Anti-mutated Citrullinated Vimentin Antibodies Research Articles

Association of ERAP1 and ERAP2 gene polymorphisms and ERAP2 protein with the susceptibility and severity of rheumatoid arthritis in the Ukrainian population.

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. Although RA is chiefly associated with HLA class II, nevertheless some HLA class I associations have also been observed. These molecules present antigenic peptides to CD8+ T lymphocytes and natural killer cells. HLA-I molecules bind their peptide cargo (8-10 amino acids long) in the endoplasmic reticulum. Peptides longer than 10 amino acids are trimmed by the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 to fit the peptide binding groove of the HLA-I molecule. Here, we investigated the possible association of ERAP1 and ERAP2 polymorphisms with RA, and also any possible correlation between serum levels of the ERAP2 protein with disease severity. We used Real-Time PCR to genotype ERAP1 and ERAP2 and ELISA test to detect ERAP2 protein. We found significant associations of ERAP1 rs30187, rs27044, and rs26618, as well as ERAP2 rs2248374, with susceptibility to RA. ERAP1 rs26653 and ERAP2 rs2248374 were also associated with the Disease Activity Score (DAS28), and some polymorphisms were also associated with anti-citrullinated protein or anti-mutated citrullinated vimentin antibodies. RA patients secreted higher concentrations of ERAP2 than controls. Patients with mild disease activity (DAS28 < 3.2) released a concentration of ERAP2 four times lower than that of patients with severe disease activity (DAS28 > 5.1). We detected a higher level of ERAP2 in rheumatoid factor (RF)-positive patients than in RF-negative patients. ERAP2 concentration above 5.85 ng/mL indicated a severe phase of RA. Some ERAP1 and ERAP2 polymorphisms seem to be related to susceptibility to RA or the severity of the disease. The ERAP2 protein tested in serum could be a valuable biomarker of RA severity.

Anti-mutated citrullinated vimentin antibodies as a biomarker for interstitial lung disease in patients with rheumatoid arthritis.

We aimed to assess the anti-mutated citrullinated vimentin (anti-MCV) antibodies in RA patients' serum and to explore their association with interstitial lung disease (ILD). Eighty rheumatoid arthritis (RA) patients and forty healthy controls were included in this case-control study. Of these patients, forty had ILD, and forty without ILD. Patients were subjected to clinical and laboratory assessment, measurement of anti-MCV serum levels by ELISA, X-ray of hands and feet, pulmonary function tests, and high-resolution computed tomography (HRCT) of the chest. Increased serum level of anti-MCV antibodies was found in RA patients compared with the controls and in RA patients with ILD compared to those without ILD. The serum anti-MCV level was correlated positively with disease activity score 28 (DAS28), Larsen, erythrocyte sedimentation rate (ESR), and anti-citrullinated peptides antibodies (ACPA) and negatively with the diffusing capacity for carbon monoxide (DLCO), and forced vital capacity (FVC). Patients' age, disease duration, ACPA level, anti-MCV level, and anti-MCV positivity were predictors of ILD in our patients. At the 42.5 U/ml cut-off, the anti-MCV antibodies have 78.8% sensitivity and 80% specificity for RA, and at the 155.5 U/ml cut-off, their sensitivity is 80%, and their specificity is 75% for ILD. Anti-MCV antibodies are increased in RA patients with ILD with high sensitivity and specificity; thus, they may represent a promising marker for early detection and prediction of RA-related ILD. In addition, anti-MCV antibodies positively correlate with the Larsen score; hence, they may be a valuable serological marker for predicting joint damage in RA patients. More research with large sample sizes is recommended to support our findings.

Evaluation of the clinical performance of anti-mutated citrullinated vimentin antibody and 14-3-3 eta testing in rheumatoid arthritis.

Early rheumatoid arthritis (RA) detection is crucial for improving patient prognosis. Anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) support RA diagnosis but are undetectable in ∼20 % of cases. Recently, antibodies against mutated citrullinated vimentin (anti-MCV) and detection of 14-3-3 eta have emerged with implications for preclinical RA diagnosis and monitoring treatment. The objective of this study was to assess the clinical performance of anti-MCV antibodies and 14-3-3 eta in RA and to compare it to current RA criteria anti-CCP and RF markers, individually and in combination. A retrospective chart review of 326 subjects submitted for RA serology testing identified 134 RA positive and 192 RA negative disease control individuals. Fifty healthy controls specimens were also included. Performance of anti-MCV and 14-3-3 eta, alone and combined with CCP3.1 and RF, was assessed. Anti-MCV had a sensitivity of 71 % and a specificity of 92 %. 14-3-3 eta had a sensitivity of 43 % and a specificity of 90 %. In comparison, CCP3.1 and RF displayed a sensitivity of 79 % and 84 % and a specificity of 92 % and 61 %, respectively. ROC curve analysis demonstrated CCP3.1 and anti-MCV had superior diagnostic performance compared to RF and 14-3-3 eta. In our cohort, anti-MCV and 14-3-3 eta failed to identify seronegative RA patients. Different combinations of double antibody positivity increased specificity at the cost of lost sensitivity. Individually, 14-3-3 eta, anti-MCV and CCP3.1 assays had≥90 % specificity in diagnosed RA patients, with better sensitivities for anti-MCV and CCP3.1 than 14-3-3 eta. Overall diagnostic performance of anti-MCV was similar to CCP3.1 and RF, all of which outperformed 14-3-3 eta in our cohort.

Clinical significance of anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis patients.

Anti-mutated citrullinated vimentin (MCV) antibodies have recently been recommended as a better arthritis diagnostic marker. To investigate the association between anti-MCV antibodies and the clinical, functional, and radiographic characteristics of rheumatoid arthritis (RA) patients. This case-control study was conducted on 40RApatients and 40healthy subjects. All patients were subjected to an assessment of disease using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), function by HAQ-DI, physical activity by International Physical Activity Questionnaire (IPAQ), fatigue by Functional Assessment of Chronic Illness Therapy (FACIT), serological tests as well as anti-MCV Abs measurement. A plain X-ray of both hands and wrists was done. The anti-MCV Abs level was significantly higher in RA patients than in healthy controls (P< 0.001). The anti-MCV Abs had a significant positive correlation with DAS, CDAI, HAQ, RF, Anti-CCP, and CRP (P= 0.006, 0.013, 0.005, < 0.001, < 0.001and 0.041respectively) and a significant negative correlation with FACIT (p= 0.007). Positive anti-MCV RA patients had significantly higher erosions, JSN, and a total sharp score. Anti-MCV Abs may contribute to poor physical activity and more fatigue in RA patients beyond their established role in disease activity and erosion.

Autoantibodies Serum Level and 10-Year Risk of Fractures Evaluated by FRAX® Tool in Rheumatoid Arthritis Patients.

FRAX® is a tool used for evaluation of risk of fracture in RA and non-RA patients and to identify those eligible for intervention. One of the limitations of FRAX in RA settings is that it does not consider factors known to contribute to osteoporosis such as autoantibodies. This study analysed the association of anti-mutated citrullinated vimentin antibody (anti-MCV), anti-cyclic citrullinated peptide antibody (anti-CCP), IgM rheumatoid factor (RF), IgA RF with 10-year risk of major osteoporosis and hip fracture. FRAX® tool was used to estimate 10-year risk of major osteoporosis fracture and hip fracture in 189 RA patients over 40 years of age. Anti-MCV, anti-CCP, IgM RF and IgA RF were tested using enzyme immunoassay and analysed at different levels. Results were adjusted for various confounders including disease activity. Fifty-one (26.9%) RA patients had high (≥20%) 10-year risk of major osteoporosis fracture and 67 (35.4%) had high (>3%) 10-year risk of hip fracture. Among all the tested autoantibodies, only IgM RF at elevated levels was associated with high 10-year risk of major osteoporosis fracture (adjusted OR = 4.1, 95% CI = 1.5-11.3, p = 0.006) and of hip fracture (adjusted OR = 17.4, 95% CI = 3.7-81.3, p < 0.0001). There was no agreement between FRAX and femoral neck (FN) BMD. None of the autoantibodies tested were associated with FN osteopenia or osteoporosis including IgM RF at high levels. Our study highlights the importance of quantitative measurement of autoantibodies in assessment of risk for fractures among RA patients. Our preliminary findings need to be assessed in prospective studies to determine the actual predictive value of high IgM RF levels among patients with RA.

Anti-mutated citrullinated vimentin antibodies are increased in IPF patients

IntroAn increased prevalence of serum anti-MCV antibody is observed in the serum of patients with idiopathic pulmonary fibrosis (IPF) but the clinical relevance of these antibodies is unknown. MethodsPatients from our center with a diagnosis of IPF according to the 2018 ATS/ERS/JRS/ALAT guidelines and at least one anti-MCV assay available were selected. All patients were part of the prospective cohort European IPF registry and selected between 03/2010 and 03/2018. We constituted two groups of patients according to the anti-MCV status at baseline to compare their characteristics at baseline and the evolution of lung function, survival and/or transplantation status. ResultsAnti-MCV data were available for 101 patients, of whom 86 had complete clinical data available. Twenty-nine (34 %) patients had a positive anti-MCV assay (MCV+), at a low level in most patients (29 UI/mL [IQR 25—40]), and 57 (66 %) patients a negative assay (MCV-). MCV+ patients were 20 men and 9 women, with a median age of 73 years [IQR 67—78]. MCV- patients were 49 men and 8 women with a median age of 72 years [IQR 64—77]. Sixty-two (75 %) patients were ex-smokers and 5 (6 %) were active smokers. Median cumulative tobacco smoke exposure was 22.5 (15.0–38.6) and was similar in both groups. Lung function test results and HRCT pattern distribution was similar in both groups at baseline. The median duration of follow-up was 3.5 years [IQR 2.1—5.0]. Lung function decline was similar in both groups. During the study period, 31 (36 %) patients died or have been transplanted with no difference in transplant-free survival status between the two groups. ConclusionLow level anti-MCV autoimmunity was prevalent in IPF patients

Risk Factors Analysis for the Development of Hypocomplementemia in Rheumatoid Arthritis Patients: A Single-Center Retrospective Study.

The purpose of the research was to explore the possible risk factors for the development of hypocomplementemia (HC) in rheumatoid arthritis (RA) patients by analyzing their clinical and laboratory features. This retrospective research contained 501 RA patients, divided into RA patients with HC (n=78) and RA patients without HC (n=423). Demographic characteristics and laboratory test results of RA patients were collected and analyzed, such as age, sex, anti-mutated citrullinated vimentin antibody (Anti-MCV), serum complements (C3, C4), immunoglobulins (IgA, IgG, IgM), hemoglobin (Hb), platelets (PLT) and erythrocyte sedimentation rate (ESR), etc. Spearman correlation was served as assessing the correlations of the levels of serum C3 and C4 with each index. Receiver operating characteristic (ROC) curves were served as assessing the diagnostic efficacy of each index for RA patients with HC. Furthermore, risk factors for the occurrence of HC in RA patients were analyzed by employing binary logistic regression of single and multiple factors. Compared RA patients with HC to without HC, the former were older and had a longer disease duration with increased levels of Anti-MCV, IgM and DAS28 and lower levels of Hb, PLT and ESR; Spearman correlation analysis verified the level of serum Anti-MCV was a negative correlation with C3 (r=-0.156); the area under the ROC curve (AUC) of PLT in diagnosing RA patients with HC was the largest at 0.65 (95% CI: 0.60-0.69); binary logistic regression analysis indicated that advanced age (>66 years), long disease duration (>62 months), high DAS28 value (>6.13), the levels of Anti-MCV>107.68IU/mL, IgM>1.54g/L, ESR≤69.00mm/h, Hb≤99.00g/L and PLT≤305.00×109/L were probable risk factors for the occurrence of HC in RA patients. Age and disease duration, DAS28, Anti-MCV, IgM, ESR, Hb, and PLT are closely related to the development of HC in RA patients. Timely monitoring of these indicators can help to evaluate disease activity of RA patients and further improve their prognosis.

VEXAS syndrome mimicking lupus-like disease.

Dear Editor, We report on an 81-year-old male Caucasian patient, who initially presented with oral ulcerations and disseminated erythematous papules on the upper back, chest, arms and legs with histopathological evidence of lymphocytic infiltration and small vessel vasculitis matching subacute lupus erythematous (Fig. 1A and B). His skin manifestations improved with topical CS and HCQ at standard dosages. However, a complete remission of the lesions could not be achieved. Therefore, repeated skin biopsies were performed, showing features of subacute eczema or Sweet Syndrome. Fourteen months later, the patient developed recurrent episodes of oral ulcerations, painful auricular and nasal erythematous swelling and arthritis in hands and feet (Fig. 1C and D). A hand MRI showed a moderate to severe wrist joint synovitis. Another 6 months later, he presented with clinical symptoms and laboratory findings of anaemia with increased, corpuscular volume (102.9 fl; normal range 81–98 fl), leukopoenia, lymphopenia, thrombocytopenia, increased levels of CRP, serum amyloid A and IL-6 as well as anti-mutated citrullinated vimentin (MCV) antibodies (Fig. 1G). Treatment with MTX was started at 15 mg/week and was well tolerated, leading to improvement of skin and joint symptoms. The patient experienced one episode of epilepsy with generalized convulsions. Cerebral MRI scan showed unspecific cerebral microangiopathy but no specific lesion. To rule out further foci of inflammation, an 18-fluorodeoxyglucose (18FDG)-PET/CT was performed, showing an enhanced FDG uptake typical for bone marrow activation (Fig. 1E and F), in accordance with a previous description [1]. Over the last 6 months, his skin and joints were well controlled by MTX. However, haematological and inflammatory parameters did not improve. As the patient fulfilled the major diagnostic traits of VEXAS [2], including male sex, increased corpuscular volume >100 fl and low platelets G/l, genetic testing was done. This patient was identified to carry the pathogenic variant c.121A>C, p. (Met41Leu) in exon 2 of UBA1 (NM_003334) (ACMG class 5) in mosaic state (68% of 93 reads), confirming the diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.

Anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis; diagnostic utility and association with deformities and disease activity

Rheumatoid arthritis (RA) is a chronic autoimmune disease with multiple morbidity burdens. Early diagnosis of RA is the main key in management and prevention of disease complications. Much research nowadays is looking for a serological marker with high accuracy in diagnosis of early RA cases. Our aim in this study was to evaluate the role of anti-mutated citrullinated vimentin (anti-MCV) antibodies in the early diagnosis of RA. In addition to compare its diagnostic sensitivity and specificity with anti-cyclic citrullinated peptide antibodies (anti-CCP) and RF antibodies in early versus established RA patients. This prospective cross-sectional study included 80 participants: 40 RA patients (20 early RA patients and 20 established RA patients), 20 patients with other rheumatic diseases (as a disease control group), and 20 apparently healthy participants as normal controls. All participants underwent history taking, clinical examination (general, articular assessment and calculation of disease activity score (DAS28-ESR)) for RA patients, radiological and laboratory investigations (RF, anti-CCP2 and anti-MCV antibodies measurements by ELISA technique). The results showed that the mean values of anti-CCP2 and anti-MCV were significantly increased in RA cases compared to the control groups (p=0.00 and p=0.01, respectively). Anti-MCV had sensitivity and specificity of 63% and 83%, respectively for diagnosing of early RA at area under curve of 0.80 compared to sensitivity and specificity 37% and 100%, respectively for anti-CCP2. Also, both (anti-CCP2 and anti-MCV) had positive significant correlations with ESR (p < 0.001 and p=0.02, respectively), CRP (p=0.01 and p=0.02, respectively) and DAS 28 (p < 0.001 for both). In conclusion, our data indicated that anti-MCV antibodies may represent a valuable marker for diagnosis of early RA cases.

Tumor necrosis factor-alpha stimulated gene-6: A biomarker reflecting disease activity in rheumatoid arthritis.

BackgroundTo explore the serum tumor necrosis factor‐alpha stimulated gene‐6 (TSG‐6) level and its association with disease activity in rheumatoid arthritis (RA) patients.MethodsWe recruited 176 RA patients, 178 non‐RA patients (lupus erythematosus, osteoarthritis, ulcerative colitis, ankylosing spondylitis and psoriasis) and 71 healthy subjects. Serum TSG‐6 levels were detected by enzyme‐linked immunosorbent assay (ELISA). RA patients were divided into inactive RA and active RA groups by disease activity score of 28 joints based on C‐reactive protein (DAS28‐CRP). The receiver operating characteristic (ROC) curve and Spearman's rank correlation test analyzed the correlation between TSG‐6 concentration and RA disease activity.ResultsTumor necrosis factor‐alpha stimulated gene‐6 levels in the RA group were increased (p < 0.01). TSG‐6 concentrations indicated an upward tendency with increased disease activity; The area under the curve (AUC) of TSG‐6 for diagnosing RA and assessing the severity of RA were 0.78 and 0.80, respectively; The combination of TSG‐6 and anti‐mutated citrullinated vimentin antibodies (anti‐MCV) (sensitivity:98.4%)improved the diagnostic accuracy of RA. Binary logistic regression analysis showed that TSG‐6 was an independent risk factor related to the severity of RA, and OR (95% CI) was 1.2 (1.003–1.453).ConclusionThe TSG‐6 levels in RA patients were elevated and related to disease activity. Therefore, TSG‐6 may serve as a new potential biomarker for evaluating RA disease activity.

Predictive value of anti-mutated citrullinated vimentin antibody on one-year radiographic progression in patients with rheumatoid arthritis

Objective: To investigate the value of baseline anti-mutated citrullinated vimentin (MCV) antibody for predicting one-year radiographic progression in patients with rheumatoid arthritis (RA). Methods: Consecutive RA patients were recruited from November 2014 to July 2018 at Department of Rheumatology, Sun Yat-sen Memorial Hospital, Clinical data were collected including disease activity score in 28 joints with four variables including C-reactive protein (CRP).Serum anti-MCV antibody at baseline was detected by enzyme-linked immunosorbent assay. X ray assessment of both hands/wrists was performed and assessed according to the Sharp/van der Heijde modified score (mTSS) at baseline and the 12th month. Univariate and multivariate logistic regression analyses were used to identify the risk factors for one-year radiographic progression. Results: Among 220 RA patients recruited, the positive rate of anti-MCV antibody at baseline was 77.7%. Compared with those with negative anti-MCV antibody, RA patients with positive anti-MCV antibody had higher disease activity score in 28 joints with four variables induding CRP [3.8 (2.4, 5.0) vs. 3.1 (2.1, 4.0), P=0.007], more physical dysfunction (21.6% vs. 8.2%, P=0.033) and higher radiographic indicators including mTSS [11 (2, 27) vs. 4 (1, 10), P=0.003], joint space narrowing [JSN, 4 (0, 14) vs. 2 (0, 6), P=0.024] and joint erosion[JE, 5 (1, 18)vs. 3 (0, 5), P=0.003]. After one-year follow-up, sixty-six RA patients (30.0%) developed radiographic progression, the percentage of whom was significantly higher in positive anti-MCV group than that in negative anti-MCV group (33.9% vs.16.3%, P=0.018). Multivariate logistic regression analysis suggested that positive anti-MCV antibody at baseline was an independent risk factor for one-year radiographic progression (OR=2.341, 95%CI 1.002-5.469). Conclusion: Positive anti-MCV antibody at baseline predicts one-year radiographic progression in RA patients. In the future, anti-MCV antibody can be used not only as a supplementary laboratory marker, but also in disease activity assessment and prognosis prediction for RA.

ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES VERSUS ANTI-MUTATED CITRULLINATED VIMENTIN ANTIBODIES IN JUVENILE IDIOPATHIC ARTHRITIS

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood and is of unknown etiology. Anti-cyclic citrullinated peptide antibodies (Anti CCP) and anti-mutated citrullinated vimentin antibodies (Anti MCV) may help in diagnosis of JIA. Objective: Measurement of anti CCP and anti MCV level in JIA patients, and healthy persons to assess its possible role in diagnosis. Patients and methods: This study included 70 patients with JIA, and 20 healthy volunteers with matched age and sex. We assessed serum anti CCP and anti MCV level in both groups by enzyme linked immunosorbent assay (ELISA). This study carried out over a period from July, 2019 to December, 2019. Results: Serum anti-CCP and anti-MCV level showed a statistical significant difference between control and patient groups. Conclusion: Anti-CCP as well as anti-MCV antibodies may be helpful in the diagnosis of JIA and should clearly be taken into consideration.

Value of serum collagen triple helix repeat containing-1(CTHRC1) and 14-3-3η protein compared to anti-CCP antibodies and anti-MCV antibodies in the diagnosis of rheumatoid arthritis

ABSTRACT Introduction Serological markers are important in the diagnosis of rheumatoid arthritis (RA) and other connective tissues diseases This study explored the clinical value of collagen triple helix repeat containing-1 (CTHRC1) and 14-3-3η protein, compared to routine markers, in the diagnosis of RA. Methods We recruited 103 RA patients, 105 non-RA patients (osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus) and 59 healthy controls. CTHRC1, 14-3-3η, anti-cyclic citrullinated peptide antibody (anti-CCP), anti-mutated citrullinated vimentin antibody (anti-MCV), rheumatoid factor and erythrocyte sedimentation rate (ESR) levels were measured, and their diagnostic value for RA evaluated and compared. Results All laboratory indices were elevated in RA (P < 0.05). Of these, anti-MCV had the highest sensitivity (86.4%) and anti-CCP the highest specificity (94.5%). The areas under the curve (AUC) of CTHRC1, 14-3-3η, anti-CCP, anti-MCV, rheumatoid factor and ESR were 0.84, 0.81, 0.89, 0.91, 0.85 and 0.77 respectively (all P < 0.01). Anti-CCP and anti-MCV were the most valuable in the diagnosis of RA. The combination of anti-CCP and anti-MCV had the maximum Youden index, followed by the combination of anti-CCP and 14-3-3η. Binary logistic regression analysis showed that 14-3-3η had the largest odds ratio value (95% CI) at 5.1 (2.1–12.5) for RA. Conclusion CTHRC1 and 14-3-3η are promising serological indicators of RA, and when combined with anti-CCP, anti-MCV and ESR, can improve the diagnosis of this disease.

Serum cytokine profile in early and established rheumatoid arthritis

Background:An important characteristic of immune pathology in rheumatoid arthritis (RA) is a B-cell tolerance defect, associated with autoantibodies production, and antigen-specific activation of Th-1 CD4+ T lymphocytes with an excess production of pro-inflammatory cytokines compared to anti-inflammatory ones. Pro-inflammatory cytokines contribute to the development of local inflammatory effects, induce bone destruction and pannus formation, and contribute to the development of autoimmune abnormalities and systemic manifestations. Anti-inflammatory cytokines are able to reduce the rate of joint destruction. There is evidence of the involvement of Th2 cytokines in the development of early RA. These facts suggest the need for a thorough investigation into the balance between the Th1 and Th2 types of immune response at different stages of the disease.Aim:To assess the importance of сytokine profiling in the evaluation of immune abnormalities in RA.Materials and methods:In this descriptive, controlled, retrospective study, we examined 118 patients with RA and 33 healthy donors as a control group. Serum IgM rheumatoid factor (RF) and C-reactive protein (CRP) levels were measured by immunonephelometry; anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) were determined by an enzyme immunoassay, cytokines levels with "xMAP" technique.Results:Serum cytokine levels vary depending on RA duration. The cytokine profile in early RA, unlike that in established RA with a duration of more than 6 months, is characterized by higher levels of pro-inflammatory (MIP-1α), Th1 (IFN-γ), and Th17 (IL-17) cytokines, colony-stimulating factors (IL-7, G-CSF), and chemokines (IL-8, IP-10) (p &lt; 0.05 for all parameters). In established RA, the levels of pro-inflammatory (IL-1β, -6, -15, TNF-α), anti-inflammatory (IL-1ra, IL-10, IL-13, IL-5), Th1 (IL-2, IL-12), Th2 (IL-9) cytokines and colony-stimulating factors (G-CSF, GM-CSF) correlate with the concentrations of IgM RF and antibodies to citrullinated proteins (antiCCP, anti-MCV) (all p &lt; 0.05). There was also а correlation between CRP and pro-inflammatory (IL-1β, IL-6, TNF-α), Th1 (IL-12), Th2 (IL-5, IL-9) cytokine levels and between DAS28 and pro-inflammatory cytokine (IL-6) and colony-stimulating factor (G-CSF) levels (all p &lt; 0.05).Conclusion:In RA, cytokines, chemokines and colony-stimulating factors mirror the inflammatory activity of the disease. Changes in blood concentrations of cytokines enable to get an insight into the complex interplay of numerous mediators of innate and acquired immunity

Clinical diagnostic significance of 14-3-3η protein, high-mobility group box-1, anti-cyclic citrullinated peptide antibodies, anti-mutated citrullinated vimentin antibodies and rheumatoid factor in rheumatoid arthritis

ABSTRACTIntroduction: Circulating markers of rheumatoid arthritis (RA) include the 14–3-3η protein, high-mobility group box-1 (HMGB1), anti-cyclic citrullinated peptide (anti-CCP) antibodies, anti-mutated citrullinated vimentin (anti-MCV) antibodies and rheumatoid factor (RF). We set out to determine which two markers in combination provided best discriminatory power for this disease.Methods: We recruited 108 RA patients, 102 non-RA patients (SLE, AS, Sjogren’s syndrome, MCTD) and 90 healthy controls. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and the Youden index of each analyte were calculated and binary logistic regression analysis and receiver operating characteristic (ROC) curve were performed to evaluate their diagnostic value for RA alone and in paired combination.Results: As expected, all markers were elevated in RA patients (P < 0.05). Binary logistic regression analysis showed that 14–3-3η had the highest odds ratio (95% CI) at 2.4 (1.9–2.8). Anti-CCP and anti-MCV had the highest areas under the curves [AUC (95% CI)] at 0.85 (0.78–0.90) and 0.85 (0.78–0.91) respectively (both P < 0.001). In serial detection (one marker followed by another), no combination had a Youden index >0.6. In parallel analysis (both considered together) several combinations had a Youden index >0.7, of which the highest (0.78) was anti-CCP with anti-MCV, with a sensitivity of 93.3% and specificity of 84.7%.Conclusions: Despite individual increases in serum 14–3-3η, HMGB1, anti-CCP, anti-MCV and RF, the combination of anti-CCP and anti-MCV might be of great help for diagnostic in RA, and so should be considered as routine tests for this disease.

Predicting factors for disappearance of anti-mutated citrullinated vimentin antibodies in sera of patients with rheumatoid arthritis

Objectives: We aimed to determine the predicting factors for disappearance of anti-mutated citrullinated vimentin antibody (anti-MCV Ab) in sera from rheumatoid arthritis (RA) patients.Methods: In 2013, 95 RA patients whose Disease Activity Score with erythrocyte sedimentation rate were moderate to severe (DAS28-ESR ≥3.2) at baseline were enrolled. Titers of anti-MCV Ab and anti-cyclic citrullinated peptide (anti-CCP) Ab for 2013 and 2014 were measured. The association of anti-MCV disappearance with disease activity, treatment, interstitial lung disease (ILD), and serum markers of ILD were retrospectively examined. Predicting factors of anti-MCV disappearance were determined by multivariable analysis.Results: While anti-CCP positivity rate did not change during the year, anti-MCV Ab changed from positive to negative in 18 patients (=19.0%). Continuous biological disease-modifying anti-rheumatic drug use, prednisolone dose (≥5.0 mg daily), and low KL-6 level (<191 U/mL) were determined as predicting factors of anti-MCV disappearance by multivariable analysis. In our cohort, anti-MCV Ab disappearance was not linked to clinical and radiological improvement.Conclusion: Different from anti-CCP Ab, anti-MCV Ab in sera from RA patients can disappear in a year. Some predicting factors for such negative seroconversion were found, whereas clinical significance of anti-MCV Ab disappearance was undetermined.

Anti-mutant citrullinated vimentin antibody in the diagnosis of rheumatoid arthritis

Objective This study aimed to assess the diagnostic value of anti-mutated citrullinated vimentin (MCV) antibodies in rheumatoid arthritis (RA) and its correlation with disease progression, extra-articular manifestations and overlap syndrome. Methods Retrospective Studies. Clinical data of 837 patients in PekingUnionMedicalCollegeHospitalfrom June to August 2017 were collected, including the result of anti-MCV, anti-cyclic citrullinated peptide (anti-CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and High-sensitivity-C-reactive protein (CRP). According to the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis, there were 323 patients diagnosed with RA, including 59 males and 264 females with the average age of 51 years. According to whether the RA patients have overlap syndrome with other autoimmune disease (AID) or have extra-articular manifestations, 258 cases were categorized into RA group, including 47 males and 211 females with the average age of 50 years; 14 cases were categorized into the group of overlap syndrome, including 1 male and 13 females with the average age of 36 years; 51 cases were categorized into the group of extra-articular manifestations, including 11 males and 40 females with the average age of 59 years.According to 2010 rheumatoid arthritis classification criteria for destruction in joints, the radiographic changes were divided into 4 stages.There were 203 casesenrolled in our study, 88 caseswere fitted into early stage group (stage I)including 21 males and 67 females with the average age of 48 years; 115 caseswere fitted into progressive stage group, which compromisedstageⅡ (interim stage), stage Ⅲ (severe stage) and stage Ⅳ (final stage) cases, including 19 males and 96 females with the average age of 53 years. Mann-Whitney U test, χ2 test,Receiver operating characteristic (ROC) curves and Spearmancorrelation coefficientwere used in Statistical analysis. Results Ⅰ Amongdiagnosed RA patients, 199 (61.6%) cases were positive for anti-MCV, anti-CCP and RFsimultaneously, 42 (13%) cases were positive for anti-MCV, which was higher than anti-CCP positive (1 cases, 0.3%) or RF positive (7cases, 2.2%). The difference was statistically significant(P<0.001, P<0.001). Ⅱ ROC was calculated and MCV=35.95 U/ml was used as best-fit cut-off value. The AUC for anti-MCV was 0.867, while the sensitivity was 80.5% and specificity was 80.9%. Ⅲ The detection levels of anti-MCV (682.8 (106.4-1000.0)), anti-CCP (407 (4.0-1536.0)) and RF (82.8 (21.1-244.9)) in the group of progressive stage were higher than those in the group of early stage (114.5 (28.5-1000.0), 62.5 (5.0-1020.7), 50.1 (6.7-127.1)), which showed a significant difference (P<0.05, P<0.05, P<0.05). The anti-MCV, anti-CCP and RF were positively related to the degree of joint destruction (r=0.229, P<0.05; r=0.187, P<0.05; r=0.167, P<0.05); anti-MCV and anti-CCP were positively related to extra-articular manifestation (r=0.152, P<0.05; r=0.136, P<0.05). Conclusion Anti-MCV antibodies are more sensitive in patients with RA, and have complementary diagnostic value for anti-CCP and RF-negative patients; high levels of anti-MCV and anti-CCP in RA patients are associated with RA progression and extra-articular involvement. Key words: Arthritis, rheumatoid; Autoantibodies; Peptides, cyclic; Vimentin

Autoantibody and metalloproteinase activity in early arthritis

ObjectivesThe aim of the study was to evaluate the frequency of anti-mutated citrullinated vimentin antibodies (a-Sa), anti-citrullinated α-enolase peptide 1 antibodies (a-CEP-1), anti-filaggrin antibodies (AFAs), heterogeneous nuclear ribonucleoprotein compies/anti-RA33-antibodies (a-hnRNP/RA33), anti-carbamylated protein antibodies (a-CarP), and metalloproteinase (MMPs) activity in patients with early inflammatory arthritis (EIA).MethodsSeventy-four patients with EIA: 51 diagnosed with RA (rheumatoid arthritis) and 23 with UA (undifferentiated arthritis), and 20 healthy volunteers were enrolled to the study. Inflammatory markers, rheumatoid factor (RF), and antibodies mentioned above were assessed in all patients.ResultsIn the EIA group, we observed significantly higher concentration of a-CEP-1 (65.8 ± 111.6 RU/mL) than in controls (2.0 ± 0.0 RU/mL). In RF(+) RA patients, we observed higher concentration of a-Sa and a-CEP-1 than in other groups. A-Sa were positive in 69% of RF(+) RA, 37% of RF(−) RA, 26% of UA patients and in 10% of controls. A–CEP-1 were positive in 77% of RF(+) RA patients, in 56% of RF(−) RA patients, in 8.7% of UA patients, but they were negative in controls. In patients with RF(+) RA, positive a-CarP were present statistically significantly more often than in RF (−) RA patients. No statistically significant difference in frequency of a-hnRNP/RA33 and AFA between RF(+) RA, RF(−) RA, and UA was observed.ConclusionsOur results suggest that a-CEP-1 may help in differentiation between RF(−) RA and UA. a-CEP-1 and a-Sa may be useful while diagnosing EIA. a-CarP may be used in differentiation of RA RF(−) and UA. However, a follow-up study is needed to evaluate the prognostic value of analyzed antibodies.

Evaluation of disease activity markers in relation to dry eye disease in patients with rheumatoid arthritis

PurposeThe aim of this study was to correlate the presence of anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) antibodies with rheumatoid disease activity and dry eye disease in patients with rheumatoid arthritis (RA).Patients and methodsA total of 69 patients were evaluated for the activity of RA using the Disease Activity Score (DAS-28), erythrocyte sedimentation rate, and C-reactive protein. We used the Health Assessment Questionnaire-Disability Index to assess functional disability. Anti-CCP and anti-MCV antibodies were measured using enzyme-linked immunosorbent assay technique. We assessed dry eye symptoms using Ocular Surface Disease Index (OSDI) questionnaire. Clinical tests used for dry eye assessment included Schirmer’s test, tear breakup time test, and ocular surface fluorescein staining.ResultsAnti-CCP antibody serum levels significantly correlated with DAS (r=0.46, P=0.036), Schirmer’s test (r=0.40, P=0.038), and ocular surface fluorescein staining (r=0.6, P=0.04). Anti-MCV antibody serum levels correlated with DAS (r=0.5, P=0.04), ocular surface fluorescein staining (r=0.9, P=0.007), and OSDI score (r=0.3, P=0.03). DAS showed a nonsignificant correlation with OSDI score and all tests of dry eye. OSDI score significantly correlated with Schirmer’s test (P=0.036).ConclusionDry eye is the most common ocular manifestation in our investigated patients with RA. Dry eye disease existence is not correlated with disease activity, hence all patients with RA should be regularly examined for dye eye regardless of disease severity. Rheumatologists could use the OSDI questionnaire for screening dry eye disease in patients with RA. The presence of anti-CCP and anti-MCV antibodies may denote the existence of dry eye disease and correlates with RA disease activity.

Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis in comparison with other rheumatic diseases; a nephrology point of view

Introduction: Rheumatoid arthritis (RA) is one of the most common autoimmune rheumatic disease with a chronic and progressive inflammatory disorder manifestations leading to articular cartilage damage, and disability, and also renal involvement. It seems that recruitment of tests based on high specific and sensitive serological immunobiomarkers removes these mentioned gaps. Additionally, the results of laboratory tests, assist to reach an accurate prognosis and real estimation of the patient’s clinical statue especially hospitalized individuals in intensive care units. Objectives: The aim of this study is assessment and titration of some autoantibodies as anti-mutated citrullinated vimentin (anti-MCV), anti-cyclic citrullinated peptides (anti- CCP), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in RA patients in comparison to patients with other forms of rheumatologic diseases. Patients and Methods: This descriptive study was conducted from January to June 2012 in Zanjan province on 100 patients with RA and 100 patients with other rheumatic disease that were randomly selected. All necessary data of clinical history for the patients was extracted from their medical records. After delivering antecubital venous blood (7 mL) to hematology ward of laboratory, quantative ELISA test was performed for autoantibodies. Results: Anti-MCV tests showed 72% positivity in RA group compared to 10% positivity in other group of rheumatic diseases. There was a significant correlation between positivity of anti-MCV and RA disease. Mean anti-MCV titer is 236.23 ± 2.319 U/mL in RA group and 28.75 ± 0.432 U/mL in other disease group. In this study anti-MCV antibodies had diagnostic sensitivity of 81.7% (versus anti-CCP), diagnostic specificity of 72.22%, positive and negative predictive value 93.05% and 46.42%, respectively. Conclusion: According to results of this study, not only anti-MCV measurement but also anti-CCP assist to early diagnosis of RA. Results of the recent study could not show definite correlation between anti-MCV and disease activity. The result of this study may be helpful for renal involvement in RA patients, whereas evaluation on this aspect of RA patients seems essential.