anti-MCV Research Articles

Porphyromonas Gingivalis - A Periodontal Pathogen with Potential Role in Rheumatoid Arthritis and its Association with Anti-CCP and Anti-MCV Antibodies Positivity

Background: In recent studies, a strong association between rheumatoid arthritis (RA) and chronic periodontal disease (CPD) has been identified, indicating common disease pathogenesis and risk factors. One of them is the presence of the pathogen Porphyromonas gingivalis (PG), which can initiate the process of citrullination, by secreting the enzyme Porphyromonas Peptydil Arginine Deminase (PPAD).
 The aim of the study is to show the presence of PG in RA patients, and to evaluate the association of the PG presence with anti-citrullinated proteins/peptides (ACPA) positivity i.e. anti CCP and anti MCV positivity.
 Methods: The study included 80 participants - 30 patients which fulfilled 2010 ACR/EULAR RA classification criteria and 50 controls, which were genetically analyzed for the presence of PG by Chelex®100 method and polymerase chain reaction (PCR) and for the presence of anti CCP and anti MCV autoantibodies with the ELISA method.
 Results: Twenty out of thirty RA patients (80 %) and 16 out of 50 controls (32%) were positive for PG. (χ 2 = 11.461, p <0.001 for OA and χ2 = 13.91, p <0.001 for HC). Of the PG-positive RA patients, 83% had positive anti-CCP and 79% had positive anti-MCV test. The odds ratios OR of 25 and 19 were statistically significant (p = 0.008 and p =0,014 respectfully).
 Conclusions: PG was present more frequently in RA patients and there was a statistically significant association with anti CCP and anti MCV antibodies.

MO223MEMBRANOUS NEPHROPATHY ASSOCIATED TO ANKYLOSING SPONDYLITIS: CASE REPORT

Abstract Background and Aims Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic disease diagnosed by the presence of the HLA-B27 antigen with joint and extra-articular manifestations. Its pathogenesis was initially based on auto-inflammatory phenomena, mainly involving innate immunity. However, many studies carried out in the recent years focus on its adaptive immunity aspect, especially autoimmune. These mechanisms seem to interact with each other, resulting in a complex pathophysiology. The general autoimmune characteristics of AS were investigated by Yuan and al, who reviewed recent reports of autoantibodies levels in AS patients. Their analysis shows that none of the autoantibodies considered in the study meet the criteria to be considered as a biomarker for the disease (including antibodies Anti- :CD74; beta2-Microglobulin; mutated Citrullinated Vimentin (MCV); Heat Shock Protein 65 (HSP65); 14-3-3 eta autoantibodies (14-3-3η); 1A-dependent autoantibody magnesium anti-protein phosphatase (PPM1A); sclerostin (SOST); and Anti-microbial antibodies). Renal involvement in AS is dominated by amyloidosis and IgA nephropathy. In rare cases, this disease has been associated with Membranous Nephropathy (MN). The pathogenetic link between the two disorders remains obscure. However, the recent connection of AS to autoantibodies potentially indicates the involvement of immune complexes formed from these autoantibodies in the development of MN. Method We report the case of a 36-years-old woman with a 7 years history of sacroiliitis, who also developed a pedal edema in May 2020. AS was diagnosed in 2014 by the presence of positive HLA-B27, and clinical and radiological manifestations of bilateral sacroiliitis without extra renal manifestations treated by indometacin during periods of pain . A pure nephrotic syndrome was revealed with a 24h proteinuria of 12g / 24h.The patient’s Albumin levels were at 16g/l, without HTA or hematuria, and with a correct renal function (Creatinine at 60mmol/l). A renal biopsy showed a MN with type I polytypical. Light microscopy showed a thickening of capillary loops, while IF staining revealed granular deposits of IgG along the capillary wall. Investigations of further secondary MNs were negative, and the patient was aPLA2R-negative. Results A treatment by corticosteroids was initiated prior biopsy to her referral , which resulted in pain relief and urinary protein reduction (prot 24h 1.5g/24h). Given her good response to this initial treatment, corticotherapy was maintained. As the levels of inflammation and discomfort were low, the patient did not wish to be treated by biotherapy. Conclusion This case suggests a secondary MN in association with AS.The discovery of new autoantibodies associated with AS opens up promising perspectives, and could potentially lead to the characterization of biomarkers for screening and monitoring this disease. However, more studies are needed in order to improve our understanding of the role played by possible immune complex diseases, (in particular MN), in relation to this Ankylosing spondilitis.

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.

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

Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vimentin.

Periarticular bone loss is a long known but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering periarticular bone loss. Periarticular bone loss was studied in the standard antigen-induced arthritis (AIA) mouse model with methylated bovine serum albumin (mBSA) as well as a modified model with mutated citrullinated vimentin (MCV) alone or in combination with mBSA. Periarticular bone loss, subchondral osteoclastogenesis, as well as local expression of cytokines, osteoclast genes, and peptidyl-arginine deiminase (PAD) enzymes were assessed after arthritis induction. Immune cell and osteoclast precursor infiltration were detected in the periarticular bone marrow and local lymph nodes. In addition, periarticular bone loss was assessed upon challenge of mice with purified anti-MCV antibody. Despite inducing a milder form of arthritis than mBSA, MCV triggered significant periarticular bone loss associated with an increased infiltration of osteoclast precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced the expression of the osteoclast inducers RANKL and M-CSF, the cytokines IL-8, IL-1, IL-6, and TNF-α, as well as PAD2 and PAD4 enzymes in the periarticular bone marrow. Furthermore, also anti-MCV antibody challenge induced significant periarticular bone loss and local osteoclastogenesis in the mice. Autoimmunity against citrullinated vimentin triggers periarticular bone loss by osteoclast activation in the bone marrow. These findings may explain why periarticular bone loss is already found very early in the disease course of patients with rheumatoid arthritis. © 2017 American Society for Bone and Mineral Research.

Anti CCP and Anti MCV Antibodies are Marker of Arthritis in Systemic Lupus Erythematosus and Scleroderma

Anti CCP and Anti MCV Antibodies are Marker of Arthritis in Systemic Lupus Erythematosus and Scleroderma

Diagnostic value of autoantibodies combined detection for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disease, there are many autoantibodies produced during disease progression in the patients' serum, and this work is to select a best detection scheme for RA diagnosis. Autoantibody levels including rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), mutated citrullinated vimentin (MCV), anti-keratin antibodies(AKA), anti-perinuclear factor (APF), and Ig heavy chain binding protein (BIP), were measured, and the sensitivity, specificity, predictive values, accuracy, and Youden's index of different combining forms were all calculated in RA patients, disease, and healthy control group. The differences in the positive rates of the three groups were compared between any two of them. Generally speaking, the sensitivity of the autoantibodies detected in parallel combination was higher than that in tandem, which was more specific. The sensitivity of anti-MCV and RF calculated in parallel (87.61%) was obviously better than that of anyone autoantibody (P<.05), and only increased slightly even if more autoantibodies were tested in parallel (P>.05). The specificity of anti-CCP and BIP measured in tandem (95.92%) was obviously higher than that of anyone autoantibody (P<.05). While increasing the detected number of autoantibody from two kinds to three or more, the specificity was improved insignificantly (P>.05). Anti-BIP and CCP antibodies detected in tandem combination can obtain higher specificity, and have good clinical value for the differential diagnosis of RA.

Anti CCP and Anti MCV antibodies in Rheumatological disorders other than Rheumatoid arthritis

Anti CCP and Anti MCV antibodies in Rheumatological disorders other than Rheumatoid arthritis

Separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline- and homocitrulline-containing peptides related to type I and II collagen telopeptides.

IntroductionOur objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence.MethodsA total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked immunosorbent assay to citrulline- or homocitrulline-containing type I and II collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide (CCP) and to mutated citrullinated vimentin (MCV). Specificities of the antibodies were tested using inhibition-ELISA.ResultsOf the RA sera, 39 (54%) and 41 (57%) were positive for binding to CCP and MCV, respectively. Further, 34 (47%) and 30 (42%) of the patients had specific antibodies binding to and being inhibited by citrulline-containing type I collagen telopeptides and by citrulline-containing type II collagen carboxyterminal telopeptides, respectively. The corresponding figures regarding homocitrulline-containing type I and homocitrulline-containing type II collagen telopeptides were 16 (22%) and 14 (19%). Most of the patients, who were seropositive for citrullinated peptides, showed binding in multiple assays. A total of 10 (14%) RA patients were positive for all the tested peptide pairs, while 28 (39%) of them had antibodies that contained overlapping specifities between citrulline and homocitrulline in the same peptide sequence.ConclusionsAntibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients. These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals. Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0515-z) contains supplementary material, which is available to authorized users.

Diagnostic value of anti-MCV antibodies for ankylosing spondylitis

Objective To investigate the diagnostic value of anti-mutated citrullinated vimentin（anti-MCV） and anti-cyclic citrullinated peptide（anti-CCP） antibodies for ankylosing spondylitis (AS), and to establish a new diagnostic method of AS based on anti-citrullinated protein/peptide antibodies（ACPAs） detection. Methods Totally 121 AS patients(AS group), 97 rheumatoid arthritis（RA） patients(RA group)and 103 healthy people(control group) were enrolled for the detection of serum levels of anti-MCV and anti-CCP antibodies using ELISA method as a diagnostic test. HLA-B27 in AS patients was tested by flow cytometry, and RF-IgM in RA and AS patients was detected by immune rate nephelometry. Receiver operating characteristics (ROC) curve was used to analyze the diagnostic value and to determine the cut-off value. Anti-MCV and anti-CCP antibodies among each group were compared by Mann-Whitney U test, Chi-square test or Fisher′s exact test was used to compare positive rate. Results The anti-MCV levels in AS group ［11.60 (12.36-25.83) U/ml］were significantly higher than control group ［11.60(8.41-13.54）U/ml ］,U=2 413,P<0.001, while the levels of anti-CCP had no difference between the two groups ［AS group 6.22 （4.30-8.07）U/ml］, and control group ［6.01(3.77-7.58)U/ml］, respectively; U=5 421,P=0.094. The calculated area under the ROC curve of anti-MCV was 0.806,and 14.67 U/ml was the optimal cut-off value with sensitivity of 0.645 and specificity of 0.942. In both HLA-B27 positive and negative AS patients, anti-MCV antibodies levels and positive rate were significantly higher than control group using new cut-off value above （U=133.5, P=0.001; U=2 279.5,P<0.001). Sensitivity of the combination detection of anti-MCV and anti-CCP (MCV+CCP－) or RF-IgM (MCV+RF－) were 60.3% (73/121), 62.8% (76/121) and specificity were 89.7% (87/97), 90.7% (88/97) respectively in differential diagnosis of AS and RA, which were significantly higher than anti-MCV detection alone in specificity (16.5%,16/97). Conclusions Anti-MCV could be a new biomarker for the diagnosis of AS. With high sensitivity and specificity, anti-MCV has an equal diagnostic efficiency in HLA-B27 positive and negative AS patients using our new cut-off value. Additionally， the combination detection of anti-MCV and anti-CCP or RF-IgM could be an effective method for differential diagnosis of AS and RA.（Chin J Lab Med,2014,37: 455-458） Key words: Spondylitis,ankylosing; Peptides,cyclic; Vimentin; Mutation; Rheumatoid factor

AB1243 Comparison of the sensitivity and specificity of ACCP and anti MCV in rhematoid artheritis patients

BackgroundRheumatoid arthritis is a systemic inflammatory disease that mainly affects small joints. It has a destructive potential, then early diagnosis and treatment can prevent deformities and extra articular manifestations. According...

SAT0102 Epitope mapping for MCV peptides and subclass of anti-MCV antibodies is a useful tool for the prediction of response to B-cell directed therapy in rheumatoid arthritis

BackgroundIn patients with rheumatoid arthritis (RA), seropositivity for either rheumatoid factor or anti-CCP antibodies has been identified as a predictive marker for treatment response to rituximab (RTX) in different studies....

OP0019 Anti-citrullinated protein antibodies directly induce bone loss in rheumatoid arthritis

BackgroundAutoantibodies against citrullinated proteins (ACPA) are amongst the strongest risk factors for bone destruction in rheumatoid arthritis (RA)ObjectivesWe therefore hypothesized that these autoantibodies directly influence bone metabolism.MethodsA strong and specific...

Relationship of the HLA-DRB1 alleles and seropositivity, anti-MCV, functional status and radiological damage in Turkish patients with rheumatoid arthritis

The HLA-DRB1 gene plays an important role in the genetic predisposition to rheumatoid arthritis. The anti-citrullinated protein antibody (ACPA) is known to be associated with the susceptibility to rheumatoid arthritis (RA), as well as the severity of the disease. The aim of this study is to determine the HLA genes that are associated with the severity of the RA measured by seropositivity, functional status, radiological damage and the anti-modified citrullinated vimentin (MCV) levels. Ninety-six patients diagnosed with rheumatoid arthritis and a control group consisting of 84 healthy individuals were enrolled in the study. The HLA-DRB1 type and subtypes were specified using the polymerase chain reaction with sequence-specific primers (PCR-SSP). The association of the HLA-DRB1 type and subtypes with seropositivity, anti-MCV levels, functional status and anatomical joint damage were explored using the modified Larsen scoring method. The DRB1*01, DRB1*04, DRB1*07, DRB1*10, DRB1*11 and DRB1*15 alleles were found to be related with higher anti-MCV levels (p< 0.05). The DRB1*11 type and the DRB1*1001 subtype were observed to be associated with poor functional status (Stages 3-4). The DRB1*0801 subtype was associated with lower anti MCV levels (OR=8.35, p=0.02). DRB1*04 type and DRB1*0405 subtypes were related with radiological damage (OR=0.52 and 0.25; p=0.04 and 0.03, respectively). No significant relationship was observed between the RF seropositivity and the HLA-DRB1 alleles. This study revealed the association between the HLA alleles and seropositivity, functional status, anti-MCV levels and radiological damage in patients in the Southeast Anatolian region of Turkey.

Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin.

Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption in RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination, and specific N-terminal citrullination of vimentin was induced during osteoclast differentiation. Affinity-purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to osteoclast surfaces, but also led to robust induction of osteoclastogenesis and bone-resorptive activity. Adoptive transfer of purified human MCV autoantibodies into mice induced osteopenia and increased osteoclastogenesis. This effect was based on the inducible release of TNF-α from osteoclast precursors and the subsequent increase of osteoclast precursor cell numbers with enhanced expression of activation and growth factor receptors. Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.

Antibodies binding to citrullinated telopeptides of type I and type II collagens and to mutated citrullinated vimentin synergistically predict the development of seropositive rheumatoid arthritis

ObjectiveTo assess whether antibodies binding to citrullinated carboxy-terminal telopeptides of type I and type II collagens (TELO-I and TELO-II, respectively), mutated citrullinated vimentin (MCV) and cyclic citrullinated peptides (CCP) predict...

The diagnostic and monitoring value of serum anti-mutated citrullinated vimentin antibodies (anti-MCV) in juvenile rheumatoid arthritis

Background: JRA is currently diagnosed using the American College of Rheumatology (ACR) 1987 revised criteria that are primarily based on clinical parameters. The criteria may be insufficient for the diagnosis of early RA as they are based upon measurements of disease classification predominately featuring manifestations typical of later-stage disease. Measurement of serum anti-mutated citrullinated vimentin antibodies (MCV) has been shown to be a better marker for early adult RA, and it correlates well with the disease activity score (DAS). Objectives: The aim of this work is to evaluate the role of antimutated citrullinated vimentin antibodies (anti-MCV) in the diagnosis, and in monitoring disease activity in juvenile rheumatoid arthritis. Methods: The study included 40 children with JRA fulfilling the American College of Rheumatology criteria for diagnosis of JRA: 4 children with oligoarticular JRA, 12 with polyarticular JRA and 24 children with systemic onset JRA. Fifty healthy children, matching the patients in age and sex served as a control group. The studied children with JRA were subjected to laboratory tests including CBC, ESR, CRP, ANA and rheumatoid factor (RF). Serum samples from both patients and controls were assayed for anti-MCV levels using an ELISA technique. Results: The study showed high mean serum anti-MCV antibodies level in JRA patients when compared to controls (P= 0.00). In addition, there were no significant correlations between anti-MCV antibody levels and parameters of disease activity, namely, number of swollen joints, number of tender joints, ESR and CRP. The receiver operating characteristic (ROC) curve was drawn and it showed that the area under the curve (AUC) was (0.896). At a cutoff level > 17 u/mL, anti-MCV antibodies had diagnostic specificity of 88%, diagnostic sensitivity of 87.5%, negative and positive predictive values of 89.8% and 85.4%, respectively and diagnostic efficacy of 87.8%. We also reported 3/40 of JRA patients to be positive for RF and 2/40 of JRA patients to be positive for ANA. Conclusion: Measurement of serum anti MCV antibody level holds promise as a diagnostic tool in JRA. However, they failed to show a significant efficacy in determining disease activity. Keywords: Juvenile rheumatoid arthritis, MCV Egypt J Pediatr Allergy Immunol 2012;10(2):75-80

Optimization of the immunologic diagnostic criteria for rheumatoid arthritis

Objective To optimize the immunologic diagnostic criteria of rheumatoid arthritis commonly used in clinical,to find methods to diagnose rheumatoid arthritis quickly,accurately and economically.Methods The levels of RF,CRP,ESR,anti-CCP,AKA,CP I,anti-MCV in blood of the patients with rheumatoid arthritis were simultaneously measured, and their sensitivity and specificity was compared.Results The sensitivity and specificity of antiMCV was 76.8% and 90.6% ,anti-CCP 67.2% and 90.3% ,AKA 75.2% and 84.7% ,RF 72.8% and 79.1%.The sensitivity and specificity of them were higher.The specificity of GPI(92.1% ) was high,but the sensitivity of it (46.4% )was low.The sensitivity and specificity of other criteria were low.Conclusion anti-MCV,anti-CCP,AKA and RF could be preferentially used in the diagnosis,therapy and monitor of curative effect of rheumatoid arthritis. Key words: Rheumatoid arthritis; Diagnostic criteria; Optimizing

848 Anti-MCV and Anti-CCP Antibodies - Diagnostic and Prognostic Value in Children with Juvenile Idiopathic Arthritis

Background: Antibodies against cyclic citrullinated peptides (CCP) are useful for diagnosing Rheumatoid Arthritis and Juvenile Idiopathic Arthritis (JIA). Antibodies to mutated citrullinated vimentin (MCV) were recently described in Rheumatoid Arthritis in adults.The aim of the study was to evaluate the diagnostic and prognostic value of anti-MCV in JIA comparing to anti-CCP.Methods: 30 children (19 girls and 11 boys; aged 4 -18 years) with confirmed JIA diagnosis and 20 children as a control group were included into the study. Anti-CCP and anti-MCV antibodies in sera were measured using ELISA test.Results: Sensitivity and specificity of the anti-CCP were 40% and 100% compared with 36,7% and 90% for the anti-MCV calculated using manufactures recommended cut-off values.Anti-MCV were positive in 11/30 comparing with 12/30 for anti-CCP in children with JIA. Among 11 JIA children positive for anti-MCV, 5 were also positive for anti-CCP and among 18 JIA children negative for anti-CCP, 6 were positive for anti-MCV. Both antibodies were mainly observed in polyarthritis, however could be positive in other types of JIA.Anti-MCV serum concentration correlated positively with anti-CCP (p=0,0018). Anti-CCP correlated positively with disease activity (p=0,00196), radiological destruction in joints (p=0,00196) at baseline and after median 11,5 months of follow up (p=0,00961), but these correlations were not observed concerning anti-MCV (respectively: p=0,0657; p=0,06199; p=0,064).Conclusions: Anti-MCV as well as anti-CCP antibodies could be helpful in the diagnosis of JIA. However, the anti-CCP prognostic value in JIA appears to be superior to the anti-MCV test.

The impact of HLA-DRB alleles on the subclass titres of antibodies against citrullinated peptides

The association between HLA-DR haplotypes and RA have been well established. However, the molecular mechanisms of how HLA mediates susceptibility and/or progression of the disease remain elusive. We therefore turned to the RA-specific antibodies directed against citrullinated peptide antigens (ACPAs) and investigated the association between HLA-DRB1 shared epitope (SE) alleles and the IgG subclass titres of cyclic citrullinated peptide (CCP)- and mutated citrullinated vimentin (MCV)-specific antibodies. One hundred and twenty-seven RA patients were typed for their HLA-DRB1 haplotypes applying low resolution and alleles potentially carrying the SE were sequenced. All patients' sera were analysed by ELISA for the presence of ACPA and 77 patients positive for CCP-specific antibodies were further analysed for the respective IgG subclasses. Subclass titres were then correlated to the presence of a SE. Finally, all patients were screened for the HLA-DRB4-associated splice variant. We found a gene dosage effect of the HLA-DRB1*04-associated SE on both the MCV- and CCP-specific IgG3 levels. The HLA-DRB4-associated splice variant accumulates in ACPA-negative RA patients. Both the dose-dependent increase in IgG3 among ACPA and the accumulation of the splice variant in ACPA-negative patients imply differential expression of the HLA alleles as the mechanism contributing to the susceptibility and/or disease progression of RA. The preponderance of IgG3 hints at a skewing towards a Th1 response and is reminiscent of increased signal strengths at the immunological synapse. Likewise, the abrogation of HLA-DRB4 expression due to the splice variant reduces the signal strength and seems to protect from ACPA development.