İleri Dönem Romatoid Artrit Ra Hastalarında Anti-Siklik Sitrülinlenmiş Peptid Anti-Ccp Antikorunun Hastalık Aktivitesi İle İlişkisi Ve Prognostik Değeri
Amaç: Anti-siklik sitrülinlenmiş peptid anti-CCP antikorları romatoid artrit RA tanısında son yıllarda kullanılmaya başlanmış yüksek özgüllük ve duyarlılığa sahip belirteçlerdir. Bu çalışmada ileri dönem RA hastalarında anti-CCP antikorlarının hastalık aktivitesi, radyolojik olarak saptanan eklem hasarı ile ilişkisinin ve prognostik değerinin araştırılması amaçlanmıştır.Yöntem: İleri dönem 122 RA hastası ve 50 sağlıklı kontrolde anti-CCP antikoru ve romatoid faktör RF titreleri ölçülmüştür. Hastalık aktivitesinin değerlendirilmesinde; hassas eklem sayısı HES , şiş eklem sayısı ŞES , vizuel analog skala VAS ’ya göre ağrı şiddeti, sabah tutukluğu süresi, hastaya ve hekime göre global hastalık aktivitesi skoru, 28 eklemde hastalık aktivesi skoru DAS 28 , eritrosit sedimantasyon hızı ESH , lökosit sayısı, C-reaktif protein CRP düzeyi kullanılmıştır. Fonksiyonel aktivite sorgulanması Health Assessment Questionnaire HAQ , eklem hasarının radyolojik değerlendirilmesi Larsen Yöntemi ile yapılmıştır.Bulgular: Hastaların %66.4’ünde anti-CCP antikoru, %59’unda RF pozitif bulunmuştur. RA hastalarında; anti-CCP titresi ile RF titresi r=0.582, p
Association of anti-cyclic citrulinated peptide anti-CCP antibody with disease activity in advanced rheumatoid arthritis patients and its prognostic value
Objective: Anti-cyclic citrullinated peptide anti-CCP antibodies are highly specific and sensitive markers which are used in the diagnosis of rheumatoid arthritis RA , in recent years. In this study it was aimed to investigate the association of anti-CCP antibodies with disease activity and radiological joint damage in advanced RA patients and the prognostic value of anti-CCP antibodies. Method: Titers of anti- CCP antibodies and rheumatoid factor RF in 122 advanced RA patients and 50 healthy controls had been searched. In order to determine the activity of the disease , tender joints count TJC , swollen joints count SJC , visual analog scale VAS for pain, duration of morning stiffness, patient’s and physician’s global assessment, disease activity score for 28 joints DAS 28 , erythrocyte sedimentation rate ESR , leukocyte count and C-reactive protein CRP were evaluated. Functional activity assessment and radiological joint damage were carried out according to the Health Assessment Questionnaire HAQ and Larsen method, respectively.Results: 66.4% were positive for anti-CCP antibodies and 59% were positive for RF of the patients. In patients with RA, significant correlations were found between serum anti-CCP level and RF level r=0.582, p
___
- Harris ED Jr. Rheumatoid arthritis. Pathophysiology and
implications for therapy. N Engl J Med. 1990; 322(18):
1277-89.
- Gümüşdiş G. Romatoid artrit. Gümüşdiş G, Doğanavşargil
E (editörler). Klinik Romatoloji. İstanbul: Deniz Matbaası
1999; 269-78.
- Hochberg MC. Adult and juvenile rheumatoid arthritis:
current epidemiologic concepts. Epidemiol Rev. 1981;3:
27-44.
- Buch M, Emery P. The aetiology and pathogenesis of
rheumatoid arthritis. Hosp Pharm 2002; 9: 5-10.
- Weissmann G. Pathogenesis of rheumatoid arthritis. J
Clin Rheumatol. 2004 ;10(3 Suppl): S26-31.
- Griesmacher A, Peichl P. Autoantibodies associated with
rheumatic diseases. Clin Chem Lab Med. 2001 ; 39(3):
189-208.
- Kastbom A, Strandberg G, Lindroos A, Skogh T. AntiCCP antibody test predicts the disease course during
3 years in early rheumatoid arthritis (the Swedish TIRA
project). Ann Rheum Dis. 2004 ;63(9): 1085-9.
- del Val del Amo N, Ibanez Bosch R, Fito Manteca C,
Gutierrez Polo R, Loza Cortina E. Anti-cyclic citrullinated
peptide antibody in rheumatoid arthritis: relation with
disease aggressiveness. Clin Exp Rheumatol. 2006;
24(3): 281-6.
- van Venrooij WJ, Pruijn GJ. Citrullination: a small
change for a protein with great consequences for
rheumatoid arthritis. Arthritis Res. 2000;2(4): 249-51.
Epub 2000 May 24.
- Khosla P, Shankar S, Duggal L. Anti CCP antibodies in
rheumatoid arthritis. J Indian Rheumatol Assoc 2004 :
12 : 143 -46.
- van Venrooij WJ, Hazes JM, Visser H. Anticitrullinated
protein/peptide antibody and its role in the diagnosis
and prognosis of early rheumatoid arthritis. Neth J Med.
2002; 60(10): 383-8.
- López-Hoyos M, Marquina R, Tamayo E et al. Defects in
the regulation of B cell apoptosis are required for the
production of citrullinated peptide autoantibodies in
mice. Arthritis Rheum. 2003; 48(8):2353-61.
- Vossenaar ER, Nijenhuis S, Helsen MM et al. Citrullination
of synovial proteins in murine models of rheumatoid
arthritis. Arthritis Rheum. 2003; 48(9): 2489-500.
- Zhou Z, Ménard HA. Autoantigenic posttranslational
modifications of proteins: does it apply to rheumatoid
arthritis? Curr Opin Rheumatol. 2002; 14(3): 250-3.
- Suzuki A, Yamada R, Chang X et al. Functional
haplotypes of PADI4, encoding citrullinating enzyme
peptidylarginine deiminase 4, are associated with
rheumatoid arthritis. Nat Genet. 2003; 34(4): 395-402.
- Schellekens GA, de Jong BAW, Van den Hoogen FHJ, Van
de PutteLBA, Van Venrooij WJ. Citrulline is an essential
constituent of antigenic determinants recognized by
rheumatoid arthritis-specific autoantibodies. J Clin
Invest 1998, 101(1): 273–81.
- Sebbag M, Simon M, Vincent C et al. The antiperinuclear
factor and the so-called antikeratin antibodies are the
same rheumatoid arthritis-specific autoantibodies. J
Clin Invest. 1995; 95(6): 2672-9.
- Schellekens GA, Visser H, de Jong BA et al. The
diagnostic properties of rheumatoid arthritis antibodies
recognizing a cyclic citrullinated peptide. Arthritis
Rheum. 2000 43(1): 155-63.
- Zendman AJ, van Venrooij WJ, Pruijn GJ. Use and
significance of anti-CCP autoantibodies in rheumatoid
arthritis. Rheumatology (Oxford). 2006; 45(1): 20-5.
- Lee DM, Schur PH. Clinical utility of the anti-CCP assay
in patients with rheumatic diseases. Ann Rheum Dis.
2003; 62(9): 870–4.
- Suzuki K, Sawada T, Murakami A et al. High diagnostic
performance of ELISA detection of antibodies to
citrullinated antigens in rheumatoid arthritis. Scand J
Rheumatol. 2003; 32(4): 197–204.
- Vasishta A. Diagnosing early-onset rheumatoid arthritis:
the role of anti-CCP antibodies. Am Clin Lab. 2002;
21(7): 34–6.
- Pinheiro GC, Scheinberg M A, Aparecida da Silva M,
Maciel S. Anti-cyclic citrullinated peptide antibodies in
advanced rheumatoid arthritis. Ann Intern Med. 2003;
139(3): 234–5.
- Rantapää-Dahlqvist S, de Jong BA, Berglin E et al.
Antibodies against cyclic citrullinated peptide and
IgA rheumatoid factor predict the development of
rheumatoid arthritis. Arthritis Rheum. 2003; 48(10):
2741–9.
- Kroot EJ, de Jong BA, van Leeuwen MA et al. The
prognostic value of anti-cyclic citrullinated peptide
antibody in patients with recent-onset rheumatoid
arthritis. Arthritis Rheum. 2000; 43(8): 1831-5.
- Nielen MM, van Schaardenburg D, Reesink HW et al.
Specific autoantibodies precede the symptoms of
rheumatoid arthritis: a study of serial measurements
in blood donors. Arthritis Rheum. 2004; 50(2): 380-6.
- Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JMW.
How to diagnose rheumatoid arthritis early; a prediction
model for persistent (erosive) arthritis. Arthritis Rheum
2002; 46: 357-65.
- van Gaalen FA, Linn-Rasker SP, van Venrooij WJ et al.
Autoantibodies to cyclic citrullinated peptides predict
progression to rheumatoid arthritis in patients with
undifferentiated arthritis: a prospective cohort study.
Arthritis Rheum. 2004; 50(3): 709-15.
- Goldbach-Mansky R, Lee J, McCoy A et al. Rheumatoid
arthritis associated autoantibodies in patients with
synovitis of recent onset. Arthritis Res. 2000; 2(3): 236-
43.
- Bukhari M, Harrison B, Lunt M, Scott DG, Symmons
DP, Silman AJ. Time to first occurrence of erosions in
inflammatory polyarthritis: results from a prospective
community-based study. Arthritis Rheum. 2001; 44(6):
1248-53.
- Arnett FC, Edworthy SM, Bloch DA et al. The American
Rheumatism Association 1987 revised criteria for the
classification of rheumatoid arthritis. Arthritis Rheum.
1988; 31(3): 315-24.
- Smolen JS, Breedveld FC, Eberl G et al. Validity and
reliability of the twenty-eight-joint count for the
assessment of rheumatoid arthritis activity. Arthritis
Rheum. 1995; 38(1): 38-43.
- Sriwatanakul K, Kelvie W, Lasagna L, Calimlim JF, Weis
OF, Mehta G. Studies with different types of visual
analog scales for measurement of pain. Clin Pharmacol
Ther. 1983; 34(2): 234-9.
- Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen
MA, van de Putte LB, van Riel PL. Modified disease
activity scores that include twenty-eight-joint
counts. Development and validation in a prospective
longitudinal study of patients with rheumatoid arthritis.
Arthritis Rheum. 1995; 38(1): 44-8.
- Fries JF, Spitz P, Kraines RG, Holman HR. Measurement
of patient outcome in arthritis. Arthritis Rheum. 1980;
23(2): 137-45.
- Boini S, Guillemin F. Radiographic scoring methods as
outcome measures in rheumatoid arthritis: properties
and advantages. Ann Rheum Dis. 2001; 60(9): 817-27.
- Larsen A, Dale K, Eek M. Radiographic evaluation of
rheumatoid arthritis and related conditions by standard
reference films. Acta Radiol Diagn (Stockh). 1977;
18(4): 481-91.
- Larsen A. How to apply Larsen score in evaluating
radiographs of rheumatoid arthritis in long-term
studies. J Rheumatol. 1995; 22(10): 1974-5.
- Mimori T. Clinical significance of anti-CCP antibodies
in rheumatoid arthritis. Intern Med. 2005; 44(11):
1122-6.
- Mikuls TR, O'Dell JR, Stoner JA et al. Association of
rheumatoid arthritis treatment response and disease
duration with declines in serum levels of IgM rheumatoid
factor and anti-cyclic citrullinated peptide antibody.
Arthritis Rheum. 2004; 50(12): 3776-82.
- Bobbio-Pallavicini F, Alpini C, Caporali R, Avalle S,
Bugatti S, Montecucco C. Autoantibody profile in
rheumatoid arthritis during long-term infliximab
treatment. Arthritis Res Ther. 2004; 6(3): R264-72.
- De Rycke L, Peene I, Hoffman IE et al. Rheumatoid
factor and anticitrullinated protein antibodies in
rheumatoid arthritis: diagnostic value, associations
with radiological progression rate, and extra-articular
manifestations. Ann Rheum Dis. 2004; 63(12): 1587-93.
- Vallbracht I, Rieber J, Oppermann M, Förger F, Siebert
U, Helmke K. Diagnostic and clinical value of anticyclic citrullinated peptide antibodies compared with
rheumatoid factor isotypes in rheumatoid arthritis. Ann
Rheum Dis. 2004; 63(9): 1079-84.
- Zeng X, Ai M, Tian X et al. Diagnostic value of anticyclic citrullinated Peptide antibody in patients with
rheumatoid arthritis. J Rheumatol. 2003; 30(7): 1451-5.
- Inanc N, Dalkilic E, Kamali S et al. Anti-CCP antibodies
in rheumatoid arthritis and psoriatic arthritis. Clin
Rheumatol. 2007; 26(1): 17-23.
- Bongi SM, Manetti R, Melchiorre D et al. Anti-cyclic
citrullinated peptide antibodies are highly associated
with severe bone lesions in rheumatoid arthritis antiCCP and bone damage in RA. Autoimmunity. 2004;
37(6-7): 495-501.
- Forslind K, Ahlmen M, Eberhardt K, Hafstrom I, Svensson
B; BARFOT Study Group. Prediction of radiological
outcome in early rheumatoid arthritis in clinical
practice: role of antibodies to citrullinated peptides
(anti-CCP). Ann Rheum Dis. 2004; 63(9): 1090-5.
- Ronnelid J, Wick MC, Lampa J et al. Longitudinal
analysis of citrullinated protein/peptide antibodies
(anti-CP) during 5 year follow up in early rheumatoid
arthritis: anti-CP status predicts worse disease activity
and greater radiological progression. Ann Rheum Dis.
2005; 64(12): 1744-9.
- Dorner T, Egerer K, Feist E, Burmester GR. Rheumatoid
factor revisited. Curr Opin Rheumatol. 2004; 16(3):
246-53.
- Masi AT, Maldonado-Cocco JA, Kaplan SB, Feigenbaum
SL, Chandler RW. Prospective study of the early course
of rheumatoid arthritis in young adults: comparison of
patients with and without rheumatoid factor positivity
at entry and identification of variables correlating with
outcome. Semin Arthritis Rheum. 1976; 4(4): 299-326.
- van der Helm-van Mil AH, Verpoort KN, Breedveld
FC, Toes RE, Huizinga TW. Antibodies to citrullinated
proteins and differences in clinical progression of
rheumatoid arthritis. Arthritis Res Ther. 2005; 7(5):
R949-58
- Bas S, Genevay S, Meyer O, Gabay C. Anti-cyclic
citrullinated peptide antibodies, IgM and IgA rheumatoid
factors in the diagnosis and prognosis of rheumatoid
arthritis. Rheumatology (Oxford). 2003; 42(5): 677-80.
- Samanci N, Ozdem S, Akbas H et al. Diagnostic value
and clinical significance of anti-CCP in patients with
advanced rheumatoid arthritis. J Natl Med Assoc. 2005;
97(8): 1120-6.
- Quinn MA, Gough AK, Green MJ et al. Anti-CCP antibodies
measured at disease onset help identify seronegative
rheumatoid arthritis and predict radiological and
functional outcome. Rheumatology (Oxford). 2006;
45(4): 478-80.
- Mottonen TT. Prediction of erosiveness and rate of
development of new erosions in early rheumatoid
arthritis. Ann Rheum Dis. 1988; 47(8): 648-53.
- van der Heijde DM. Joint erosions and patients with
early rheumatoid arthritis. Br J Rheumatol. 1995; 34
Suppl 2: 74-8.
- Dorner T, Egerer K, Feist E, Burmester GR. Rheumatoid
factor revisited. Curr Opin Rheumatol. 2004; 16(3):
246-53.
- Bas S, Perneger TV, Seitz M, Tiercy JM, Roux-Lombard
P, Guerne PA. Diagnostic tests for rheumatoid arthritis:
comparison of anti-cyclic citrullinated peptide
antibodies, anti-keratin antibodies and IgM rheumatoid
factors. Rheumatology (Oxford). 2002; 41(7): 809-14.
- Vittecoq O, Pouplin S, Krzanowska K et al. Rheumatoid
factor is the strongest predictor of radiological
progression of rheumatoid arthritis in a three-year
prospective study in community-recruited patients.
Rheumatology (Oxford). 2003; 42(8): 939-46.
- Jansen LM, van Schaardenburg D, van der HorstBruinsma I, van der Stadt RJ, de Koning MH, Dijkmans
BA. The predictive value of anti-cyclic citrullinated
peptide antibody in early arthritis. J Rheumatol 2003;
30: 1691-5.
- Vencovsky J, Machacek S, Sedova L et al. Autoantibodies
can be prognostic markers of an erosive disease in
early rheumatoid arthritis. Ann Rheum Dis. 2003; 62(5):
427-30.
- Meyer O, Labarre C, Dougados M et al. Anticitrullinated
protein/peptide antibody assays in early rheumatoid
arthritis for predicting five year radiographic damage.
Ann Rheum Dis. 2003; 62(2): 120-6.
- Berglin E, Johansson T, Sundin U et al. Radiological
outcome in rheumatoid arthritis is predicted by
presence of antibodies against cyclic citrullinated
peptide before and at disease onset, and by IgA-RF at
disease onset. Ann Rheum Dis. 2006; 65(4): 453-8.
- Greiner A, Plischke H, Kellner H, Gruber R. Association
of anti-cyclic citrullinated peptide antibodies, anticitrullin antibodies, and IgM and IgA rheumatoid
factors with serological parameters of disease
activity in rheumatoid arthritis. Ann N Y Acad Sci.
2005; 1050: 295-303.