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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]

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]

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]

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]

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease that can cause prolonged, inflamed, and progressive disability. MicroRNAs influence the processes of autoimmune disease through systemic consequences, including irritant activities of the immune system. Aim of the study: This research aims to evaluate the range of expression profile of the circulating miRNA155 gene as a potential diagnostic biomarker in RA patients in which specific antibodies with high sensitivity for RA are the anti-CCP antibodies. Method: The overall number comprised 36 RA patients and 14 healthy individuals with ages ranging from 20 to 60 years. All samples from patients and control are suspected of being diagnosed with the anticitrullinated protein antibodies test (ACPA) by the enzyme sorbent enzyme assay (ELISA). Relative quantification (RQ) of miRNA155 expression was performed after extraction of miRNA from serum from all participants and was estimated using RT- qPCR. Result: RA showed a significant increase in miRNA155 profile expression depending on the expression fold (11.12-fold expression ± 1.08), in comparison to healthy individuals, as significant (p ≤ 0.0001) of anti-ccp Abs in RA patients in whom they were at risk and evaluated the change in expression levels. In conclusion: The study identified upregulation in circulated miRNA155, which may serve as a prognostic form as a biomarker for the development of disease. [ABSTRACT FROM AUTHOR]

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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.

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]

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]

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.

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.)

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., Competing Interests: Declaration of competing interest Linda Mathsson-Alm is employed by Thermo Fisher Scientific. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). The CD4+CD25 high FoxP3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCs3) proteins. SOCs is produced at lower levels in RA. Our aim was to evaluate the expressional dysregulation of SOCs3 and FoxP3 genes in RA patients in relation to disease activity., Methods: We have recruited 90 patients with RA and 60 healthy controls in case control study. Whole blood samples were collected from RA patients and healthy subjects. The measurement of FoxP3 and SOCs3 gene expression was performed by real-time PCR (qPCR)., Results: Patients with RA had significantly decreased expression levels of FoxP3 and SOCs3 genes in comparison with controls (P<0.001), in addition to the insignificance correlation of both genes with disease activity in RA patients., Conclusion: FoxP3 and SOCs3 genes showed significant defects in rheumatoid arthritis patients with no significant difference in disease activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.