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Cristina Regueiro, Ana M. Ortiz, Maria Dolores Boveda, Santos Castañeda, Isidoro Gonzalez-Alvaro, Antonio Gonzalez
Association of high titers of anti-carbamylated protein antibodies with decreased bone mineral density in early arthritis patients
www.plosone.org
www.plosone.org
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(Early)Tj
2.2961 0 Td
(Arthritis)Tj
3.668 0 Td
(Register)Tj
3.4526 0 Td
(Longitudinal)Tj
-28.6524 -1.2982 Td
(\(PEARL\))Tj
3.8721 0 Td
(study)Tj
2.3867 0 Td
(were)Tj
2.126 0 Td
(analyzed.)Tj
3.9231 0 Td
(This)Tj
1.9899 0 Td
(register)Tj
3.2031 0 Td
(includes)Tj
3.5433 0 Td
(patients)Tj
3.3676 0 Td
(submitted)Tj
4.2519 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(EA)Tj
1.474 0 Td
(clinic)Tj
2.3924 0 Td
(of)Tj
-35.0246 -1.3039 Td
(Hospital)Tj
3.6169 0 Td
(Universitario)Tj
5.5276 0 Td
(La)Tj
1.1905 0 Td
(Princesa)Tj
3.6113 0 Td
(\(Madrid;)Tj
3.8041 0 Td
(Spain\))Tj
2.8006 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(suspicion)Tj
3.9968 0 Td
(of)Tj
1.0148 0 Td
(arthritis)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(less)Tj
1.6101 0 Td
(than)Tj
2.0296 0 Td
(a)Tj
-36.3626 -1.2983 Td
(year)Tj
1.9048 0 Td
(of)Tj
1.0148 0 Td
(evolution.)Tj
4.2236 0 Td
(The)Tj
1.7802 0 Td
(register)Tj
3.2031 0 Td
(protocol)Tj
3.6 0 Td
(includes)Tj
3.5432 0 Td
(5)Tj
0.6974 0 Td
(standardized)Tj
5.3517 0 Td
(visits)Tj
2.2281 0 Td
(\(baseline,)Tj
3.9968 0 Td
(6,)Tj
0.9184 0 Td
(12,)Tj
1.4003 0 Td
(24)Tj
1.1679 0 Td
(and)Tj
-35.0303 -1.2983 Td
(60)Tj
1.1678 0 Td
(months\))Tj
3.6227 0 Td
(at)Tj
0.9524 0 Td
(which)Tj
2.6532 0 Td
(information)Tj
5.074 0 Td
(about)Tj
2.4945 0 Td
(demographics,)Tj
6.0888 0 Td
(clinical)Tj
3.0784 0 Td
(status,)Tj
2.7269 0 Td
(disability,)Tj
4.0762 0 Td
(laboratory)Tj
-31.9349 -1.2982 Td
(findings)Tj
3.4922 0 Td
(and)Tj
1.7291 0 Td
(treatment)Tj
4.1386 0 Td
(is)Tj
0.8447 0 Td
(collected.)Tj
3.9685 0 Td
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2.0182 0 Td
(composite)Tj
4.3484 0 Td
(measures)Tj
3.9401 0 Td
(of)Tj
1.0148 0 Td
(disease)Tj
3.016 0 Td
(activity)Tj
3.1181 0 Td
(were)Tj
2.1203 0 Td
(used,)Tj
2.2904 0 Td
(the)Tj
-36.0394 -1.3039 Td
(Disease)Tj
3.2258 0 Td
(Activity)Tj
3.3675 0 Td
(Score)Tj
2.4208 0 Td
(28)Tj
1.1735 0 Td
(\(DAS28\),)Tj
3.9685 0 Td
(which)Tj
2.6532 0 Td
(assesses)Tj
3.3052 0 Td
(the)Tj
1.4683 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(tender)Tj
2.8119 0 Td
(joints)Tj
2.4605 0 Td
(and)Tj
1.7291 0 Td
(swollen)Tj
-33.0177 -1.2983 Td
(joints)Tj
2.4547 0 Td
(\(28)Tj
1.5137 0 Td
(joints)Tj
2.4605 0 Td
(maximum\),)Tj
4.9379 0 Td
(erythrocyte)Tj
4.7735 0 Td
(sedimentation)Tj
5.9414 0 Td
(rate)Tj
1.7518 0 Td
(and)Tj
1.7291 0 Td
(global)Tj
2.6249 0 Td
(patient)Tj
3.0047 0 Td
(health)Tj
2.6816 0 Td
(status)Tj
-33.8738 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(];)Tj
2.0749 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.474 0 Td
(Hospital)Tj
3.617 0 Td
(Universitario)Tj
5.5275 0 Td
(La)Tj
1.1906 0 Td
(Princesa)Tj
3.6056 0 Td
(Index)Tj
2.5285 0 Td
(\(HUPI\),)Tj
3.5263 0 Td
(which)Tj
2.6532 0 Td
(includes)Tj
3.5433 0 Td
(the)Tj
1.4683 0 Td
(same)Tj
2.2621 0 Td
(vari-)Tj
-35.2004 -1.3039 Td
(ables)Tj
2.1826 0 Td
(but)Tj
1.5477 0 Td
(with)Tj
1.9843 0 Td
(a)Tj
0.6463 0 Td
(modified)Tj
3.8437 0 Td
(calculation)Tj
4.5694 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
2.0693 0 Td
(At)Tj
1.1906 0 Td
(each)Tj
2.0239 0 Td
(visit,)Tj
2.0863 0 Td
(biological)Tj
4.0818 0 Td
(samples)Tj
3.3732 0 Td
(are)Tj
1.44 0 Td
(taken,)Tj
2.6419 0 Td
(processed)Tj
-33.681 -1.2983 Td
(and)Tj
1.7291 0 Td
(frozen)Tj
2.7722 0 Td
(at)Tj
0.9525 0 Td
(-80C.)Tj
2.8006 0 Td
(A)Tj
0.9071 0 Td
(detailed)Tj
3.3675 0 Td
(description)Tj
4.7282 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(PEARL)Tj
3.1918 0 Td
(study)Tj
2.3867 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1259 0 Td
(previously)Tj
4.3483 0 Td
(published)Tj
-33.3408 -1.2982 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(].)Tj
2.0749 0 Td
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1.6271 0 Td
(this)Tj
1.6724 0 Td
(work,)Tj
2.5058 0 Td
(we)Tj
1.3266 0 Td
(used)Tj
2.058 0 Td
(exclusively)Tj
4.5184 0 Td
(information)Tj
5.0739 0 Td
(and)Tj
1.7292 0 Td
(serum)Tj
2.7269 0 Td
(samples)Tj
3.3789 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.474 0 Td
(baseline)Tj
3.4299 0 Td
(vis-)Tj
-35.8013 -1.3039 Td
(its)Tj
1.1451 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3676 0 Td
(recruited)Tj
3.8551 0 Td
(from)Tj
2.2053 0 Td
(February)Tj
3.8381 0 Td
(2002)Tj
2.1203 0 Td
(to)Tj
1.0261 0 Td
(April)Tj
2.3074 0 Td
(2017.)Tj
2.3471 0 Td
(All)Tj
1.3946 0 Td
(the)Tj
1.474 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
1.9955 0 Td
(relevant)Tj
3.4186 0 Td
(infor-)Tj
-34.8772 -1.2983 Td
(mation)Tj
3.0954 0 Td
(and)Tj
1.7291 0 Td
(serum)Tj
2.7212 0 Td
(were)Tj
2.126 0 Td
(included.)Tj
3.9345 0 Td
(However,)Tj
4.0762 0 Td
(patients)Tj
3.3675 0 Td
(were)Tj
2.126 0 Td
(classified)Tj
3.8154 0 Td
(as)Tj
1.0148 0 Td
(having)Tj
2.9196 0 Td
(RA)Tj
1.5251 0 Td
(according)Tj
4.1895 0 Td
(to)Tj
-36.6403 -1.2983 Td
(the)Tj
1.4683 0 Td
(2010)Tj
2.1203 0 Td
(ACR/EULAR)Tj
5.6692 0 Td
(classification)Tj
5.3462 0 Td
(criteria)Tj
3.0784 0 Td
(for)Tj
1.3833 0 Td
(specific)Tj
3.1917 0 Td
(analysis)Tj
3.3279 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(].)Tj
2.0749 0 Td
(All)Tj
1.4004 0 Td
(patients)Tj
3.3675 0 Td
(provided)Tj
-32.4281 -1.2982 Td
(their)Tj
2.1089 0 Td
(written)Tj
3.1068 0 Td
(informed)Tj
3.9741 0 Td
(consent)Tj
3.3335 0 Td
(to)Tj
1.0262 0 Td
(participate)Tj
4.4673 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(study.)Tj
2.6135 0 Td
(The)Tj
1.7858 0 Td
(PEARL)Tj
3.1918 0 Td
(study)Tj
2.3867 0 Td
(was)Tj
1.7008 0 Td
(approved)Tj
3.9742 0 Td
(by)Tj
-36.1755 -1.3039 Td
(the)Tj
1.4683 0 Td
(Research)Tj
3.8041 0 Td
(Ethics)Tj
2.6702 0 Td
(Committee)Tj
4.7395 0 Td
(of)Tj
1.0148 0 Td
(Hospital)Tj
3.617 0 Td
(Universitario)Tj
5.5275 0 Td
(La)Tj
1.1905 0 Td
(Princesa)Tj
3.6113 0 Td
(\(PI-518\).)Tj
3.7984 0 Td
(This)Tj
1.99 0 Td
(study)Tj
2.3867 0 Td
(was)Tj
-35.8183 -1.2983 Td
(approved)Tj
3.9741 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
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3.8098 0 Td
(Ethics)Tj
2.6645 0 Td
(Committee)Tj
4.7395 0 Td
(of)Tj
1.0148 0 Td
(Galicia)Tj
3.0104 0 Td
(\(Spain,)Tj
3.0274 0 Td
(code)Tj
2.0976 0 Td
(2014/387\).)Tj
4.4447 0 Td
(Both)Tj
2.1373 0 Td
(studies)Tj
-33.5676 -1.2983 Td
(were)Tj
2.1203 0 Td
(conducted)Tj
4.4276 0 Td
(according)Tj
4.1896 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(principles)Tj
4.1612 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(Declaration)Tj
4.9095 0 Td
(of)Tj
1.0148 0 Td
(Helsinki)Tj
3.6 0 Td
(\(2013\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 407.0551 cm
BT
/F13 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(ACPA)Tj
2.9008 0 Td
(detection)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 390.0472 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(ACPA)Tj
2.8119 0 Td
(were)Tj
2.1203 0 Td
(measured)Tj
4.1102 0 Td
(using)Tj
2.3868 0 Td
(a)Tj
0.6519 0 Td
(second-generation)Tj
7.6535 0 Td
(anti-citrullinated)Tj
6.9959 0 Td
(cyclic)Tj
2.4604 0 Td
(peptide)Tj
3.1918 0 Td
(enzyme)Tj
-32.3827 -1.2982 Td
(immunoassay)Tj
5.7542 0 Td
(\(EIA;)Tj
2.3755 0 Td
(Euro-Diagnostica)Tj
7.2906 0 Td
(Immunoscan)Tj
5.5502 0 Td
(RA;)Tj
1.7518 0 Td
(positive)Tj
/F14 1 Tf
0 Tc
(>)Tj
/F8 1 Tf
-0.004 Tc
(50)Tj
5.0343 0 Td
(U/ml\))Tj
2.6929 0 Td
(until)Tj
2.109 0 Td
(October)Tj
-32.5585 -1.3039 Td
(2010,)Tj
2.347 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.652 0 Td
(third-generation)Tj
6.8541 0 Td
(EIA)Tj
1.8142 0 Td
(\(QUANTA)Tj
4.7565 0 Td
(Lite)Tj
1.7461 0 Td
(CCP3)Tj
2.5795 0 Td
(IgG)Tj
1.7462 0 Td
(and)Tj
1.7291 0 Td
(IgA,)Tj
1.9332 0 Td
(Inova)Tj
2.5058 0 Td
(Diagnostics;)Tj
-30.3928 -1.2983 Td
(positive)Tj
/F14 1 Tf
0 Tc
(>)Tj
/F8 1 Tf
-0.004 Tc
(40)Tj
5.0399 0 Td
(U/ml\))Tj
2.6872 0 Td
(afterwards.)Tj
4.6432 0 Td
(Both)Tj
2.1316 0 Td
(methods)Tj
3.685 0 Td
(are)Tj
1.4457 0 Td
(EIA,)Tj
2.0409 0 Td
(but)Tj
1.5534 0 Td
(the)Tj
1.4683 0 Td
(third-generation)Tj
6.8485 0 Td
(assay)Tj
2.2677 0 Td
(is)Tj
0.8447 0 Td
(able)Tj
1.8312 0 Td
(to)Tj
-36.4873 -1.2983 Td
(detect)Tj
2.6135 0 Td
(IgA)Tj
1.7121 0 Td
(ACPA)Tj
2.8063 0 Td
(in)Tj
1.0374 0 Td
(addition)Tj
3.6 0 Td
(to)Tj
1.0205 0 Td
(IgG)Tj
1.7405 0 Td
(antibodies,)Tj
4.5864 0 Td
(with)Tj
2.0012 0 Td
(no)Tj
1.2756 0 Td
(other)Tj
2.3471 0 Td
(important)Tj
4.2803 0 Td
(differences)Tj
4.5637 0 Td
(between)Tj
-33.5846 -1.3039 Td
(these)Tj
2.2506 0 Td
(two)Tj
1.7122 0 Td
(techniques.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 294.9732 cm
BT
/F13 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Determination)Tj
6.4394 0 Td
(of)Tj
1.0677 0 Td
(anti-CarPA)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 278.022 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(We)Tj
1.61 0 Td
(used)Tj
2.058 0 Td
(FCS)Tj
1.8878 0 Td
(\(F-7524,)Tj
3.566 0 Td
(Sigma-Aldrich\))Tj
6.4176 0 Td
(as)Tj
1.0148 0 Td
(source)Tj
2.8346 0 Td
(of)Tj
1.0148 0 Td
(proteins)Tj
3.5149 0 Td
(for)Tj
1.3833 0 Td
(testing)Tj
2.8857 0 Td
(anti-CarP)Tj
4.1442 0 Td
(reactivity.)Tj
/F12 1 Tf
-32.3317 -1.3039 Td
[()39()-13()14()7()20()]TJ
/F8 1 Tf
3.2314 0 Td
(carbamylation)Tj
5.9641 0 Td
(of)Tj
1.0148 0 Td
(proteins)Tj
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(FCS)Tj
1.8878 0 Td
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1.7008 0 Td
(performed)Tj
4.4674 0 Td
(by)Tj
1.1792 0 Td
(incubating)Tj
4.507 0 Td
(4)Tj
0.6974 0 Td
(mg/mL)Tj
3.1917 0 Td
(FCS)Tj
1.8879 0 Td
(with)Tj
-35.4498 -1.2982 Td
(1M)Tj
1.5873 0 Td
(KCNO,)Tj
3.2655 0 Td
(or)Tj
1.0999 0 Td
(with)Tj
1.9955 0 Td
(1M)Tj
1.5874 0 Td
(KCl)Tj
1.8029 0 Td
(as)Tj
1.0148 0 Td
(control,)Tj
3.3505 0 Td
(during)Tj
2.9253 0 Td
(15)Tj
1.1736 0 Td
(hours)Tj
2.5114 0 Td
(at)Tj
0.9525 0 Td
(37C)Tj
2.228 0 Td
(as)Tj
1.0148 0 Td
(previously)Tj
4.3483 0 Td
(described)Tj
4.0535 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(].)Tj
-34.9112 -1.2983 Td
(After)Tj
2.2847 0 Td
(incubation,)Tj
4.7735 0 Td
(the)Tj
1.4683 0 Td
(samples)Tj
3.3846 0 Td
(were)Tj
2.1203 0 Td
(dialyzed)Tj
3.5149 0 Td
(against)Tj
3.0274 0 Td
(H)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 413.4614 237.3165 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 416.9763 239.0173 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(O)Tj
0.9694 0 Td
(with)Tj
1.9956 0 Td
(0.25)Tj
1.8708 0 Td
(NaCl)Tj
2.3017 0 Td
(during)Tj
2.9254 0 Td
(24)Tj
1.1735 0 Td
(hours)Tj
2.5172 0 Td
(at)Tj
-35.4498 -1.3039 Td
(4C.)Tj
1.9729 0 Td
(The)Tj
1.7858 0 Td
(efficiency)Tj
4.0252 0 Td
(and)Tj
1.7291 0 Td
(percentage)Tj
4.5524 0 Td
(of)Tj
1.0148 0 Td
(carbamylation)Tj
5.9641 0 Td
(was)Tj
1.7007 0 Td
(corroborated)Tj
5.4651 0 Td
(by)Tj
1.1849 0 Td
(HPLC)Tj
2.7439 0 Td
(as)Tj
1.0148 0 Td
(previously)Tj
-33.1537 -1.2982 Td
(done)Tj
2.228 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(].)Tj
2.075 0 Td
(A)Tj
/F12 1 Tf
0.9014 0 Td
[( )17()4()4(\n)13()18()20()11()]TJ
4.0081 0 Td
[(\r)]TJ
/F8 1 Tf
1.1509 0 Td
(amino)Tj
2.795 0 Td
(acid)Tj
1.8708 0 Td
(analyzer)Tj
3.5433 0 Td
(\(Biochrom,)Tj
4.7904 0 Td
(UK\))Tj
1.9729 0 Td
(was)Tj
1.6951 0 Td
(used)Tj
2.0636 0 Td
(to)Tj
1.0205 0 Td
(determine)Tj
4.3256 0 Td
(the)Tj
-34.4406 -1.2983 Td
(change)Tj
3.0387 0 Td
(of)Tj
1.0148 0 Td
(lysine)Tj
2.5228 0 Td
(to)Tj
1.0262 0 Td
(homocitrulline)Tj
6.2021 0 Td
(among)Tj
2.9934 0 Td
(the)Tj
1.4684 0 Td
(FCS)Tj
1.8878 0 Td
(proteins.)Tj
-18.958 -1.3039 Td
(IgG)Tj
1.7405 0 Td
(anti-CarPA)Tj
4.8302 0 Td
(were)Tj
2.126 0 Td
(quantified)Tj
4.3086 0 Td
(by)Tj
1.1792 0 Td
(ELISA)Tj
2.829 0 Td
(as)Tj
1.0148 0 Td
(previously)Tj
4.3482 0 Td
(described)Tj
4.0535 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(].)Tj
3.2541 0 Td
(Separate)Tj
3.6 0 Td
(Nunc)Tj
-34.4803 -1.2983 Td
(MaxiSorp)Tj
4.1499 0 Td
(flat-bottom)Tj
4.7735 0 Td
(96)Tj
1.1736 0 Td
(well)Tj
1.8198 0 Td
(plates)Tj
2.5001 0 Td
(were)Tj
2.1203 0 Td
(coated)Tj
2.8347 0 Td
(with)Tj
1.9955 0 Td
(carbamylated)Tj
5.5955 0 Td
(and)Tj
1.7291 0 Td
(native)Tj
2.6476 0 Td
(FCS)Tj
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2000 Adobe Systems Incorporated. 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