rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2013-1499rsp-1315Research ArticleСтатьиArticlesДеструкция костной ткани при ревматоидном артрите: роль аутоантителBone destruction in rheumatoid arthritis: role of autoantibodiesAvdeyevaAnastasia SergeyevnaAvdeyevaAnastasia Sergeyevna9056249400@mail.ruАлександроваЕлена НиколаевнаAleksandrovaE N-НовиковА. А.NovikovA A-СмирновА. В.SmirnovA V-ЧеркасоваМ. В.CherkasovaM V-НасоновЕвгений ЛьвовичNasonovE L-201315062013513№3 (2013)267271Copyright © Avdeyeva A.S., Александрова Е.Н., Новиков А.А., Смирнов А.В., Черкасова М.В., Насонов Е.Л., 20132013Avdeyeva A.S., Александрова Е.Н., Новиков А.А., Смирнов А.В., Черкасова М.В., Насонов Е.Л.Avdeyeva A.S., Aleksandrova E.N., Novikov A.A., Smirnov A.V., Cherkasova M.V., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1315

Цель — оценить взаимосвязь между уровнем антител к циклическому цитруллинированному пептиду (АЦЦП), модифицированному цитруллинированному виментину (АМЦВ), ревматоидным фактором (РФ) и рентгенологическими признаками деструктивных изменений в суставах при РА. Материал и методы. Обследовано 114 больных РА. Все больные получали терапию базисными противовоспалительными препаратами и 61,4% — глюкокортикоиды. Определение СОЭ осуществляли методом Вестергрена, сывороточную концентрацию АМЦВ (ЕД/мл) — методом иммуноферментного анализа (ИФА), уровень АЦЦП (ЕД/мл) — электрохемилюминесцентным методом и методом ИФА. Для количественной оценки рентгенологических изменений использовался модифицированный метод Шарпа. Результаты. Значение общего счета Шарпа (ОСШ; Me [25-й; 75-й перцентили]) составило — 89 [57; 117], количество эрозий — 9 [3; 27], количество сужений — 76 [51; 99], уровень АМЦВ — 470,2 [106,9; 1000] ЕД/мл. В зависимости от уровня позитивности по IgM РФ, АЦЦП и АМЦВ все пациенты были разделены на группы. Среди высоко позитивных по АМЦВ больных (n=80) отмечалось большее значение ОСШ (96,5 [66,0; 120,0]), количества сужений (82,0 [60,5; 105,5]) и более высокая воспалительная активность заболевания (СОЭ 40 [30; 61]) по сравнению с негативными/низкопозитивными больными (57 [31; 88], 50 [29; 82], 30 [21; 48,5] соответственно, p<0,05, n=25). Достоверных различий в суставной деструкции в группах больных в зависимости от позитивности по IgM РФ и АЦЦП выявлено не было. Заключение. АМЦВ в большей степени влияет на деструкцию костной ткани, а также ассоциируется с более высокой воспалительной активностью заболевания по сравнению с АЦЦП.

Objective: to assess an association between the levels of anti-cyclic citrullinated peptide antibodies (anti-CCP), anti-modified citrullinated vimentin antibodies (anti-MCV), rheumatoid factor (RF), and X-ray signs of destructive changes in RAjoints. Subjects and methods. One hundred and fourteen patients with RA were examined. All the patients received therapy with disease-modifying antirheumatic drugs and 61.4% took glucocorticoids. The investigators determined erythrocyte sedimentation rate (ESR) by the Westergren method, serum anti-MCV concentrations (U/ml) by enzyme immunoassay (EIA), anti-CCP levels by electrochemiluminescence and EIA. The modified Sharp method was used to quantify X-ray changes. Results. The total Sharp score (TSS; Me [the 25th and 75th percentile]) was 89 [57; 117]; the number of erosions and stenoses was 9 [3; 27] and 76 [51; 99], respectively; anti-MCV levels were 470.2 [106.9; 1000] U/ml. According to the level of RF IgM-, anti-CCP-, and anti-MCV-positivity, all the patients were divided into groups. High anti-MCV positive patients (n = 80) were observed to have higher TSS (96.5 [66.0; 120.0]), a larger number of stenosis (82.0 [60.5; 105.5]), and greater inflammatory disease activity (ESR, 40 [30; 61]) than negative/low positive patients (n = 25) who had 57 [31; 88], 50 [29; 82], 30 [21; 48.5] respectively; p < 0.05). No significant differences in joint destruction were found in the patient groups according to RF IgMand anti-CCP-positivity. Conclusion. Anti-MCV shows a greater degree of bone destruction and is associated with higher inflammatory disease activity than anti-CCP.

ревматоидный артритдеструкция суставовIgM ревматоидный факторантитела к циклическому цитруллинированному пептидуантитела к модифицированному цитруллинированному виментинумаркеры воспаленияrheumatoid arthritisjoint destructionIgM rheumatoid factoranti-cyclic citrullinated peptide antibodiesanti-modified citrullinated vimentin antibodiesinflammatory markersReferences<div><p>Новиков А.А., Александрова Е.Н., Черкасова М.В. и др. Современные методы лабораторной диагностики ревматоидного артрита. Науч-практич ревматол 2010;1:31—45.</p><p>Aggarwal R., Liao K., Nair R. et al. Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis. Arthr Rheum 2009;61:1472—83.</p><p>Song Y.W., Kang E.H. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM 2010;103:139—46.</p><p>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;62:120—6.</p><p>Klareskog L., Catrina A.I., Paget S. Rheumatoid arthritis. Lancet 2009;373:659—72.</p><p>Ursum J., Bos W.H., van de Stadt R.J. et al. Different properties of ACPA and IgM-RF derived from a large dataset: further evidence o two distinct autoantibody systems. Arthr Res Ther 2009;11:7.</p><p>Valesini G., Alessandri C. Anticitrullinate antibodies and rheumatoid factors: two distinct autoantibody systems. Arthr Res Ther 2009;11:125.</p><p>Riedemann J.P., Munoz S., Kavanaugh A. The use of second generation anti-CCP antibody (anti-CCP2) testing in rheumatoid arthritis — a systematic review. Clin Exp Rheumatol 2005;2:69—76.</p><p>Turesson C., Jacobsson L.T., Sturfelt G. et al. Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 2007;66:59—64.</p><p>Machold K.P., Stamm T.A., Nell V.P. et al. Very recent onset rheumatoid arthritis: clinical and serological patient characteristics associated with radiographic progression over the first years of disease. Rheumatology (Oxford) 2007;46:342—9.</p><p>Новиков А.А., Александрова Е.Н., Каратеев Д.Е. и др. Диагностическое значение антител к модифицированному циклическому виментину при раннем ревматоидном артрите. Клин лаб диагн 2008;8:27—9.</p><p>Schett G. Cells of the synovium in rheumatoid arthritis. Osteoclasts. Arthr Res Ther 2007;9:203.</p><p>Gravallese E.M., Manning C., Tsay A. et al. Synovial tissue in rheumatoid arthritis is asource of osteoclast differentiation factor. Arthr Rheum 2000;43:250—8.</p><p>Shigeyama Y., Pap T., Kunzler P. et al. Expression of osteoclast differentiation factor in rheumatoid arthritis. Arthr Rheum 2000;43:2523—30.</p><p>Sato K., Suematsu A., Okamoto K. et al. Th17 functions as an osteoclastogenic T helper cell subset that links T cell activation and bone destruction. J Exp Med 2006;2203:2673—82.</p><p>Seitz M., Loetscher P., Fey M.F. et al. Constitutive mRNA and protein production of macrophage colony-stimulating factor but not of other cytokines by synovial fibroblasts from rheumatoid arthritis and osteoarthritis patients. Br J Rheumatol 1994;33:613—9.</p><p>Stolina M., Adamu S., Ominsky M. et al. RANKL is a marker and mediator of local and systemic bone loss in two rat models of inflammatory arthritis. J Bone Miner Res 2005;20:1756—65.</p><p>Lam J., Takeshita S., Barker J.E. et al. TNF-alpha induces osteo-clastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 2000;106:1481—8.</p><p>Lubberts E., van den Bersselaar L., Oppers-Walgreen B. et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance. J Immunol 2003;170:2655—62.</p><p>Wei S., Kitaura H., Zhou P. et al. Teitelbaum SL: IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 2005;115:282—90.</p><p>Azuma Y., Kaji K., Katogi R. et al. Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts. J Biol Chem 2000;275:4858—64.</p><p>Matsumoto M., Sudo T., Maruyama M. et al. Activation of p38 mitogen-activated protein kinase is crucial in osteoclastogenesis induced by tumor necrosis factor. FEBS Lett 2000;486:23—8.</p><p>Harre U., Georgess, D., Bang H. et al. Induction of osteoclastoge-nesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 2012;122:1791—802.</p><p>Harre U., Georgess D., Axmann R. et al. Anti-citrullinated protein antibodies directly induce bone loss in rheumatoid arthritis. Ann Rheum Dis 2012;71(Suppl 3):59.</p><p>Van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 1999;26:743—5.</p><p>Смирнов А.В. Атлас рентгенологической диагностики ревматоидного артрита. М.: ИМА-ПРЕСС, 2009.</p><p>Syversen S., Goll G., van der Heijde D. et al. Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study. Ann Rheum Dis. 2010;69:345—51.</p><p>Mathsson L., Mullazehi M., Wick M. et al. Antibodies against cit-rullinated vimentin in rheumatoid arthritis. Arthr Rheum 2008;58:36—45.</p><p>Mansour H., Metwaly K., Hassan I. et al. Antibodies to mutated citrullinated vimentin in rheumatoid arthritis: diagnostic value, association with radiological damage and axial skeleton affection. Clin Med: Arthr Musculoskelet Dis 2010;3:33—42.</p><p>Boire G., Gosette P., Combe B. et al. Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients witch recent-onset polyarthritis. Arthr Res Ther 2005;7:529—603.</p><p>Vossenaar E.R., Despres N., Lapointe E. et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthr Res Ther 2004;6:142—50.</p><p>Welsing P., Landewe R., van Riel P. et al. The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis. Arthr Rheum 2004;50:2082—93.</p><p>Plant M.J., Williams A.L., O'Sullivan M.M. et al. Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis. Arthr Rheum 2000;43:1473—7.</p><p>Van Leeuwen M.A., van Rijswijk M.H., van der Heijde D.M. et al. The acute-phase response in relation to radiographic progression in early rheumatoid arthritis: a prospective study during the first three years of the disease. Br J Rheumatol 1993;32:9—13.</p><p>Van der Heide A., Remme C.A., Hofman D.M. et al. Prediction of progression of radiologic damage in newly diagnosed rheumatoid arthritis. Arthr Rheum 1995;38:1466—74.</p><p>Pepys M.B., Hirschfield G.M. C-reactive protein: a critical update. J Clin Invest 2003;111:1805—12.</p><p>Combe B., Dougados M., Goupille P. et al. Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study. Arthr Rheum 2001;44:1736—43.</p><p>Bang H., Lü thke K., Gauliard A. et al. Mutated citrullinated vimentin as a candidate autoantigen for diagnosis and monitoring of disease activity in rheumatoid arthritis. Ann Rheum Dis 2006;65(Suppl II):144.</p><p>Roland P., Mignot S., Bruns A. Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthr Res Ther 2008;10:142.</p></div><br /><div><p>Новиков А.А., Александрова Е.Н., Черкасова М.В. и др. Современные методы лабораторной диагностики ревматоидного артрита. Науч-практич ревматол 2010;1:31—45.</p><p>Aggarwal R., Liao K., Nair R. et al. Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis. Arthr Rheum 2009;61:1472—83.</p><p>Song Y.W., Kang E.H. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM 2010;103:139—46.</p><p>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;62:120—6.</p><p>Klareskog L., Catrina A.I., Paget S. Rheumatoid arthritis. Lancet 2009;373:659—72.</p><p>Ursum J., Bos W.H., van de Stadt R.J. et al. Different properties of ACPA and IgM-RF derived from a large dataset: further evidence o two distinct autoantibody systems. Arthr Res Ther 2009;11:7.</p><p>Valesini G., Alessandri C. Anticitrullinate antibodies and rheumatoid factors: two distinct autoantibody systems. Arthr Res Ther 2009;11:125.</p><p>Riedemann J.P., Munoz S., Kavanaugh A. The use of second generation anti-CCP antibody (anti-CCP2) testing in rheumatoid arthritis — a systematic review. Clin Exp Rheumatol 2005;2:69—76.</p><p>Turesson C., Jacobsson L.T., Sturfelt G. et al. Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 2007;66:59—64.</p><p>Machold K.P., Stamm T.A., Nell V.P. et al. Very recent onset rheumatoid arthritis: clinical and serological patient characteristics associated with radiographic progression over the first years of disease. Rheumatology (Oxford) 2007;46:342—9.</p><p>Новиков А.А., Александрова Е.Н., Каратеев Д.Е. и др. Диагностическое значение антител к модифицированному циклическому виментину при раннем ревматоидном артрите. Клин лаб диагн 2008;8:27—9.</p><p>Schett G. Cells of the synovium in rheumatoid arthritis. Osteoclasts. Arthr Res Ther 2007;9:203.</p><p>Gravallese E.M., Manning C., Tsay A. et al. Synovial tissue in rheumatoid arthritis is asource of osteoclast differentiation factor. Arthr Rheum 2000;43:250—8.</p><p>Shigeyama Y., Pap T., Kunzler P. et al. Expression of osteoclast differentiation factor in rheumatoid arthritis. Arthr Rheum 2000;43:2523—30.</p><p>Sato K., Suematsu A., Okamoto K. et al. Th17 functions as an osteoclastogenic T helper cell subset that links T cell activation and bone destruction. J Exp Med 2006;2203:2673—82.</p><p>Seitz M., Loetscher P., Fey M.F. et al. Constitutive mRNA and protein production of macrophage colony-stimulating factor but not of other cytokines by synovial fibroblasts from rheumatoid arthritis and osteoarthritis patients. Br J Rheumatol 1994;33:613—9.</p><p>Stolina M., Adamu S., Ominsky M. et al. RANKL is a marker and mediator of local and systemic bone loss in two rat models of inflammatory arthritis. J Bone Miner Res 2005;20:1756—65.</p><p>Lam J., Takeshita S., Barker J.E. et al. TNF-alpha induces osteo-clastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 2000;106:1481—8.</p><p>Lubberts E., van den Bersselaar L., Oppers-Walgreen B. et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance. J Immunol 2003;170:2655—62.</p><p>Wei S., Kitaura H., Zhou P. et al. Teitelbaum SL: IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 2005;115:282—90.</p><p>Azuma Y., Kaji K., Katogi R. et al. Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts. J Biol Chem 2000;275:4858—64.</p><p>Matsumoto M., Sudo T., Maruyama M. et al. Activation of p38 mitogen-activated protein kinase is crucial in osteoclastogenesis induced by tumor necrosis factor. FEBS Lett 2000;486:23—8.</p><p>Harre U., Georgess, D., Bang H. et al. Induction of osteoclastoge-nesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 2012;122:1791—802.</p><p>Harre U., Georgess D., Axmann R. et al. Anti-citrullinated protein antibodies directly induce bone loss in rheumatoid arthritis. Ann Rheum Dis 2012;71(Suppl 3):59.</p><p>Van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 1999;26:743—5.</p><p>Смирнов А.В. Атлас рентгенологической диагностики ревматоидного артрита. М.: ИМА-ПРЕСС, 2009.</p><p>Syversen S., Goll G., van der Heijde D. et al. Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study. Ann Rheum Dis. 2010;69:345—51.</p><p>Mathsson L., Mullazehi M., Wick M. et al. Antibodies against cit-rullinated vimentin in rheumatoid arthritis. Arthr Rheum 2008;58:36—45.</p><p>Mansour H., Metwaly K., Hassan I. et al. Antibodies to mutated citrullinated vimentin in rheumatoid arthritis: diagnostic value, association with radiological damage and axial skeleton affection. Clin Med: Arthr Musculoskelet Dis 2010;3:33—42.</p><p>Boire G., Gosette P., Combe B. et al. Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients witch recent-onset polyarthritis. Arthr Res Ther 2005;7:529—603.</p><p>Vossenaar E.R., Despres N., Lapointe E. et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthr Res Ther 2004;6:142—50.</p><p>Welsing P., Landewe R., van Riel P. et al. The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis. Arthr Rheum 2004;50:2082—93.</p><p>Plant M.J., Williams A.L., O'Sullivan M.M. et al. Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis. Arthr Rheum 2000;43:1473—7.</p><p>Van Leeuwen M.A., van Rijswijk M.H., van der Heijde D.M. et al. The acute-phase response in relation to radiographic progression in early rheumatoid arthritis: a prospective study during the first three years of the disease. Br J Rheumatol 1993;32:9—13.</p><p>Van der Heide A., Remme C.A., Hofman D.M. et al. Prediction of progression of radiologic damage in newly diagnosed rheumatoid arthritis. Arthr Rheum 1995;38:1466—74.</p><p>Pepys M.B., Hirschfield G.M. C-reactive protein: a critical update. J Clin Invest 2003;111:1805—12.</p><p>Combe B., Dougados M., Goupille P. et al. Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study. Arthr Rheum 2001;44:1736—43.</p><p>Bang H., Lü thke K., Gauliard A. et al. Mutated citrullinated vimentin as a candidate autoantigen for diagnosis and monitoring of disease activity in rheumatoid arthritis. Ann Rheum Dis 2006;65(Suppl II):144.</p><p>Roland P., Mignot S., Bruns A. Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthr Res Ther 2008;10:142.</p></div><br />

The authors declare that there are no conflicts of interest present.