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\251 2004. All rights reserved)Tj
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(DISCUSSION)Tj
/T1_2 1 Tf
0.1684 Tw 0 -1.2 TD
[(W)79.9 (e observed that anti-CCP)-381.7 (antibodies can be detected in)]TJ
0.0042 Tw T*
(patients with JIA, especially those patients with RF positive)Tj
0.0972 Tw T*
[(polyarthritis. In addition, we found anti-CCP)-310.5 (antibodies in)]TJ
0.01421 Tw T*
[(patients with SLE, albeit with lower specificity)64.8 (. Subsequent)]TJ
0.01019 Tw T*
(studies have shown a patient with psoriatic arthritis and one)Tj
0.0567 Tw T*
(with mixed connective tissue disease that were positive for)Tj
0.07201 Tw T*
[(anti-CCP)-285.2 (antibodies. )17.8 (These non-RA)-267.1 (disease groups did not)]TJ
0.0408 Tw T*
(have RA-like arthritis, supporting the observation that anti-)Tj
0.07291 Tw T*
[(CCP)-286.2 (are not RA-specific, but rather are highly sensitive in)]TJ
0.04739 Tw T*
[(RA)-242.6 (and JIA. Further)39.7 (, this study demonstrates that citrulline)]TJ
0.1167 Tw T*
(can be considered an antigenic determinant recognized by)Tj
0.02499 Tw T*
[(antibodies in JIA)-220.2 (sera, among other diseases.)]TJ
0.1635 Tw 1.2 -1.18 Td
[(W)79.9 (e also demonstrate that an ELISA)-358.7 (based test for the)]TJ
0.2834 Tw -1.2 -1.18 Td
[(presence of anti-CCP)-496.7 (antibodies in JIA)-478.6 (can be adapted)]TJ
0.2231 Tw 0 -1.18 TD
(utilizing both synthetic linear and cyclic peptides as the)Tj
0.3476 Tw T*
[(antigen. )17.7 (W)39.8 (ith predefined sequences, lar)17.7 (ge quantities of)]TJ
0.13989 Tw T*
(synthetic peptides can be produced with a high degree of)Tj
0.12669 Tw T*
[(purity)64.8 (. However)39.7 (, an innate problem exists with the use of)]TJ
0.02541 Tw T*
(relatively short \(linear\) peptides. Because they generally do)Tj
0.0256 Tw T*
(not adopt a stabilized conformation in solution, only a frac-)Tj
0.0639 Tw T*
(tion of the peptides adopt a form comparable to that of the)Tj
0.02049 Tw T*
[(original antigenic site on the complete protein antigen. )17.7 (This)]TJ
0.04221 Tw T*
[(results in a direct negative ef)17.7 (fect on the af)17.7 (finity of the anti-)]TJ
0.0199 Tc 0.4326 Tw T*
(body for the peptide, despite the peptide sequence)Tj
-0.00011 Tc -0.03709 Tw T*
(comprising the whole antigenic site, and the increased possi-)Tj
0.0132 Tw T*
(bility for nonspecific binding)Tj
-0.0567 Tc 0 Tw 6.5 0 0 6.5 160.3111 425.2618 Tm
(11)Tj
-0.00011 Tc 0.0132 Tw 10 0 0 10 166.4424 421.9618 Tm
[(. )17.7 (The findings with the linear)]TJ
0.12849 Tw -12.3442 -1.18 Td
(variants, cfc-318 and cfc-319, exemplify this principle, as)Tj
0.02229 Tw T*
(the corresponding rates of positive values were elevated for)Tj
0.20461 Tw T*
(the patients with RF negative polyarthritis, oligoarthritis,)Tj
0.355 Tw T*
[(and systemic arthritis JIA)-550.2 (and the SLE patients when)]TJ
0.0349 Tw T*
(compared to values utilizing both the cyclic variant and the)Tj
0.1368 Tw T*
[(kits. It is important to note that both the Inova and )54.8 (Axis-)]TJ
0.0564 Tw T*
(Shield kits use identical antigenic peptides provided by the)Tj
0.17841 Tw T*
[(same source. Previous Inova kits with dif)17.7 (ferent antigenic)]TJ
0.3741 Tw T*
(peptides gave data similar to those found with the 3)Tj
0.02499 Tw T*
(synthetic peptides.)Tj
0.1913 Tw 1.2 -1.18 Td
(The etiology of the antigenicity of citrulline has been)Tj
-0.0125 Tw -1.2 -1.18 Td
[(debated. In most cases ar)17.7 (ginine is modified to citrulline, and)]TJ
0.23489 Tw T*
(this modified antigen could possibly evoke a polyclonal)Tj
0.0027 Tc 0.37219 Tw T*
[(antibody response against citrulline. )17.6 (The antibodies to)]TJ
-0.00011 Tc 0.2756 Tw T*
[(citrulline in JIA)-470.9 (are similar to the percentages in adult)]TJ
0.0851 Tw T*
(patients with RA, the majority being RF positive)Tj
0 Tc 0 Tw 6.5 0 0 6.5 243.9284 236.462 Tm
[(7,1)56.7 (1)]TJ
-0.00011 Tc 0.0851 Tw 10 0 0 10 254.9347 233.162 Tm
(. Since)Tj
0.0537 Tw -21.1935 -1.18 Td
[(previous observations indicate that anti-CCP)-267 (antibodies are)]TJ
0.00031 Tc 0.3746 Tw T*
(most commonly found in patients with RA, it is not)Tj
-0.00011 Tc 0.1396 Tw T*
(surprising to find them in certain subsets of patients with)Tj
0.00281 Tc 0.3721 Tw T*
(JIA, especially patients with RF positive polyarthritis.)Tj
-0.00011 Tc 0.00591 Tw T*
[(However the presence of anti-CCP)-219.1 (antibodies did not corre-)]TJ
0.1577 Tw T*
(late directly with presence of RF as in adults)Tj
0 Tc 0 Tw 6.5 0 0 6.5 233.8835 165.6621 Tm
[(7,1)56.7 (1)]TJ
-0.00011 Tc 0.1577 Tw 10 0 0 10 244.8898 162.3621 Tm
[(. Further)39.7 (,)]TJ
0 Tw -20.189 -1.18 Td
[(A)73.9 (vcin, )]TJ
/T1_3 1 Tf
-0.02209 Tw 2.8475 0 Td
(et al)Tj
/T1_2 1 Tf
0 Tc 0 Tw 6.5 0 0 6.5 88.749 153.8621 Tm
(12)Tj
-0.00011 Tc -0.02209 Tw 10 0 0 10 97.5278 150.5621 Tm
[(detected anti-CCP)-191.1 (antibodies in 2% of patients)]TJ
0.1032 Tw -5.4528 -1.18 Td
(with JIA, which is much less common than in adults with)Tj
0.12781 Tw T*
[(RA. )17.7 (T)69.9 (wo limitations are noted that would account for the)]TJ
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[(discrepancy between the results of )54.8 (A)73.9 (vcin, )]TJ
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[-0.5 (et al)]TJ
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0 Tc 0 Tw 6.5 0 0 6.5 240.4264 118.4621 Tm
(12)Tj
-0.00011 Tc 0.16541 Tw 10 0 0 10 251.0801 115.1621 Tm
(and our)Tj
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[(study)64.8 (. First, their study included a small number of seropos-)]TJ
0.2402 Tw T*
[(itive polyarticular patients. )17.7 (W)79.9 (e hypothesize that a lar)17.7 (ger)]TJ
0.2886 Tw 26.4 63.9599 Td
(seropositive polyarticular cohort would reveal a signifi-)Tj
0.0325 Tw T*
[(cantly higher correlation with anti-CCP)-245.8 (antibodies. Further)39.7 (,)]TJ
0.17909 Tw T*
[(the patients in their group were from a lar)17.7 (ge multicenter)]TJ
-0.033 Tw T*
(study with no inclusion criteria other than their clinical diag-)Tj
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(nosis)Tj
0 Tc 6.5 0 0 6.5 327.5566 687.2617 Tm
(12)Tj
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[(. In addition, anti-CCP)-324.3 (antibody positivity in JIA)-306.2 (is)]TJ
0.03729 Tw -2.7057 -1.18 Td
[(transient over the course of the disease. )17.7 (Therefore, the time)]TJ
0.2944 Tw T*
(\(in relation to disease activity\) at which the sera were)Tj
0.03529 Tw T*
[(obtained would influence the anti-CCP)-248.5 (antibody concentra-)]TJ
0.23891 Tw T*
(tion. Previously in the separation of immune complexes)Tj
0.00909 Tw T*
[(from the sera of JIA)-204.3 (patients we had noted a 40 kDa band)]TJ
0 Tc 0 Tw 6.5 0 0 6.5 538 628.2618 Tm
(13)Tj
10 0 0 10 544.4999 624.9617 Tm
(.)Tj
-0.00011 Tc 0.0394 Tw -23.75 -1.18 Td
[(Isolation of immune complexes was by af)17.7 (finity chromatog-)]TJ
0.1792 Tw T*
[(raphy)64.8 (, sodium dodecyl sulfate gradient, and )17.8 (W)79.9 (estern blot)]TJ
0.1786 Tw T*
(analysis. Four bands were noted, a 70 kDa band of IgM)Tj
0.0703 Tw T*
(heavy chain, a 50 kDa band of IgG heavy chain, a 60 kDa)Tj
0.17979 Tw T*
(band, possibly a heat-shock protein, and a 40 kDa band,)Tj
0.05321 Tw T*
(which may be a cyclic citrullinated protein. Further studies)Tj
0.14 Tw T*
(may give more information on the antigenic determinants)Tj
0.02499 Tw T*
[(responsible for the production of anti-CCP)-238.3 (antibodies.)]TJ
0.0224 Tw 1.2 -1.2 Td
[(Our data indicate anti-CCP)-235.6 (antibodies can be detected in)]TJ
0.00639 Tw -1.2 -1.2 Td
[(sera from patients with JIA)-201.7 (and may indicate a possible role)]TJ
0.02499 Tw 0 -1.2 TD
(of citrulline-containing epitopes in the pathogenesis of JIA.)Tj
/T1_1 1 Tf
0 Tw 0 -2.4 TD
(REFERENCES)Tj
/T1_2 1 Tf
0.02499 Tw 8 0 0 8 314 460.5618 Tm
[(1.)-875.1 (Cassidy JT)73.9 (, Petty RE. Juvenile rheumatoid arthritis. In: Cassidy JT)73.9 (,)]TJ
1.675 -1.25 Td
[(Petty RE, editors. )17.7 (T)69.9 (extbook of pediatric rheumatology)64.8 (.)]TJ
0 -1.25 TD
[(Philadelphia: )17.7 (WB Saunders; 2001:218-322.)]TJ
-1.675 -1.25 Td
[(2.)-875.1 (Petty RE, Southwood )17.7 (TR, Baum J, et al. Revision of the proposed)]TJ
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(classification criteria for juvenile idiopathic arthritis: Durban 1997.)Tj
T*
(J Rheumatol 1998;25:1991-4.)Tj
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[(3.)-875.1 (Moore )17.7 (TL. Rheumatoid factors. Clin Immunol 1998;18:89-96.)]TJ
T*
[(4.)-875.1 (Moore )17.7 (TL, Dorner R)54.8 (W)91.8 (, Osborn )17.7 (TG, Zuckner J. Hidden 19 S IgM)]TJ
1.675 -1.25 Td
[(rheumatoid factors. Semin )54.8 (Arthritis Rheum 1988;18:72-5.)]TJ
-1.675 -1.25 Td
[(5.)-875.1 (Nienhaus RLF)79.7 (, Mandema E. )54.8 (A)-220.1 (new serum factor in patients with)]TJ
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[(rheumatoid arthritis \321 the antiperinuclear factor)54.8 (. )54.8 (Ann Rheum Dis)]TJ
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(1964;23:302-5.)Tj
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[(6.)-875.1 (Nesher G, Moore )17.7 (TL, Grisanti MW)91.7 (, El-Najdawi E, Osborn )17.7 (TG.)]TJ
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[(Antiperinuclear factor in juvenile rheumatoid arthritis. )54.8 (Ann Rheum)]TJ
T*
(Dis 1992;51:350-2.)Tj
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[(7.)-875.1 (Schellekens GA, de Jong BA)79.7 (W)91.8 (,)-0.1 ( van den Hoogen FHJ, van de Putte)]TJ
1.675 -1.25 Td
[(LBA, van )17.7 (V)110.8 (enrooij )17.7 (WJ. Citrulline is an essential constituent of )]TJ
T*
(antigenic determinants recognized by rheumatoid arthritis-specific)Tj
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(autoantibodies. J Clin Invest 1998;101:273-81.)Tj
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[(8.)-875.1 (Hoet RM, Boerbooms )54.8 (AMT)73.9 (, )54.8 (Arends M, Ruiter DJ, van )17.7 (V)110.8 (enrooij)]TJ
1.675 -1.25 Td
[(WJ. )54.8 (Antiperinuclear factor)39.7 (, a marker autoantibody for rheumatoid)]TJ
T*
(arthritis: colocalization of the perinuclear factor and profilaggrin.)Tj
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[(Ann Rheum Dis 1991;50:61)36.9 (1-8.)]TJ
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[(9.)-875.1 (Sebbag M, Simon M, )17.7 (V)59.8 (incent C, et al. )17.7 (The antiperinuclear factor)]TJ
1.675 -1.25 Td
(and the so-called anti-keratin antibodies are the same rheumatoid)Tj
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(arthritis-specific autoantibodies. J Clin Invest 1995;95:2672-9.)Tj
-2.175 -1.25 Td
[(10.)-875.1 (Gan SQ, McBride OW)91.7 (, Idler )17.7 (WW)91.7 (, Nedialka M, Steinert PM.)]TJ
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[(Or)17.7 (ganization, structure, and polymorphisms of the human )]TJ
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(profilaggrin gene. Biochemistry 1990;29:9432-40.)Tj
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[(1)36.8 (1)-0.1 (.)-875.1 (Schellekens GA, )17.7 (V)59.8 (isser H, de Jong BA)79.7 (W)91.8 (, et al. )17.7 (The diagnostic)]TJ
2.1381 -1.25 Td
(properties of rheumatoid arthritis antibodies recognizing a cyclic)Tj
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[(citrullinated peptide. )54.8 (Arthritis Rheum 2000;43:155-63.)]TJ
-2.175 -1.25 Td
[(12.)-875.1 (A)74 (vcin )17.7 (T)74 (, Cimaz R, Falcini F)79.7 (, et al. Prevalence and clinical )]TJ
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(significance of anti-cyclic citrullinated peptide antibodies in )Tj
T*
[(juvenile idiopathic arthritis. )54.8 (Ann Rheum Dis 2002;61:608-1)36.8 (1.)]TJ
-2.175 -1.25 Td
[(13.)-875.1 (Moore )17.7 (TL, Osborn )17.7 (TG, Nesher G. Immune complexes from sera of)]TJ
2.175 -1.25 Td
(patients with juvenile rheumatoid arthritis reveal novel 40 and 60)Tj
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(kD bands. Clin Exp Rheumatol 1995;13:667-72.)Tj
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-0.00011 Tc 8 0 0 8 43.5 53.9844 Tm
[(Low)73.9 (, et al: )17.7 (Anti-CCP)-257.3 (and JIA)]TJ
0 Tc 0 Tw 60.9375 -0.0313 Td
(1833)Tj
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97.22 76.74 396.48 -10.83 re
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(Personal, non-commercial use only. The Journal of Rheumatology. Copyri\
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