human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    