DAS-28 and Anti-CCP value (p =0.0001). there was no significant correlation between DAS-28 and RF (p= 0.252),According to smoking there was highly significant association between smoking with Anti-CCP value and DAS-28 (p=0.003- 0.0001) respectively while there was no significant association between smoking and RF(p=0.15). Conclusion: A highly significant correlation was found between Anti-CCP value and disease activity in rheumatoid arthritis, smoker patients had higher value of Anti-CCP compared to non-smoker patients. Smokers demonstrated a more active and severe disease activity compared to non-smokers. [ABSTRACT FROM AUTHOR]

ACPA (anti-citrullinated protein antibody) tests are today systematically added to clinical and radiological investigations when diagnosing rheumatoid arthritis (RA), and the inclusion of ACPA positivity in the new 2010 RA criteria underlines their importance. The aim of this study was to determine the sensitivity and specificity of different ACPA assays and IgA, IgG and IgM isotypes of rheumatoid factor (RF) in a cohort of patients with early RA in order to assess the value of combining the tests. The serum samples were obtained from 46 RA patients, 80 patients with systemic rheumatic disease, and 20 blood donors. ACPAs were measured using five different commercial kits. The receiver operating characteristic (ROC) curves of the anti-ACPA tests had area under the curve (AUC) values of 0.60-0.83. The diagnostic accuracy of the Bio-Rad multiplex flow immunoassay, a new technology for ACPA testing, was very similar to that of the other widely used commercial immunoassays. The EliA CCP-Phadia test was the most specific, and had the best positive likelihood ratio and positive predictive values, whereas the anti-CCP Inova 3.1 test was the most sensitive, and had the best negative likelihood ratio and negative predictive values. The best combination to use for early RA screening was an ACPA test together with IgM and IgA RF. [ABSTRACT FROM AUTHOR]

Background The gene encoding signal transducer and activator of transcription 4 (STAT4) has been reported to be associated with rheumatoid arthritis (RA) in several populations. This work aimed at assessing the association of STAT4 G>T gene polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. Subjects and methods This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for STAT4 G>T (rs7574865) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results Cases showed a significantly higher frequency of the STAT4 T allele carriage (GT+TT genotypes) compared to controls (51.8% vs. 31.1%, OR=2.37, 95% CI=1.39-4.05, p=0.001). Also the frequency of the STAT4 T allele was significantly higher among cases compared to controls (30.4% vs. 16.8%, OR=2.16, 95% CI=1.39-3.35, p=0.001). Cases positive to the STAT4 T allele (GT+TT genotypes) showed no significant difference compared to those with the GG genotype regarding their clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p=0.02). Conclusions This study gives an extra evidence to the association of the STAT4 T allele with the susceptibility and functional disability of RA. [ABSTRACT FROM AUTHOR]

Background Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results Elevated serum levels of anti-CII occurred in 3.1 %, IgM RF in 3.6 %, IgA RF in 3.1 % and anti-CCP in 2.6 % of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied. [ABSTRACT FROM AUTHOR]