Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis Comparison of Threshold Cutpoints and Continuous Measures of Anti-Cyclic Citrullinated Peptide Antibodies in Predicting Future Rheumatoid Arthritis Anti-perinuclear factor compared with the so called “antikeratin” antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritides Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset Diagnostic performance and predictive value of rheumatoid factor, anti-citrullinated peptide antibodies, and the HLA shared epitope for diagnosis of rheumatoid arthritis. [The role of anti-cyclic citrullinated peptide (anti-CCP) antibodies in serologic diagnosis and evaluation of disease activity in rheumatoid arthritis]. Diagnostic classification of spondylarthropathy and rheumatoid arthritis by synovial histopathology: a prospective study in 154 consecutive patients. Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy A prediction rule for disease outcome in patients with undifferentiated arthritis using magnetic resonance imaging of the wrists and finger joints and serologic autoantibodies. Usefulness of magnetic resonance imaging of the hand versus anticyclic citrullinated peptide antibody testing to confirm the diagnosis of clinically suspected early rheumatoid arthritis in the absence of rheumatoid factor and radiographic erosions. Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis Predictive value of antibodies to cyclic citrullinated peptide in patients with early arthritis Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Low Frequency of Anticyclic Citrullinated Peptide Antibodies in Psoriatic Arthritis But Not in Cutaneous Psoriasis Comparative Performance Analysis of 4 Different Anti-Citrullinated Protein Assays in the Diagnosis of Rheumatoid Arthritis Diagnostic performances of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis Rheumatoid factors, anti-filaggrin antibodies and low in vitro interleukin-2 and interferon-gamma production are useful immunological markers for early diagnosis of community cases of rheumatoid arthritis. A preliminary study. Discovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ProteinChip approach. Anti-cyclic citrullinated peptide versus anti-Sa antibodies in diagnosis of rheumatoid arthritis in an outpatient clinic for connective tissue disease and spondyloarthritis. [Diagnostic utility of AxSYM anti-cyclic Citrullinated peptide antibody assay].
Our aim is to assess the prevalence and associated clinical features of  anti-CCP ( cyclic citrullinated peptide )  antibodies for RF ( rheumatoid factor)-positive and RF-negative rheumatoid arthritis ( RA ) and psoriatic arthritis ( PsA ) . In a prospect i ve , cross-sectional , multi-centre study , we determined the titres of anti-CCP antibodies in 208 RA patients ( 129 RF-positive , 79 RF-negative ) , 56 PsA patients and 39 healthy controls ( HC ) . Clinical parameters including disease activity ( disease activity score 28—DAS28 ) , physical disability ( health assessment question naire — HAQ ) , functional capacity ( functional class ) and radiological erosions were investigated in patients with RA . In PsA patients , clinical and radiological features were determined . Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay ( Euro-Diagnostica , Netherl and s ) . One-hundred four of 129 RF-positive RA ( 81 % ) , 16 of 79 RF-negative RA ( 20 % ) , seven of 56 PsA patients ( 12.5 % ) and none of the HC had anti-CCP antibodies . RA patients with anti-CCP antibodies had significantly higher disease activity , greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group . In subgroup analysis , anti-CCP antibodies in RF-negative patients were also associated with erosive disease . All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints . The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients . Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients . Both anti-CCP and RF tests were negative in 30 % of the patients . Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis Objective . Anti-cyclic citrullinated peptide ( anti-CCP ) antibodies are strongly associated with increased risk of rheumatoid arthritis (RA).While the anti-CCP level is commonly dichotomized for clinical use , the best threshold for and utility of the titer as a continuous variable to predict development of RA are uncertain . Methods . Using data from the Nurses ’ Health Study and Nurses ’ Health Study II longitudinal cohorts , we examined the sensitivity , specificity , and hazard of RA at various thresholds of the anti-CCP .  Incident RA was confirmed using the Connective Tissue Disease Screening Question naire and medical record review in 93 women from among 62,437 participants with blood sample s. Three controls per case were r and omly chosen , matching on cohort , age , and menopausal status . Stored plasma was tested for anti-CCP antibodies with the second-generation Diastat ™ ELISA . Five threshold values were assessed for sensitivity , specificity , and time to diagnosis of RA . Hazard of RA was assessed with conditional logistic regression models adjusting for smoking and reproductive factors . Results . Using the suggested threshold of > 5 U/ml for anti-CCP positivity , specificity was 100 % , but sensitivity was only 28 % . A threshold of > 2 U/ml had a higher sensitivity ( 51 % ) , and similar specificity ( 80 % ) , with an odds ratio of 11.2 ( 95 % confidence interval 4.7–26.9 ) for RA . Anti-CCP level as an ordinal variable was strongly associated with time to RA onset , with higher values predicting shorter time to RA onset . Conclusion . A lower threshold for anti-CCP positivity was more sensitive in predicting RA development . Higher ranges of the level were informative in predicting time to RA onset OBJECTIVE  Antiperinuclear factor ( APF ) ,  “ antikeratin antibodies ”  ( “ AKA ” ) , and antibodies to human epidermis filaggrin ( AFA ) , are highly specific serological markers of rheumatoid arthritis ( RA ) , which recognise epitopes on various isoforms of (pro)filaggrin . It was proposed that these antibodies are globally named antifilaggrin autoantibodies . Here the diagnostic value of the detection of each one is compared and the overlap between the three tests evaluated . METHODS 492 serum sample s were tested , including 279 RA serum sample s , taken from patients in France and Belgium .  APF and “ AKA ” titres were estimated by  indirect immunofluorescence  , and AFA titres by immunoblotting on filaggrin enriched human epidermis extracts . RESULTS By a convenient choice of the positivity thresholds , the diagnostic sensitivity and specificity of the tests were shown to be similar ( 0.52 and 0.97 , respectively ) . Although the antibody titres were strongly correlated , the associations APF-AFA or AFA-“AKA ” permitted more than 52 % or 55 % of RA to be diagnosed , with a specificity of 0.99 . CONCLUSION APF , “ AKA ” , and AFA detection have a similar diagnostic value . However , because the three tests do not totally overlap , associating APF with “ AKA ” or AFA with “ AKA ” can improve diagnostic sensitivity . None of the three antigens used bear all the epitopes recognised by anti-filaggrin autoantibodies Background : Early treatment prevents progression of joint damage in rheumatoid arthritis ( RA ) , but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria . Objective : To study the value of rheumatoid factor ( RF ) , anti-cyclic citrullinated peptide autoantibodies ( anti-CCP ) , and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis . Methods : The prospect i ve follow up inception cohort included 200 patients with very early ( <3 months ) inflammatory joint disease .  Autoantibodies  were measured at baseline and analysed in a tree based model which aim ed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone . Results : RA was diagnosed in 102 patients , while 98 developed other inflammatory arthropathies . Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml , above which anti-CCP and anti-RA33 had no additional diagnostic value . Remarkably , RF ⩾50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA , but overlapped considerably . Anti-RA33 was less specific and did not correlate with RF or anti-CCP . Among patients with RA , 72 % showed at least one of these three autoantibodies , compared with 15 % of non-RA patients . RF ⩾50 U/ml and anti-CCP were predictors of erosive disease , whereas anti-RA33 was associated with mild disease . Conclusions : Stepwise autoantibody testing in early inflammatory joint disease , starting with RF , followed by anti-CCP ( in patients with RF < 50 U/ml ) , and finally anti-RA33 , should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinical ly and followed prospect ively for 1 year to determine the clinical significance of a number of rheumatoid arthritis ( RA ) associated autoantibodies . Serum sample s collected at the time of the initial evaluation were tested for rheumatoid factor ( RF ) and antibodies to Sa ( anti-Sa ) , RA-33 , (pro)filaggrin [ antifilaggrin antibody ( AFA ) ] , cyclic citrullinated peptide ( anti-CCP ) , calpastatin , and keratin [ antikeratin antibody ( AKA ) ] . RF had a sensitivity of 66 % and a specificity of 87 % for RA . Anti-Sa , AFA , and anti-CCP all had a specificity of more than 90 % , but a sensitivity of less than 50 % for this diagnosis . Overall , there was a high degree of correlation between AFA , AKA , anti-Sa or anti-CCP , this being highest between anti-Sa and anti-CCP ( odds ratio , 13.3 ; P < 0.001 ) . Of the 101 patients who were positive for at least one of these four autoantibodies , 57 % were positive for only one . Finally , anti-SA identified a subset of predominantly male RA patients with  severe , erosive disease . Anti-SA , AFA and anti-CCP are all specific for early RA but , overall , have little additional diagnostic value over RF alone . Although these antibodies may preferentially recognize citrullinated antigens , the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses Rheumatoid factor ( RF ) is currently the most accepted laboratory test for rheumatoid arthritis ( RA ) and is part of the revised American College of Rheumatology ( ACR ) classification criteria for RA ( 1 ) . The specificity of RF is , however , often low (2)(3)(4)(5 ) . A newer diagnostic marker for RA is anti-citrullinated peptide antibodies ( ACPAs ) , which can be identified by tests such as a line immunoassay ( LIA ™ ) for the detection of anti-pepA and anti-pepB antibodies ( 6 ) , the anti-cyclic citrullinated peptide ELISA ( 7 ) , an ELISA using citrullinated recombinant rat filaggrin ( 8) , and an ELISA using deiminated fibrinogen ( 9 ) . ACPAs have excellent specificity ( 89–100 % ) for RA , with good sensitivity ( 41–80 % ) (3)(4)(5)(6)(7)(10)(11)(12)(13)(14)(15 ) . Furthermore , the HLA shared epitope ( SE ) has been described , which is found more often in RA patients than in controls (16)(17)(18 ) . Most studies of these newer tests have used control population s consisting of selected groups of patients with defined diseases and healthy controls . This does not represent real-life clinical practice because the composition of the control group does not reflect the natural prevalences of diseases in cases for which serologic markers for RA are requested . Data about specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) are thus hard to interpret . We design ed the present study to reflect everyday rheumatology practice . In this prospect i ve study , we included 1003 consecutive patients in three academic and nonacademic centers : the Department of Rheumatology , Ghent University Hospital ( Ghent , Belgium ) ; the Locomotor Center , Elisabeth Hospital ( Sijsele , Belgium ) ; and the Department of Rheumatology , St-Augustinus Hospital ( Wilrijk , Belgium ) . Patients were entered in the study when they presented with a new diagnostic problem for which RA was included in the differential diagnosis . This Anti-cyclic citrullinated peptide ( anti-CCP ) antibodies are used as highly specific and sensitive markers in the diagnosis of rheumatoid arthritis ( RA ) , in recent years . The aim of this prospect i ve and cross-sectional study was to measure the levels of anti-CCP and rheumatoid factor ( RF ) in patients with RA and osteoarthritis , and healthy volunteers to evaluate the specificity and possible diagnostic value of anti-CCP and RF , as well as their correlations with parameters of disease activity . Thirty-four patients with RA ( mean age : 53.8 + /- 8.6 ; 29 female ) , 32 patients with osteoarthritis ( mean age : 53.1 + /- 8.1 ; 26 female ) and 32 healthy controls ( mean age : 49.6 + /- 6.7 ; 24 female ) were evaluated between July 2004-July 2005 . RA diagnosis was done on the basis of criteria recommended by American College of Rheumatology ( ACR ) . Clinical parameters , including disease activity score ( DAS28 ) and health assessment question naire ( HAQ ) indices for physical capacity were detected for RA patients . As a result , 25 ( 73.5 % ) of the patients with RA were found positive for anti-CCP ( mean value : 74.6 + /- 64.9 RU/ml ) , while 24 ( 70.6 % ) were positive for RF ( mean value : 62.6 + /- 84.8 IU/ml ) . Serum levels of anti-CCP and RF showed statistically significant increase in patients with RA in comparison with osteoarthritis patients ( all were negative for anti-CCP ; 6.2 % were positive for RF ) and healthy controls ( all were negative for anti-CCP anf RF ) ( p < 0.001 ) . Twenty-two of the RA patients ( 64.7 % ) yielded positive results for both anti-CCP and RF , while seven ( 20.6 % ) were negative for both of the parameters . The sensitivity and specificity of anti-CCP reactivity for RA patients diagnosed based on ACR criteria were detected as 73.5 % and 100 % , respectively ; the corresponding results for RF were 70.6 % sensitivity and 96.8 % specificity . The mean DAS28 and HAQ scores of RA patients with anti-CCP and RF were higher than the patients without anti-CCP and RF , however these differences were not statistically significant ( p > 0.05 ) . Furthermore , a correlation between serum anti-CCP levels and HAQ score was determined , while there was no correlation between DAS28 and anti-CCP levels . In conclusion , antibodies against CCP were thought to be more specific than RF for RA , and the determination of anti-CCP in addition to RF could be helpful in serological diagnosis and monitorization of patients with RA OBJECTIVE To explore prospect ively the value of synovial histopathology in comparison with the value of classic parameters for diagnostic classification of spondylarthropathy ( SpA ) and rheumatoid arthritis ( RA ) in patients with an atypical disease presentation . METHODS  Synovial biopsy sample s were obtained from 154 consecutive patients presenting for diagnostic evaluation ; 67 patients fulfilled the classification criteria for RA , SpA , or other well-defined disease at the time of arthroscopy ( cohort 1 ) , and an additional 53 patients were classified after a full diagnostic reevaluation  at 6 months ( cohort 2 ) .  Synovial parameters with diagnostic value were identified in cohort 1 and were compared prospect ively with classic diagnostic parameters in cohort 2 . RESULTS Staining with anticitrulline , staining with monoclonal antibody 12A ( recognizing HLA-DR shared epitope-human cartilage glycoprotein 39(263 - 275 ) complexes ) , and crystal deposition had positive predictive values ( PPVs ) for diagnosis of > 90 % in patients with an atypical disease presentation ( cohort 2 ) . Using these 3 parameters , a diagnosis was predicted by  synovial histopathology  in 39.6 % of cohort 2 patients and turned out to be correct in 90.5 % of these patients at 6 months of followup . Using a multiparameter model rather than single histopathologic parameters , even better results were obtained , with a diagnostic prediction in 79.2 % of sample s and a PPV of 81.0 % . In comparison , a similar multiparameter model using classic diagnostic criteria rather than synovial histopathology performed poorly in cohort 2 ; the sensitivity was 56.6 % and the PPV was 73.3 % , with an inferior capacity to predict SpA. Especially for the presence of crystals and anticitrulline staining , the analysis of synovial tissue had a clear added value to the analysis of synovial fluid or serum in patients with an atypical presentation . CONCLUSION This proof-of-concept study indicates that synovial histopathology can contribute to the multiparametric diagnostic classification of inflammatory arthritis in patients with an atypical presentation Introduction Antibodies against cyclic citrullinated peptides ( CCPs ) are useful for diagnosing rheumatoid arthritis ( RA ) . Antibodies to mutated citrullinated vimentin ( MCV ) were described recently in RA . The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA . Methods We studied two groups of RA patients , one with ( n = 80 ) and one without ( n = 76 ) anti-CCP antibodies . The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases ( 51 psoriatic rheumatism , 58 primary Sjögren syndrome , and 49 ankylosis spondylitis ) .  Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6 , 12 , 18 , and 24 months of infliximab treatment .  Anti-CCP2 and anti-MCV levels  were assayed using a commercial enzyme-linked immunosorbent assay .  IgM rheumatoid factor was determined by nephelometry . Results In accordance with the cutoff values recommended by the manufacturer , the specificity of anti-MCV antibodies was 90.9 % . We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies ( 94.2 % ) . With this optimal cutoff , anti-MCV antibodies were found in 11.8 % ( 9/76 ) of RA patients without anti-CCP , and similarly , anti-CCP antibodies were found in 11.2 % ( 9/80 ) of RA patients without anti-MCV . Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor . Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline ( P < 0.01 ) as a significant decrease of anti-CCP levels occurred only at 24 months ( P < 0.04 ) . Moreover , an anti-MCV decrease was significantly associated with DAS28 ( disease activity score using 28 joint counts ) improvements 12 months into therapy . Conclusions Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV . Moreover , anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy OBJECTIVE To evaluate whether magnetic resonance imaging ( MRI ) of the wrists and finger joints and an analysis of serologic autoantibodies are clinical ly meaningful for the subsequent development of rheumatoid arthritis ( RA ) in patients with undifferentiated arthritis ( UA ) . METHODS A total of 129 patients with UA , a disease status formally confirmed by a rheumatologist over a period of at least 1 year , were included .  Gadolinium-diethylenetriamine-enhanced MRI of both wrists and finger joints and serologic variables were examined upon admission to our Early Arthritis Clinic at Nagasaki University . After a prospect i ve followup of 1 year , a predictive value for the development of RA was determined for each patient . RESULTS The subjects were evaluated for their positive or negative status with respect to 3 objective measures at study entry : anti-cyclic citrullinated peptide ( anti-CCP ) antibodies and /or IgM-rheumatoid factor , MRI-proven symmetric synovitis , and MRI-proven bone edema and /or bone erosion . The patients who were positive for at least 2 of these measures progressed to RA at 1 year with a 79.7 % positive predictive value ( PPV ) , 63.0 % negative predictive value , 75.9 % specificity , 68.0 % sensitivity , and 71.3 % accuracy . Furthermore , in 22 UA patients positive for both anti-CCP antibodies and MRI-proven bone edema who were considered to have progressed to RA at 1 year , the PPV was increased to 100 % . A close correlation was found between the present rule and that established in the Leiden Early Arthritis Cohort . CONCLUSION MRI-proven early joint damage in conjunction with serologic autoantibodies is efficient in predicting progression from UA to RA . This method can be used to identify patients who would benefit from early treatment with disease-modifying antirheumatic drugs OBJECTIVE The diagnosis of rheumatoid arthritis ( RA ) is sometimes difficult to establish early in the disease process , particularly in the absence of its classic hallmarks . Our aim was to compare the practical usefulness of magnetic resonance imaging ( MRI ) of the h and versus anticyclic citrullinated peptide ( anti-CCP ) antibody testing to confirm the diagnosis of clinical ly suspected RA in the absence of rheumatoid factor ( RF ) and radiographic erosions . METHODS We prospect ively included patients with early inflammatory arthritis and strong clinical suspicion of RA , in whom initial complementary tests ( RF and radiographs of h and s , wrists , and feet ) did not provide unequivocal confirmation of the diagnosis . In all patients , anti-CCP antibodies were assessed and contrast-enhanced MRI of the most affected h and was performed according to a specifically design ed protocol . The MRI criterion for the diagnosis of RA was either the presence of synovitis with bone erosions or bone marrow edema , which is currently considered to be a forerunner of erosions . RESULTS In the 40 patients ( 28 women ) , the mean age at diagnosis was 54 + /- 6 years and the median duration of symptoms was 4 + /- 2.6 months ( range 1.5 to 12 ) . Final diagnoses at 1-year follow-up were RA in 31 patients , undifferentiated arthritis in 7 ( 5 self-limiting ) , and psoriatic arthropathy ( PsA ) and antisynthetase syndrome in 1 patient each . Anti-CCP antibodies were positive only in 7 patients , all of whom were finally diagnosed with RA . The prevalence of anti-CCP positivity in our series of seronegative RA patients was thus 23 % ( 7/31 ) ; in these patients the anti-CCP antibodies had a specificity of 100 % ( 95 % CI : 71.7 to 100 ) and sensitivity of 23 % ( 95 % CI : 9.6 to 41.1 ) . Use of the MRI criterion led to the correct diagnosis in 100 % of patients with RA and to false-positive results ( 1 with PsA and 1 with antisynthetase syndrome ) . The MRI criterion had a specificity of 78 % ( 95 % CI : 40.0 to 97.2 ) and sensitivity of 100 % ( 95 % CI : 90.8 to 100 ) for identification of seronegative RA . CONCLUSION Although the tests are not mutually exclusive , in our experience MRI is more helpful than anti-CCP antibody determination in confirming the diagnosis of clinical ly suspected early RA in patients in whom the diagnosis can not be confirmed using conventional methods Antibodies directed against citrullinated vimentin are members of the family of autoantibodies reactive with citrullinated proteins and are among the most specific serological markers for the diagnosis of rheumatoid arthritis ( RA ) . This study was performed to test the diagnostic value of a newly developed enzyme-linked immunosorbent assay ( ELISA ) for the detection of antibodies against a genetically modified citrullinated vimentin ( anti-MCV ) in comparison with a second-generation anti-cyclic citrullinated peptides ( anti-CCP2 ) ELISA test system . Blinded sera from 631 patients ( 409 consecutive out- patients and 222 r and omly selected stored sera ) with RA ( n = 164 ) and non-RA ( osteoarthritis [ n = 120 ] , polymyalgia rheumatica/giant cell arteritis [ n = 80 ] , spondyloarthritis [ n = 36 ] , and other inflammatory rheumatic or non-inflammatory disease [ n = 67 ] ) were tested for the presence of anti-MCV and anti-CCP2 antibodies according to the manufacturers ' instructions . The diagnostic performance of the anti-MCV was comparable with the anti-CCP2 assay for the diagnosis of RA according to the calculated area under the curve ( 0.824 ; 95 % confidence interval ( CI ) 0.778–0.870 versus 0.818 ; 95 % CI 0.767–0.869 ) as analysed by receiving operating characteristic curve . When categorised with a cutoff value of 20.0 U/ml ( as recommended by the manufacturer ) , sensitivity and specificity of the anti-MCV ELISA were 69.5 % ( 95 % CI 61.9%–76.5 % ) and 90.8 % ( 86.9%–93.8 % ) , respectively , compared with 70.1 % ( 62.5%–77.0 % ) and 98.7 % ( 96.7%–99.6 % ) of the anti-CCP2 assay . Using the cutoff values of 19.0 U/ml and 81.5 U/ml for the anti-MCV test to obtain a sensitivity and specificity identical to the anti-CCP2 assay , showed a reduced specificity ( 89.8 % ; 85.8%–92.9 % ) and sensitivity ( 53.7 % ; 45.7%–61.5 % ) , respectively , of the anti-MCV ELISA compared with the anti-CCP2 test . In conclusion , the serum ELISA testing for anti-MCV antibodies as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA .  In the high-specificity range , however , the anti-CCP2 assay appears to be superior to the anti-MCV test The objective of this study was to determine the diagnostic value for rheumatoid arthritis ( RA ) of antibodies to cyclic citrullinated peptides ( anti-CCP ) in patients with early arthritis and vasculitis . Sixty-four adult patients with early arthritis and disease duration of less than 4 months were clinical ly diagnosed by an experienced rheumatologist as having RA ( n=27 ) , spondyloarthropathy ( n=11 ) , and undifferentiated arthritis ( n=26 ) . Eighteen patients with vasculitis were also included in the study . The patients with early arthritis were followed up for 9 months . After the follow-up period , five of 26 patients with undifferentiated arthritis were diagnosed as having RA . All serum sample s were tested for anti-CCP and IgM rheumatoid factor ( IgM-RF ) . The anti-CCP positivity in RA patients ( 44.4 % ) was significantly more frequent than in patients with undifferentiated arthritis ( 3.8 % ) , spondyloarthropathy ( 0 % ) , and vasculitis ( 5.6 % ) ( p=0.001 , p<0.01 , and p<0.01 , respectively ) . The frequency of IgM-RF positivity was 40.7 % in RA , 7.7 % in undifferentiated arthritis , 0 % in spondyloarthropathy , and 22.2 % in vasculitis groups . The respective specificity of anti-CCP and IgM-RF tests for early RA were 97.3 and 94.6 % , and the respective sensitivity of them were 44.4 and 40.7 % , respectively . The combination of anti-CCP and IgM-RF positivity had a very high specificity and positive predictive value ( 100 % ) but a rather low sensitivity ( 33.3 % ) . When either anti-CCP or IgM-RF positivity combined into one criterion , the sensitivity became high ( 51.9 % ) but the specificity decreased to 91.9 % . Overall performance of anti-CCP test alone for the early RA was higher than IgM-RF and the combination of anti-CCP and IgM-RF ( p<0.05 ) , and was similar to the combination of anti-CCP or IgM-RF . The specificity of positive anti-CCP test for diagnosis of established RA reached up to 100 % . In conclusion , the anti-CCP test is a new diagnostic test with extremely high specificity for RA . Anti-CCP antibody testing combined with IgM-RF testing has additional value over IgM-RF testing alone in patients with early arthritis OBJECTIVE To evaluate the prevalence and predictive value of  anti-cyclic citrullinated peptide ( anti-CCP ) antibodies  in individuals who subsequently developed rheumatoid arthritis ( RA ) and to determine the relationship to rheumatoid factor ( RF ) of any isotype . METHODS A case-control study was nested within the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden . Patients with RA were identified among blood donors whose sample s had been taken years before the onset of symptoms . Control subjects matched for age , sex , date of sampling , and residential area were selected r and omly from the same cohorts . Anti-CCP antibody and RFs were determined using enzyme immunoassays . RESULTS Eighty-three individuals with RA were identified as having donated blood before presenting with any symptoms of joint disease  ( median 2.5 years [ interquartile range 1.1 - 4.7 ] before RA ) . In sample s obtained before the onset of RA , the prevalence of autoantibodies was 33.7 % for anti-CCP , 16.9 % for IgG-RF , 19.3 % for IgM-RF , and 33.7 % for IgA-RF ( all highly significant compared with controls ) . The sensitivities for detecting these autoantibodies > 1.5 years and < /=1.5 years before the appearance of any RA symptoms were 25 % and 52 % for anti-CCP , 15 % and 30 % for IgM-RF , 12 % and 27 % for IgG-RF , and 29 % and 39 % for IgA-RF . In conditional logistic regression models , anti-CCP antibody and IgA-RF were found to be significant predictors of RA . CONCLUSION Anti-CCP antibody and RFs of all isotypes pre date d the onset of RA by several years . The presence of anti-CCP and IgA-RF predicted the development of RA , with anti-CCP antibody having the highest predictive value . This indicates that citrullination and the production of anti-CCP and RF autoantibodies are early processes in RA Background : Anticyclic citrullinated peptide ( anti-CCP ) antibodies are highly specific for the diagnosis of rheumatoid arthritis ( RA ) . The clinical distinction between RA and psoriatic arthritis ( PsA ) is often difficult to establish ; therefore , the presence of rheumatoid factor ( RF ) and anti-CCP antibodies could be useful . Seven percent to 40 % of patients with longst and ing psoriasis will develop PsA at some point . Therefore , it is important to study the positivity of these antibodies in these two interrelated population s. Objective : The aim of this study was to determine the seropositivity of anti-CCP antibodies in patients with psoriasis and PsA and to compare it with that seen in patients with other inflammatory , noninflammatory ( osteoarthritis ) arthritides and healthy controls . Patients and Methods : Serum anti-CCP antibodies  were measured in 106 patients with cutaneous psoriasis , 72 patients with PsA , 41 healthy controls ( HC ) , 41 patients with undifferentiated or early inflammatory arthritis ( UA ) , and 41 patients with RA and 41 with osteoarthritis using a commercial second-generation enzyme-linked immunosorbent assay . We considered a positive result to be > 20 UI/mL , as recommended by the manufacturer . Results : Of 106 patients with PsA , 55 were women and 51 men . The mean age was 42.87 ± 17.71 years and the mean disease duration was 5.3 ± 2.10 years  . Anti-CCP antibodies were not present in patients with psoriasis without arthritis . In contrast , 7 of 72 ( 9.72 % ) patients with PsA were positive for anti-CCP antibodies with a median titer of 7.16 units . Only one patient with PsA was positive for RF . Most of these patients were female with polyarticular joint involvement  . Distal interphalangeal involvement was present in 4 and 2 had dactylitis . We found clear differences when we compared patients with PsA with patients with psoriasis ( P = 0.001 ) . Of the 43 patients with UA studies , 4 initially exhibited a low titer positive anti-CCP antibody , and at follow up , another patient developed anti-CCP antibodies and later developed RA . None of the patients with UA developed PsA at 5-year follow up . Thirty-two of the 41 patients had a positive anti-CCP antibody and the mean ± st and ard deviation of the anti-CCP units was 80.61 ± 55.5.2 . Six of the 41 ( 14.6 % ) patients with osteoarthritis studied had positive anti-CCP with a mean titer of 7.388 . None of the healthy controls exhibited positively for anti-CCP antibodies . Conclusion : Anti-CCP antibodies may be found in patients with PsA and not in our patients with only cutaneous psoriasis . These antibodies may also be found in some patients with osteoarthritis and rarely in patients with UA ; such patients will be of interest to follow prospect ively Objective . To evaluate the diagnostic performances of 2 recently developed assays , third-generation anti-cyclic citrullinated peptide ( anti-CCP3 ) and anti-mutated citrullinated vimentin ( anti-MCV ) , in comparison to conventional second-generation anti-cyclic citrullinated peptide ( anti-CCP2 ) assay ; and to assess a novel fully automated , r and om-access AxSYM anti-CCP assay for early diagnosis of rheumatoid arthritis ( RA ) . Methods . A cohort of 176 patients was enrolled in our study ; 93 were diagnosed as having RA . The non-RA group consisted of 83 patients including 38 with systemic lupus erythematosus , 17 with primary Sjögren ’s syndrome , 11 with osteoarthritis , and 17 healthy controls . All were tested for presence of anti-CCP2 , anti-CCP3 , AxSYM anti-CCP , anti-MCV , and rheumatoid factor (RF)-IgM according to the manufacturers ’ instructions . Results . Diagnostic performance of the assays revealed the highest area under the curve for the novel AxSYM anti-CCP [ 89.1 ; 95 % confidence interval ( CI ) 84.3–93.8 ] , followed by anti-CCP3 ( 86.7 ; 95 % CI 81.6–91.9 ) , anti-CCP2 ( 82 ; 95 % CI 75.8–88.3 ) , and anti-MCV ( 71.9 ; 95 % CI 64.4–79.5 ) . The sensitivities and specificities were 60.2 % and 98.8 % for anti-CCP2 , 61.3 % and 97.6 % for anti-CCP3 , 80.6 % and 84.3 % for AxSYM anti-CCP , 49.8 % and 91.6 % for anti-MCV , and 67.8 % and 91.6 % for RF-IgM , respectively . Conclusion . At cutoff of 5 U/ml , AxSYM anti-CCP emerged as a highly sensitive first-line early diagnostic tool for RA , with the greatest discrimination power , above 16 U/ml , in case of positive result . Using a single easily performed automated assay at 2 determined decision limits we were able to diagnose 81 % of cases of RA and missing only 1.2 % To evaluate the rheumatoid arthritis ( RA ) diagnostic performances of anti-cyclic citrullinated peptide antibodies ( anti-CCP ) . Anti-CCP was detected by an enzyme linked immunosorbent assay in 164 patients with RA and 343 controls . In addition , anti-CCP predictive value for radiological damage were investigated in 37 recent-onset RA patients followed up prospect ively for 2 years .  Radiological damages were assessed by Sharp method modified by van der Heijde . The sensitivity of anti-CCP was 78.7 % and the specificity was 95.6 % . The positive predictive value and the negative predictive value were 90.2 % and 90.3 % , respectively . Anti-CCP were detected in sera of 79.3 % of patients with recent onset RA and 78.3 % of patients with long disease duration . In univariate and multivariate analyses , anti-CCP were not predictive for radiological damage . Our study confirms the high diagnostic performances of anti-CCP in RA . They are very useful to aid the diagnostic of RA in clinical practice OBJECTIVE To determine whether measurements of different  autoantibodies ( Ab ) and cytokines  are useful to distinguish very early rheumatoid arthritis ( RA ) from other inflammatory rheumatisms . METHODS From a population -based recruitment , 32 patients with very early polyarthritis ( median duration : 4 months ) were studied . Evaluations at entry ( M0 ) , and at 6 ( M6 ) and 12 months ( M12 ) . Ab tested : rheumatoid factors ( RF ) by agglutination methods and ELISA , antiperinuclear factor ( APF ) , antikeratin Ab  ( AKA ) , anti-Sa and antinuclear Ab . Cytokine production ( TNFalpha , IL2 , IFNgamma , IL1beta , IL10 ) in whole blood cell culture ( WBCC ) was determined at M0 . At M12 , patients were classified as having RA ( N = 15 ) or other rheumatic diseases . RESULTS At M0 , AKA/APF and anti-Sa Ab frequencies were low , 13 % and 7 % , respectively . While most Ab detected at M0 persisted , others appeared during follow-up , particularly APF , which rose from 13 to 40 % at M12 . At M6 , IgM-RF was detected in two RA patients exclusively by ELISA . AKA/APF were found to be highly specific markers for RA ( 100 % specificity ) . At some time during follow-up , two RF-negative RA patients were AKA-positive . In two patients , AKA and APF were present at M0 before they satisfied ACR criteria . IL2 and IFNgamma production was significantly lower ( P < 0.05 ) for RA patients . CONCLUSION AKA/APF and anti-Sa Ab were detected in community cases of very early RA . AKA/APF and RF detected by ELISA might contribute to an earlier diagnosis of RA . Low production of IFNgamma and IL2 in WBCC constituted a distinct immunopathological feature in very early RA patients OBJECTIVE To identify serum protein biomarkers specific for rheumatoid arthritis ( RA ) , using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ( SELDI-TOF-MS ) technology . METHODS A total of 103 serum sample s from patients and healthy controls were analyzed . Thirty-four of the patients had a diagnosis of RA , based on the American College of Rheumatology criteria . The inflammation control group comprised 20 patients with psoriatic arthritis ( PsA ) , 9 with asthma , and 10 with Crohn 's disease . The noninflammation control group comprised 14 patients with knee osteoarthritis and 16 healthy control subjects .  Serum protein profiles were obtained by SELDI-TOF-MS and compared in order to identify new biomarkers specific for RA . Data were analyzed by a machine learning algorithm called decision tree boosting , according to different preprocessing steps . RESULTS The most discriminative mass/charge ( m/z ) values serving as potential biomarkers for RA were identified on arrays for both patients with RA versus controls and patients with RA versus patients with PsA. From among several c and i date s , the following peaks were highlighted : m/z values of 2,924 ( RA versus controls on H4 arrays ) , 10,832 and 11,632 ( RA versus controls on CM10 arrays ) , 4,824 ( RA versus PsA on H4 arrays ) , and 4,666 ( RA versus PsA on CM10 arrays ) . Positive results of proteomic analysis were associated with positive results of the anti-cyclic citrullinated peptide test . Our observations suggested that the 10,832 peak could represent myeloid-related protein 8 . CONCLUSION SELDI-TOF-MS technology allows rapid analysis of many serum sample s , and use of decision tree boosting analysis as the main statistical method allowed us to propose a pattern of protein peaks specific for RA OBJECTIVE . To compare the diagnostic value of anti-cyclic citrullinated peptide ( anti-CCP ) and anti-Sa antibodies in serum for prediction of rheumatoid arthritis ( RA ) in an outpatient clinic for connective tissue diseases and spondyloarthritides . METHODS A cross-sectional study was carried out to analyze the presence or absence of anti-CCP and anti-Sa antibodies in the sera of 250 r and omly selected patients . The disease distribution in the study was as follows : 87 patients had RA ( 34.8 % ) ; 90 ( 36 % ) had other connective tissue diseases ( CTD ) ; 50 ( 20 % ) spondyloarthritis ; 19 ( 7.6 % ) polymyalgia rheumatica ; and 4 ( 1.6 % ) juvenile idiopathic arthritis . RESULTS  Anti-CCP antibodies  were detected in 63 patients with RA and in 9 patients with other illnesses [ sensitivity 72.4 % , specificity 94.4 % , positive predictive value ( PPV ) 87.5 % ] . Anti-Sa antibodies were detected in 38 patients with RA and in 6 patients with other illnesses ( sensitivity 43.6 % , specificity 96.3 % , PPV 86.3 % ) . Anti-CCP and anti-Sa results were discordant in up to 47 of 87 RA patients . No relation between the presence of anti-Sa and higher or lower titers of anti-CCP antibodies was observed . CONCLUSION The diagnostic value in RA is similar for both antibodies . However , the sensitivity of anti-CCP detection is higher than that of anti-Sa . Our results suggest that presence of anti-Sa antibodies in serum may be useful as a complementary assay when anti-CCP antibodies are negative and RA is suspected BACKGROUND The presence of rheumatoid factor ( RF ) is one of the classification criteria of the American College of Rheumatology ( ACR ) for rheumatoid arthritis ( RA ) , but it has a limitation of low specificity . We compared the diagnostic utility of anti-cyclic citrullinated peptide ( CCP ) antibodies analyzed by an automated immunoassay system with that measured by a 96 well plate ELISA method . METHODS The RF and anti-CCP antibodies were determined in 172 serum sample s : 52 RA patients , 73 disease controls ( systemic lupus , Sjogren 's syndrome , palindromic rheumatism ) , and 47 healthy controls .  Anti-CCP antibodies were measured by DIASTAT 96 well plate ELISA method ( Axis-Shield Diagnostics , UK ) and AxSYM automated microparticle enzyme immunoassay system ( Abbott Laboratories , USA ) . RF was assayed by latex immunoturbidimetry ( Toshiba 200 FR , Japan ) . The diagnostic performances of these tests were compared using a ROC curve analysis , and linearity and precision analysis of AxSYM anti-CCP was carried out . RESULTS The sensitivities of RF , DIASTAT anti-CCP , and AxSYM anti-CCP were 78.8 % , 84.6 % , and 82.7 % , respectively and the specificities were 72.5 % , 88.3 % , and 88.3 % , respectively . On ROC curve analysis , the area under the curve was 0.924 for AxSYM anti-CCP , 0.886 for DIASTAT anti-CCP , and 0.847 for RF . AxSYM anti-CCP showed a good linearity , and within-run and total-run precision . CONCLUSIONS Diagnostic performance of automated AxSYM anti-CCP assay was comparable to that of DIASTAT 96 well plate ELISA method . AxSYM anti-CCP assay has an advantage of r and om access capability and will be useful in laboratories with low sample number and /or with a need of rapid turnaround time
BACKGROUND Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage .
Anti-citrullinated peptide antibodies ( ACPA ) have been suggested for early diagnosis .
PURPOSE To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease .