Search

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 aim of the study was to investigate the relationship between cytokine levels and values of antibodies to cyclic citrullinated peptide (anti-CCP) and antibodies to carbamylated proteins (anti-CarP) in patients with rheumatoid arthritis (RA). Materials and methods. 106 patients with a reliable diagnosis of rheumatoid arthritis were included in the study. Determination of anti-CarP and anti-CCP was performed by enzyme immunoassay. Patients were divided into subgroups depending on the values of anti-CCP and anti-CarP. The concentration of 27 cytokines in serum was determined using multiplex xMAR technology. Results and discussion. When comparing immunological subgroups, anti-CCP(+) patients had higher concentrations of interleukin (IL) 1β, IL-1Ra, IL-2, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, fibroblast growth factor, granulocyte colony-stimulating factor (CSF), granulocyte-macrophage CSF, interferon (IFN) γ, IFN0γ-induced protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α (MIP-1α), transforming growth factor bb, tumor necrosis factor α and vascular endothelial growth factor. IL-5, IL-9, eotaxin, MIP-1β and RANTES (regulated on activation, normal T cell expressed and secreted) values were higher in anti-CCP(–) patients. In the subgroup of anti-CCP(–) patients, an inverse correlation was found between IL-5 and total Sharpe score, between IL-9 and DAS28-CRP (Disease Activity Score with C-reactive protein calculation). In anti-Carp(–) patients (n=73) higher values of IL-17 were recorded. Conclusion. Our data support the concept of RA heterogeneity, characterised by the existence of different clinical and immunological subtypes, which may have implications for improving personalised therapy.

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]

Owing to limited usefulness of Rheumatoid Factor and anti-CCP in rheumatoid arthritis, there is a need to identify a more sensitive and specific biomarker to detect rheumatoid arthritis (RA), particularly seronegative RA cases. Tenascin-C is an extracellular matrix glycoprotein, which has been implicated in the pathophysiology of RA. The objective of our study was to evaluate the diagnostic utility of serum Tenascin-C in seropositive and seronegative rheumatoid arthritis patients. We conducted a cross-sectional case control study. Sixty patients who fulfilled the ACR 2010 criteria for rheumatoid arthritis were included in the study. Thirty patients were found to be positive for RF and/or anti-CCP and 30 were negative for both RF and anti-CCP. Thirty age and gender-matched healthy subjects were taken as controls. Serum Tenascin-C was measured by quantitative sandwich enzyme immunoassay technique. The mean serum concentration of Tenascin-C in controls, seronegative and seropositive cases was 0.66 ng/ml, 20.54 ng/ml and 23.42 ng/ml, respectively. Tenascin-C levels were significantly higher in RA cases compared to controls (p < 0.0001). There was no significant difference in Tenascin-C between seropositive and seronegative cases (p = 0.603). ROC curve analysis showed a sensitivity of 96.6% and specificity of 100% with AUC of 0.98 at 2.21 ng/ml as cut-off value for diagnosing RA. Tenascin-C is elevated in both seronegative and seropositive RA, which indicates that it can be used as a sensitive marker for RA. The addition of Tenascin-C to the existing RF and anti-CCP may help in identifying a large number of patients with RA, particularly seronegative rheumatoid arthritis cases. [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]

Abstract 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

Abstract 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

The aim of this study was to determine the Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotype frequency in Rheumatoid Arthritis (RA) in the Sudanese population. The frequency of HLA-DRB1 and -DQB1 alleles and DRB1-DQB1 haplotypes were determined in 122 RA patients and 100 controls. HLA alleles were genotyped by the polymerase chain reaction-sequence specific primers (PCR-SSP) method. In RA patients, HLA-DRB1*04 and *10 alleles were high in frequency (9.6% vs 14.2%, P = 0.038 and P = 0.042, respectively), and dependently on anti-citrullinated protein antibodies (ACPAs) seropositivity (P = 0.044 and P = 0.027, respectively). In contrast, the frequency of the HLADRB1* 07 allele was significantly low in patients than in controls (11.7% vs 5.0%, P = 0.010). Moreover, the HLA-DQB1*03 allele was strongly associated with RA risk (42.2%, P = 2.2x10-8), whereas, HLA-DQB1*02 and *06 showed protective effects against RA (23.1% and 42.2%, P = 0.024 and P = 2.2x10-6, respectively). Five different HLA haplotypes, DRB1*03-DQB1*03 (P = 0.00003), DRB1*04-DQB1*03 (P = 0.00014), DRB1*08-DQB1*03 (P = 0.027), DRB1*13-DQB1*02 (P = 0.004), and DRB1*13-DQB1*03 (P = 3.79x10-8) were significantly associated with RA risk, while 3 protective haplotypes, DRB1*03-DQB1*02 (Pc = 0.008), DRB1*07-DQB1*02 (Pc = 0.004), and DRB1*13-DQB1*06 (Pc = 0.02) were identified. This is the first study determining the association between HLA class II alleles and haplotypes and RA risk in our population. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Various proinflammatory cytokines are involved in the pathogenesis of this chronic disorder. It is characterized by the presence of autoantibodies, such as rheumatoid factor and antibodies against citrullinated peptides. The present study focuses on investigation of possible association between the proinflammatory cytokine interleukin 17 and anti-CCP, anti-MCV, and anti-CarP antibodies seropositivity in RA patients.Aim: To assess serum levels of interleukin 17 (IL-17) in patients with rheumatoid arthritis and healthy controls (HC) and to investigate the relationship between IL-17 and anti-cyclic citrullinated protein (anti-CCP) antibodies, antimutated citrullinated vimentin (anti-MCV) antibodies, and anti-carbamylated protein (anti-CarP) antibodies in patients with RA.Materials and methods: Forty-seven patients diagnosed with rheumatoid arthritis and 44 healthy controls were included in the study. Serum IL-17 levels were examined in all participants. Anti-CCP, anti-MCV, and anti-CarP antibodies were tested in the group of RA patients.Results: The mean serum level of IL-17 in RA patients was higher (12.8 pg/ml) than that in healthy controls (7.9 pg/ml), but the difference was not statistically significant (p=0.276). No significant correlation was observed between anti-CCP (+/−) and IL-17 (rs=0.162, p=0.380), and between anti-MCV (+/−) and IL-17 (rs=0.157, p=0.340). A significant positive correlation of moderate value was reported between anti-CarP (+/−) and IL-17 (rs=0.388, p=0.015). Conclusions: The present study demonstrated that the IL-17 serum levels in RA patients were increased compared to healthy controls. No correlation was found between ACPA immunological markers and IL-17 levels in patients with RA. A positive correlation was found between anti-CarP antibodies and IL-17 in the patients’ group. The increased level of IL-17 is suggestive of its possible role in the pathogenesis of CarP positive RA patients.

Background: Rheumatoid arthritis (RA) is an autoimmune disorder involving the synovial joints of humans. Recent research has demonstrated that vitamin D (VD3) can influence a person’s susceptibility to RA, and a proinflammatory mediator affects the pathogenesis of RA. Objectives: This work aimed to investigate the correlation of VD3 with autoantibodies and interleukin-12 (IL-12) in RA patients. Materials and Methods: Eighty women were included in this case–control study, 60 confirmed RA and 20 healthy controls (HC) of the age range 29–71 years. The sera of study subjects were examined for anticyclic citrullinated peptides (anti-CCP), vitamin D3, and IL-12 by enzyme-linked immunosorbent assay. Rheumatoid factor (RF-IgG) was tested by latex agglutination technique. Results: The present findings revealed a significantly high concentration of anti-CCP, RF-IgG, and IL-12 in RA patients in comparison to HC. The anti-CCP expressed high sensitivity and specificity at 80% and 100% compared to RF-IgG at 76.6% and 90%, respectively. Both RA patients and HC groups showed lower levels of VD3 with a nonsignificant difference, 50% of RA patients and 55% of the HC had vitamin D deficiency (

The aim of this study was to determine the Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotype frequency in Rheumatoid Arthritis (RA) in the Sudanese population. The frequency of HLA-DRB1 and -DQB1 alleles and DRB1-DQB1 haplotypes were determined in 122 RA patients and 100 controls. HLA alleles were genotyped by the polymerase chain reaction-sequence specific primers (PCR-SSP) method. In RA patients, HLA-DRB1*04 and *10 alleles were high in frequency (9.6% vs 14.2%, P = 0.038 and P = 0.042, respectively), and dependently on anti-citrullinated protein antibodies (ACPAs) seropositivity (P = 0.044 and P = 0.027, respectively). In contrast, the frequency of the HLA-DRB1*07 allele was significantly low in patients than in controls (11.7% vs 5.0%, P = 0.010). Moreover, the HLA-DQB1*03 allele was strongly associated with RA risk (42.2%, P = 2.2x10-8), whereas, HLA-DQB1*02 and *06 showed protective effects against RA (23.1% and 42.2%, P = 0.024 and P = 2.2x10-6, respectively). Five different HLA haplotypes, DRB1*03-DQB1*03 (P = 0.00003), DRB1*04-DQB1*03 (P = 0.00014), DRB1*08-DQB1*03 (P = 0.027), DRB1*13-DQB1*02 (P = 0.004), and DRB1*13-DQB1*03 (P = 3.79x10-8) were significantly associated with RA risk, while 3 protective haplotypes, DRB1*03-DQB1*02 (Pc = 0.008), DRB1*07-DQB1*02 (Pc = 0.004), and DRB1*13-DQB1*06 (Pc = 0.02) were identified. This is the first study determining the association between HLA class II alleles and haplotypes and RA risk in our population.

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]

Copyright of Al-Mustansiriyah Journal of Science is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Musculoskeletal (MSK) symptoms are among the commonest reasons for primary care assessments; however, few individuals will be diagnosed with an inflammatory arthritis (IA) within the following year. The purpose of this study was to investigate, in individuals with new MSK symptoms, the association between patient factors and risk of progression to IA, in order to optimise primary care referrals to rheumatology. Methods Individuals ≥16 years old with new non-specific MSK symptoms and no clinical synovitis were recruited by primary care across the UK from July 2007 until May 2019. Those testing positive for the anti-CCP2 assay (anti-CCP+) were invited to Leeds for follow-up. Subjects with a negative result (anti-CCP−) were sent a 1-year questionnaire, and general practitioners were contacted to confirm whether the individual had been diagnosed with an IA by a rheumatologist. Predictors for progression were assessed using multivariable regression analysis. Results Six thousand seven hundred eighty individuals were recruited: 3% were anti-CCP+, of whom 45% progressed to IA, predominantly rheumatoid arthritis. Anti-CCP+ participants with high antibody levels had an odds ratio (OR) for progression to IA of 9.42 [P < 0.001, 95% CI (3.13–28.30)], hand pain, OR 2.74 [P = 0.043, 95% CI (1.03–7.27)] and foot pain, OR 4.10 [P = 0.003, 95% CI (1.59–10.54)]. In low-level anti-CCP+ individuals, absence of pain in hands or feet had a negative predictive value of 96% for progression to IA. One-year follow-up data were available for 5640 anti-CCP− individuals, of whom 53 were diagnosed with IA (0.93%). Pain in hands, OR 2.51 [P = 0.018, 95% CI (1.17–5.39)] or knees, OR 3.03 [P = 0.003, 95% CI (1.47–6.25)] were associated with development of IA within 12 months. Conclusions This is the largest prospective primary care study of individuals at risk of IA, and the first one to prospectively investigate the outcome of MSK symptoms in a large anti-CCP− cohort. High anti-CCP levels and pain in hands/feet indicated an increased likelihood of progression to IA. In patients with low anti-CCP level and no pain in the hands/feet, progression is unlikely. In anti-CCP− patients, those with hand or knee pain were at increased risk of progression. This study demonstrates that routinely available tests and joint symptoms provide useful discrimination that may be used to prioritise referrals to rheumatology and avoid a delayed diagnosis. Trial registration NCT, NCT02012764 . Registered 25 January 2007.

Vitamin D considered as a key player in various autoimmune disorders, such as rheumatoid arthritis, due to its immunological modulatory effect. Together with Anti-double stranded DNA (Anti-dsDNA), Anti-cyclic citrullinated peptide (Anti-CCP) is considered among the indicators of the disease severity in rheumatoid arthritis. The present study aimed to measure the level of vitamin D in RA patients besides measuring anti-dsDNA, anti-CCP, RF, complete blood count (CBC) and Erythrocyte Sedimentation Rate (ESR) for comparing it with its corresponding level in healthy control group. This study was a descriptive cross-sectional study involving sequential RA patients who visited the Rheumatology clinic for outpatients during three-months period starting from July 2018, at the Baghdad Teaching Hospital. Sixty individuals (30 RA patients and 30 age and gender matched healthy control) were enrolled in this study. Blood samples were collected and serum levels of anti-dsDNA, 25-hydroxy vitamin D (25[OH]), anti-CCP and RF besides C3, C4, CBC and ESR were measured. A highly significant decrease was displayed in the mean level of vitamin D in RA patients (18.67±17.70 ng/mL) when compared to its level in the control group (35.07 ±3.71 ng/mL), (normal value: 20 and 40 ng/mL), whereas, anti-dsDNA level normal value: (

Abstract Background Rheumatoid arthritis (RA), an autoimmune disorder, characterized by systemic inflammation and swollen joints, establishes itself as a critical threat. A pro-inflammatory cytokine TNF-α is a well-known driver of RA pathogenesis and at the same time predisposes to insulin resistance through signal impediment which ultimately paves the way for type 2 diabetes (T2DM). However, in patients with RA, T2DM remains significantly undiagnosed or undertreated, apparently which increases the risk of developing cardio-metabolic comorbidities. This study aimed to evaluate the glycemic status among RA patients and its association with disease activity. Result One hundred fifty inpatients RA cases according to ACR/EULAR standards were included in the cross-sectional study who have an average age of 45.4±12.15 years and a median and interquartile period of RA of 2.25 years and 0.48–6 years, respectively. We discovered that 36% of people had T2DM, 26% were prediabetic, and 38% were non-diabetic. Age was shown to be significantly correlated with DM frequency in RA patients (p=0.007). There were 28 patients with elevated disease activity (19%) and 60 patients with low disease activity (40%) in this study. No substantial associations were found in the presence of DM with gender, anti-CCP, RF, disease duration, or DAS28. Conclusion RA patients are more likely to experience diabetes, and resultantly a high index of notion must be kept. Clinician should be aware about the affliction of undiagnosed diabetes and prediabetes in RA patients. Furthermore, keeping an eye on glycemic control in RA patients could prevent metabolic and cardiovascular comorbidities in those susceptible patients.

Abstract Background There is a need for biomarker to identify patients “at risk” for rheumatoid arthritis (risk-RA) and to better predict the therapeutic response and in this study we tested the hypothesis that novel native and citrullinated heterogeneous nuclear ribonucleoprotein (hnRNP)-DL autoantibodies could be possible biomarkers. Methods Using protein macroarray and ELISA, epitope recognition against hnRNP-DL was analysed in sera from different developed RA disease and diagnosed SLE patients. Toll-like receptor (TLR) 7/9 and myeloid differentiation primary response gene 88 (MyD88)-dependency were studied in sera from murine disease models. HnRNP-DL expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry. Results HnRNP-DL was highly expressed in stress granules, citrullinated in the rheumatoid joint and targeted by autoantibodies either as native or citrullinated proteins in patient subsets with different developed RA disease. Structural citrullination dependent epitopes (SCEs) of hnRNP-DL were detected in 58% of the SLE patients although 98% of these sera were α-CCP-2-negative. To obtain a specific citrullinated signal value, we subtracted the native antibody value from the citrullinated signal. The citrullinated/native index of autoantibodies against hnRNP-DL (CNDL-Index) was identified as a new value for an “individual window of treatment success” in early RA and for the detection of RF IgM/α-CCP-2 seronegative RA patients (24–46%). Negative CNDL-index was found in SLE patients, risk-RA and early RA cohorts such as EIRA where the majority of these patients are DAS28-responders to methotrexate (MTX) treatment (87%). High positive CNDL-values were associated with more severe RA, shared epitope and parenchymal changes in the lung. Specifically, native α-hnRNP-DL is TLR7/9-dependent, associated with pain and ROC analysis revealed an association to initial MTX or etanercept treatment response, especially in seronegative RA patients. Conclusion CNDL-index defines people at risk to develop RA and the “window of treatment success” thereby closing the sensitivity gap in RA.

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]

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.

anti-CCP, anticyclic citrullinated peptide antibodies, chemiluminescence immunoassay (CLIA), diagnosis, electrochemiluminescence immunoassay (ECLIA), enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric assay (ITA), rheumatoid arthritis [ABSTRACT FROM AUTHOR]

Background: Rheumatoid Arthritis (RA) is a progressive, chronic type of autoimmune disease and the role of vitamin D in the pathogenesis of RA is under investigation. Objective: The objective of this study was to determine the vitamin D deficiency in patients with RA as compared to healthy controls and to assess the relationship between serum vitamin D and anti-cyclic citrullinated peptide (anti-CCP) antibody levels in patients with newly diagnosed rheumatoid arthritis. Methods: The study was conducted between January 2017 to February 2018 at Fishtail Hospital and Research centre. A total of 63 patients with early RA diagnosed and a control group of 56 healthy participants, not on vitamin D supplements were recruited from Department of Internal Medicine. Five ml of blood samples were drawn from cubital veins. Blood glucose, creatinine, uric acid, calcium, RA factor, 25-hydroxy vitamin D, anti-CCP antibody, and erythrocyte sedimentation rates were measured in a centralized laboratory of Fishtail Hospital and Research centre. Results: The level of serum 25-hydroxy vitamin D were significantly lower in RA group (20.03 ±9.97 ng/mL) in comparison to the control group (24.46 ±8.45 ng/mL) (p

Measurement of two groups of autoantibodies, rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) have gained increasing significance in the diagnosis and classification of rheumatoid arthritis (RA) over the last 65 years. Despite this rising importance of autoimmune serology in RA, there is a palpable lack of harmonization between different commercial RF and ACPA tests. While a minimal diagnostic specificity has been defined for RF tests, which almost always are related to an international reference preparation, neither of this applies to ACPA. Especially assays with low diagnostic specificity are associated with very low positive predictive values or post-test probabilities in real world settings. In this review we focus on issues of practical bearing for the clinical physician diagnosing patients who potentially have RA, or treating patients diagnosed with RA. We advocate that all clinically used assays for RF and ACPA should be aligned to a common diagnostic specificity of 98-99% compared to healthy controls. This high and rather narrow interval corresponds to the diagnostic specificity seen for many commercial ACPA tests, and represents a specificity that is higher than what is customary for most RF assays. Data on antibody occurrence harmonized in this way should be accompanied by test result-specific likelihood ratios for the target diagnosis RA on an ordinal or interval scale, which will provide the clinical physician with more granular and richer information than merely relating numerical values to a single cut-off point. As many physicians today are used to evaluate autoantibodies as positive or negative on a nominal scale, the introduction of test result-specific likelihood ratios will require a change in clinical mindset. We also discuss the use of autoantibodies to prognosticate future arthritis development in at-risk patients as well as predict severe disease course and outcome of pharmacological treatment.

Measurement of two groups of autoantibodies, rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) have gained increasing significance in the diagnosis and classification of rheumatoid arthritis (RA) over the last 65 years. Despite this rising importance of autoimmune serology in RA, there is a palpable lack of harmonization between different commercial RF and ACPA tests. While a minimal diagnostic specificity has been defined for RF tests, which almost always are related to an international reference preparation, neither of this applies to ACPA. Especially assays with low diagnostic specificity are associated with very low positive predictive values or post-test probabilities in real world settings. In this review we focus on issues of practical bearing for the clinical physician diagnosing patients who potentially have RA, or treating patients diagnosed with RA. We advocate that all clinically used assays for RF and ACPA should be aligned to a common diagnostic specificity of 98-99% compared to healthy controls. This high and rather narrow interval corresponds to the diagnostic specificity seen for many commercial ACPA tests, and represents a specificity that is higher than what is customary for most RF assays. Data on antibody occurrence harmonized in this way should be accompanied by test result-specific likelihood ratios for the target diagnosis RA on an ordinal or interval scale, which will provide the clinical physician with more granular and richer information than merely relating numerical values to a single cut-off point. As many physicians today are used to evaluate autoantibodies as positive or negative on a nominal scale, the introduction of test result-specific likelihood ratios will require a change in clinical mindset. We also discuss the use of autoantibodies to prognosticate future arthritis development in at-risk patients as well as predict severe disease course and outcome of pharmacological treatment. [ABSTRACT FROM AUTHOR]

La Artritis Reumatoide (ar) es una enfermedad autoinmune inflamatoria sistémica crónica, que cursa con inflamación persistente de la membrana sinovial articular. Con el tiempo, pueden aparecer: erosión ósea, destrucción del cartílago articular y la pérdida completa de la integridad de la articulación. Por último, pueden afectarse diversos órganos y sistemas.La inflamación de las articulaciones de los pies, manos, rodillas y en general cualquier ar-ticulación (poliarticular), son de característica simétrica y elevado deterioro funcional. La arse caracteriza por la presencia de autoanticuerpos, como el factor reumatoide (fr) y los anticuerpos antipéptidos cíclicos citrulinados (anti-ccp). Sin tratamiento, dentro de los 3 años de realizado el diagnóstico, el 20 al 30% de las per-sonas con ar llegan a la discapacidad permanente. Pacientes con sinovitis de más de 6 semanas son más propicios a desarrollar una enfermedad progresiva y no un proceso au-tolimitado. Las nuevas terapias biológicas han transformado radicalmente la evolución de la enfermedad, permitiendo a los pacientes mantener su independencia funcional y mejorando su calidad de vida

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affect 1-2% of people worldwide. Inflammation is an important factor in the pathogenesis of RA. Anti- Cyclic Citrullinated Peptid (Anti-CCP) antibody and Rheumatoid Factor (RF) are autoantibodies that promotes inflammatory reactions and have a crucial role in RA pathogenesis. Treg cells are necessary for the maintenance of immune homeostasis and prevention of autoimmunity. FoxP3 is essential transcription factor for development of these regulatory cells. In this study, we surveyed the effects of FoxP3 gene expression in peripheral blood on plasma levels of Anti-CCP and RF. Methods: Peripheral blood samples were collected from 47 patients and 44 healthy subjects. Then plasma levels of Anti-CCP have been evaluated using ELISA method. Also RF was detected with latex agglutination test, and gene expression of FoxP3 analyzed by real time PCR . Results: The amount of Anti-CCP and RF were significantly higher in our patients in comparison with healthy subjects (P

Abstract Background Infection by common viruses has long been discussed in the aetiology of a number of autoimmune diseases, including rheumatoid arthritis (RA). However, studies investigating this hypothesis in RA show conflicting results. These studies often lack well-matched control populations, and many do not include data on autoantibodies, genetic risk factors and other environmental factors, which are known to contribute to disease only in subgroups of patients. In the present study, we have therefore examined the role of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B19 (B19) in RA aetiology, by analysing anti-viral antibodies in relation to anti-citrullinated protein antibodies (ACPA), smoking, HLA-DRB1 shared epitope (SE) alleles, and clinical parameters, in both RA patients and matched controls. Methods Anti-viral antibodies were measured by ELISA in serum samples from 990 RA patients and 700 controls from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort. Data on ACPA, smoking, SE, inflammation (C-reactive protein) and disease activity score in 28 joints (DAS28) was obtained from the EIRA database. Fisher’s exact test, the chi-squared test, and the Mann-Whitney U test were used to calculate differences in anti-viral antibody frequencies and levels; unconditional logistic regression was used to determine the association of anti-viral antibodies with different RA subsets. Results Antibodies against all viruses were highly prevalent in EIRA, with no major differences detected between ACPA-positive RA, ACPA-negative RA and controls. However, both anti-B19 and anti-EBV IgG levels were significantly lower in ACPA-positive RA compared to controls, and there were significant interactions between low levels of anti-B19 and anti-EBV antibodies and SE in the development of ACPA-positive RA. Conclusion We could not detect an association between RA and elevated anti-viral antibody levels, for any of the three common viruses, EBV, CMV or B19. On the contrary, our study demonstrated association between low anti-EBV/anti-B19 antibody levels and ACPA-positive RA, in particular when HLA-DRB1 SE was present. These data could potentially suggest that high anti-viral antibody levels would be protective against ACPA-positive RA. Further investigations are required to address the mechanisms behind these findings.

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 anti-cyclic citrullinated peptide (anti-CCP) (p

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

Rheumatoid meningitis is a rare extra-articular manifestation of rheumatoid arthritis, often with non-specific symptoms. In most cases brain MRI shows a patchy lepto- and pachymeningeal enhancement, but the diagnosis currently relies on examination of a meningeal biopsy with presence of plasma cells and rheumatoid noduli. Presence of IgM rheumatic factor (RF) has been found in several cases and recently four cases have shown high titer anti-cyclic citrullinated peptide (anti-CCP) in CSF, suggesting this as a potential marker for rheumatoid meningitis. We present a 62 year-old woman with sero-positive (IgM RF and anti-CCP) rheumatoid arthritis, presenting with headache and gait impairment. Brain MRI revealed the classical patchy meningeal enhancement and the diagnosis of rheumatoid meningitis was confirmed by neuropathological examination of a meningeal biopsy. Analysis of the CSF revealed positive IgM RF (92.7 IU/mL) and strongly positive anti-CCP (19,600 IU/mL) and CXCL-13 (>500 ng/L). After treatment with high-dose steroid and Rituximab the clinical symptoms resolved. A 6 month follow-up analysis of CSF showed a dramatic decrease in all these markers with negative IgM RF and a decrease in both anti-CCP (64 IU/mL) and CXCL-13 (

Rheumatoid arthritis (RA) associated anti-citrullinated protein autoantibodies (ACPA) target a wide range of modified proteins. Citrullination occurs during physiological processes such as apoptosis, yet little is known about the interaction of ACPA with nuclear antigens or apoptotic cells. Since uncleared apoptotic cells and neutrophil extracellular trap (NET) products have been postulated to be central sources of autoantigen and immunostimulation in autoimmune disease, we sought to characterize the anti-nuclear and anti-neutrophil reactivities of ACPA. Serology showed that a subset of anti-CCP2 seropositive RA patients had high reactivity to full-length citrullinated histones. In contrast, seronegative RA patients displayed elevated IgG reactivity to native histone compared to controls, but no citrulline-specific reactivity. Screening of 10 single B-cell derived monoclonal ACPA from RA patients revealed that four ACPA exhibited strong binding to apoptotic cells and three of these had anti-nuclear (ANA) autoantibody reactivity. Modified histones were confirmed to be the primary targets of this anti-nuclear ACPA subset following immunoprecipitation from apoptotic cell lysates. Monoclonal ACPA were also screened for reactivities against stimulated murine and human neutrophils, and all the nuclear-reactive monoclonal ACPA bound to NETs. Intriguingly, one ACPA mAb displayed a contrasting cytoplasmic perinuclear neutrophil binding and may represent a different NET-reactive ACPA subset. Notably, studies of CRISPR-Cas9 PAD4 KO cells and cells from PAD KO mice showed that the cytoplasmic NET-binding was fully dependent on PAD4, whilst nuclear- and histone-mediated NET reactivity was largely PAD-independent. Our further analysis revealed that the nuclear binding could be explained by consensus-motif driven ACPA cross-reactivity to acetylated histones. Specific acetylated histone peptides targeted by the monoclonal antibodies were identified and the anti-modified protein autoantibody (AMPA) profile of the ACPA was found to correlate with the functional activity of the antibodies. In conclusion, when investigating monoclonal ACPA, we could group ACPA into distinct subsets based on their nuclear binding-patterns and acetylation-mediated binding to apoptotic cells, neutrophils, and NETs. Differential anti-modified protein reactivities of RA-autoantibody subsets could have an important functional impact and provide insights in RA pathogenesis.

Silymarin is known for its anti-inflammatory and antioxidant properties. We investigated these effects on serum levels of CTRP3, Anti-CCP, and hs-CRP in individuals with Rheumatoid arthritis (RA). In this study, 42 individuals with RA were recruited and their serum specimens were collected, serum levels of hs-CRP, AntiCCP antibodies, and CTRP3 were measured using ELISA. DNA was extracted and investigated for the existence of possible new mutations in the gene encoding CTRP3 using the PCR technique; the desired fragments were then amplified and sequenced. Another blood sample was collected from the case group after taking livergol for three months (3 doses of 140 mg/day) and the tests were repeated. Anti-CCP Abs levels in the postintervention responding group decreased compared to preintervention (p<0.001) while in the non-responding group, the levels increased after the intervention compared to the levels before the intervention (p=0.019). Additionally, CTRP3 levels in the responding group increased postintervention (p=0.003), however, in the non-responding group the levels decreased postintervention when compared to preintervention (p=0.02). The responding group had significantly lower levels of hs-CRP when compared to that of preintervention (p=0.005) whereas the non-responding group had significantly higher levels of postintervention (p<0.001). Moreover, the results of sequencings of exon 6 on CTRP3 gene showed the presence of mutations in exon 6 (position 215:C>T, 338:G>A, 359:A>C, and 153:T>C). Silymarin could be used as an adjuvant in the treatment of rheumatoid arthritis., Competing Interests: The authors declare that they have no conflict of interest.

Rheumatoid meningitis is a rare extra-articular manifestation of rheumatoid arthritis, often with non-specific symptoms. In most cases brain MRI shows a patchy lepto- and pachymeningeal enhancement, but the diagnosis currently relies on examination of a meningeal biopsy with presence of plasma cells and rheumatoid noduli. Presence of IgM rheumatic factor (RF) has been found in several cases and recently four cases have shown high titer anti-cyclic citrullinated peptide (anti-CCP) in CSF, suggesting this as a potential marker for rheumatoid meningitis. We present a 62 year-old woman with sero-positive (IgM RF and anti-CCP) rheumatoid arthritis, presenting with headache and gait impairment. Brain MRI revealed the classical patchy meningeal enhancement and the diagnosis of rheumatoid meningitis was confirmed by neuropathological examination of a meningeal biopsy. Analysis of the CSF revealed positive IgM RF (92.7 IU/mL) and strongly positive anti-CCP (19,600 IU/mL) and CXCL-13 (>500 ng/L). After treatment with high-dose steroid and Rituximab the clinical symptoms resolved. A 6 month follow-up analysis of CSF showed a dramatic decrease in all these markers with negative IgM RF and a decrease in both anti-CCP (64 IU/mL) and CXCL-13 (<10 ng/L). Our case further underlines the potential use of CSF anti-CCP and IgM RF in the diagnosis of RM and the use of these markers and CXCL-13 in evaluation of treatment response. A case review of 48 cases of rheumatoid meningitis published since 2010, including, symptoms, serum, and CSF findings, treatment, and outcome is provided. [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]

Background: Patients with rheumatoid arthritis (RA) have increased coronary atherosclerosis possibly related to several factors including insulin resistance. Anti-CCP antibodies are highly specific for RA but their association with cardiovascular morbidity has not been examined by enough studies. Aim: The aim of this study was to evaluate the role of anti ccp antibodies and IR for detection of early and sub-clinical atherosclerosis in RA patients. Subjects and methods: 56 RA patients and 19 age and sex matched healthy subjects were included in the present study. All patients and controls were subjected to full history, clinical examination, and laboratory investigations (including CBC, ESR, high sensitive CRP, rheumatoid factor and lipid profile). All patients were also subjected to measurement of intima-media thickness (IMT) of both carotid arteries as well as the flow mediated dilatation (FMD) of brachial artery. Also, measurements of IR (by HOMA 2) and anti-CCP were done for all subjects. Results: IMT was significantly increased (P = 0.01) and FMD significantly decreased (P = 0.001) in RA patients than controls in spite of the absence of significant differences in traditional atherosclerotic risk factors. Both IR and anti-CCP (which are significantly increased in RA compared to controls, P = 0.02 and 0.001 respectively) were significantly positively correlated to IMT (P = 0.009 and 0.001 respectively) and negatively correlated to FMD (P = 0.0005 and 0.005 respectively). Conclusion: IR and anti-CCP may be helpful in the early detection of subclinical atherosclerosis in RA patients.

Background:Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis (RA) pathogenesis. Although mechanistic and clinical association studies implicate Aa infection in the initiation of autoimmunity in RA, direct evidence in humans is lacking.Case:We describe a 59-year-old man with anti-citrullinated protein antibody (ACPA)-positive RA who presented for evaluation of refractory disease. He was found to have Aa endocarditis. Following antibiotic treatment, joint symptoms resolved and ACPAs normalized. Given the implications for RA immunopathogenesis, we further investigated the bacterial, genetic and immune factors that may have contributed to the patient's clinical and autoimmune phenotypes.Methods:DNA was extracted from serum and used to amplify the Aa leukotoxin (ltx) promoter region by PCR, which was further analyzed by Sanger sequencing. High-resolution identification of HLA alleles was performed by sequenced based typing (SBT). TNF-α, IFN-γ, GM-CSF, IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-21, and IL-22 were quantified in serum by a multiplex immunoassay. IgG and IgA antibodies to Aa LtxA were assayed by ELISA.Results:Aa genotyping confirmed infection with a highly leukotoxic strain carrying a 530-bp ltx promoter deletion, shown to result in 10- to 20-fold higher bacterial expression of LtxA. Immuno-phenotyping showed high anti-LtxA antibodies, elevated cytokines implicated in RA pathogenesis (Th1/Th17), and specific host susceptibility conferred by three HLA alleles strongly linked to ACPAs and RA (DRB1*04:04, DRB1*15:01, and DPB1*04:01). One year after eradication of Aa, the patient remained free of arthritis and anti-CCP antibodies.Conclusion: In the context of genetic risk for RA, systemic subacute infection with a leukotoxic strain of Aa can drive ACPA production and a clinical phenotype similar to RA.

Background: Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis (RA) pathogenesis. Although mechanistic and clinical association studies implicate Aa infection in the initiation of autoimmunity in RA, direct evidence in humans is lacking. Case: We describe a 59-year-old man with anti-citrullinated protein antibody (ACPA)-positive RA who presented for evaluation of refractory disease. He was found to have Aa endocarditis. Following antibiotic treatment, joint symptoms resolved and ACPAs normalized. Given the implications for RA immunopathogenesis, we further investigated the bacterial, genetic and immune factors that may have contributed to the patient's clinical and autoimmune phenotypes. Methods: DNA was extracted from serum and used to amplify the Aa leukotoxin (ltx) promoter region by PCR, which was further analyzed by Sanger sequencing. High-resolution identification of HLA alleles was performed by sequenced based typing (SBT). TNF-α, IFN-γ, GM-CSF, IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-21, and IL-22 were quantified in serum by a multiplex immunoassay. IgG and IgA antibodies to Aa LtxA were assayed by ELISA. Results: Aa genotyping confirmed infection with a highly leukotoxic strain carrying a 530-bp ltx promoter deletion, shown to result in 10- to 20-fold higher bacterial expression of LtxA. Immuno-phenotyping showed high anti-LtxA antibodies, elevated cytokines implicated in RA pathogenesis (Th1/Th17), and specific host susceptibility conferred by three HLA alleles strongly linked to ACPAs and RA (DRB1*04:04, DRB1*15:01, and DPB1*04:01). One year after eradication of Aa , the patient remained free of arthritis and anti-CCP antibodies. Conclusion: In the context of genetic risk for RA, systemic subacute infection with a leukotoxic strain of Aa can drive ACPA production and a clinical phenotype similar to RA. [ABSTRACT FROM AUTHOR]

Background. Viruses are common and are involved in the etiology of idiopathic rheumatological diseases. Hepatitis B virus (HBV), a member of the family Hepadnaviridae and hepatitis C virus (HCV), play an important role in the undetermined etiology of arthritis. The clinical manifestations of hepatitis B and C show similarities with various diseases, such as rheumatic diseases. Anti-cyclic citrullinated peptide (anti-CCP) is a specific serological marker for rheumatoid arthritis. Objectives. The aim of this study was to analyze anti-CCP and rheumatoid factor (RF) levels in patients with a hepatitis B and C infection. Material and methods. Forty-four patients with hepatitis B, 43 patients with hepatitis C, 25 patients with rheumatoid arthritis, and 46 healthy control serums and their RF and anti-CCP levels were compared. RF was measured by the nephelometer, which detects IgM-RF. Anti-CCP was measured using enzymelinked immunosorbent assay (ELISA) that is included in the second-generation anti-CCP antibody assays (anti-CCP2). Results. The anti-CCP positivity levels were 20.5%, 32.5%, 72.4% and 10.9% for HBV, HCV and RA groups and healthy control group, respectively. When the groups were compared based on their RF positivity and anti-CCP positivity while the values for HBV and HCV group and healthy control group were the same, in RA group there is a significant difference to the rest of the groups (p < 0.01). Conclusions. Anti-CCP may be positive for HBV and HCV as well, but it is a sensitive and specific immunological marker for RA diagnosis, especially in high-titres. [ABSTRACT FROM AUTHOR]

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

Introduction:  Human leukocyte antigens (HLA) account for up to one-half of the total genetic contribution to rheumatoid arthritis (RA) risk. The study investigated the association of HLA class II genotyping with RA susceptibility in Sudanese ethnic groups., Methods:  The DRB1 and DQB1 alleles and haplotypes were determined in 122 RA patients (i.e., Gaalia = 54, Johayna = 24, Baggara = 17, Nile Nubian = 12, and others = 15) and 120 healthy controls of ethnic groups (i.e., Gaalia = 44, Johayna = 11, Baggara = 15, Nile Nubian = 9, and others = 21) using a polymerase chain reaction with sequence-specific primers method., Results: Susceptibility to RA was associated with a high frequency of DRB1*04 (P = 0.04), DRB1*10 (P = 0.04), and DQB1*03 (P = 2.2 x 10 -8 /P c = 6.6 x 10 -8 ) between study ethnic groups, while protective effects were shown with DRB1*07 (P = 0.01), DQB1*02 (P = 0.02), and DQB1*06 (P = 2.2 x 10 -6 /P c  = 6.6 x 10 -6 ), with an inconsistent frequency between study ethnic groups. The HLA haplotypes that were high in frequency among RA ethnic groups and showed susceptibility associations were DRB1*03-DQB1*03, DRB1*04-DQB1*03, DRB1*08-DQB1*03, DRB1*13-DQB1*02, and DRB1*13-DQB1*03 (P = 0.00003/P c = 0.0003, P = 0.0001/P c  = 0.0001, P = 0.03, P = 0.004/P c  = 0.03, and P = 3.79x10 -8 /P c  = 3.3x10 -9 , respectively). On the contrary, DRB1*03-DQB1*02, DRB1*07-DQB1*02, and DRB1*13-DQB1*06 were lower in frequency in the ethnic groups with RA and may confer protection (P = 0.004/P c  = 0.032, P = 0.002/P c  = 0.02, and P = 0.01, respectively)., Conclusions: Our findings indicate an association between HLA-DRB1 and DQB1 genotypes and the susceptibility to RA in the Sudanese population, with a moderate frequency between our ethnic groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ali et al.)