rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2005-34rsp-318Research ArticleСтатьиArticlesРазновидности антифосфолипидных антител у больных системной красной волчанкой и первичным антифосфолипидным синдромомAntiphospholipide antibodies subtypes in systemic lupus erythematosus and antiphospholipid syndromeРешетнякТ. М.ReshetnyakT M-ZabekJZabekJ-АлекбероваЗемфира СадуллаевнаAlekberovaZ S-AlexandrovaE NAlexandrovaE N-VoytsehovskayaBVoytsehovskayaB-200515102005435№5 (2005)1118Copyright © Решетняк Т.М., Zabek J., Алекберова З.С., Alexandrova E.N., Voytsehovskaya B., 20052005Решетняк Т.М., Zabek J., Алекберова З.С., Alexandrova E.N., Voytsehovskaya B.Reshetnyak T.M., Zabek J., Alekberova Z.S., Alexandrova E.N., Voytsehovskaya B.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/318

Цель. Изучить частоту и клиническую значимость различных аФЛ: антител к кардиолипину (аКЛ), антител к 2-гликопротеину I (анти- (52-ГП1), антител к аннексину V (a-АН V) и аутоантител к окЛНП (а-окЛ НП) у больных СКВ с и без АФС. Материал и методы. Работа основана на результатах клинико-лабораторного исследования 68 больных (14 муж., 58 жен., средний возраст 35,2±11,4 лет), наблюдавшихся в ГУ Института ревматологии РАМН. У 45 из них была диагностирована СКВ и у 23 - ПАФС. У 24 из 45 больных СКВ имелись признаки АФС. Тромботические исходы верифицировались только при их инструментальном подтверждении. У 43 из 68 (63,2%) обследованных больных регистрировались тромбозы в анамнезе. Определение аКЛ, анти- Р2-ГП1, a-АН V, a-окЛНП в сыворотке крови проводилось иммуноферментным методом. Уровень IgG- аКЛ определялся в ГУ Институте ревматологии РАМН и в лаборатории Института ревматологии Варшавы. Исследование ВА проводилось мануально в фосфолипидзависимых тестах свертывания крови в плазме, бедной тромбоцитами Результаты. Частота выявления в крови IgG-aKJl была достоверно выше поданным исследования в ГУ Институте ревматологии РАМН и ассоциировалась с наличием АФС.Процент lgG-аКЛ - позитивности при исследовании в лаборатории Варшавы составил при СКВ -29, при СКВ+АФС- 33, при ПАФС - 39. При этом у половины больных позитивный уровень lgG-аКЛ, как и других исследованных антител, относился к сомнительным или низко-позитивным. Тромботические осложнения ассоциировались с наличием в крови IgG-анти- р2-ГП1, средний уровень этих антител в группе больных с тромбозами составил 0,292 ед ОП. (медиана -0,157; миним. значения -0,049, макс. - 0,994 и отрезок интерквартильного разброса 0,251), тогда как в группе больных без тромбозов средний уровень был 0, 178 ед. ОП (медиана -0,112; минимальные значения -0,440, макс. - 0,834 и отрезок интерквартильного разброса 0,100) (р=0,003 по Манну-Уитни). Статистической зависимости между уровнем IgG-aKfl, IgG-a-AH V и наличием тромбозов, не отмечалось однако высокие уровни антител определялись в группе пациентов с тромбозами. Прослежена связь между активностью СКВ и повышенными уровнями lgG-a-окЛНП. 16 больных СКВ с высокими уровнями IgG-a-окЛНП активность заболевания по шкале SLEDAJ 1 составила 22,6+4,34 балла против 8,7+3,52 баллов (р=0,0001) у 22 больных СКВ с негативными значениями этих антител. Заключение. Выявлена ассоциация между наличием в крови IgG-анти- Р2-ГП1 и тромбозами независимо от их локализации. У больных СКВ выявление в крови IgG-a-окЛНП ассоциировалось с активностью болезни.

Objective. То study frequency and clinical significance of different antiphospholipid antibodies (APHLA): anti- cardiolipin (АСА), anti-?2 glycoprotein (AB2), anti-annexin V (AAV) and autoantibodies to oxidized low density lipoproteins (AOLDPL) in pts with systemic lupus erythematosus (SLE) with and without antiphospholipid syndrome (APS). Material and methods. 68 pts (14 male, 54 female, mean age 35,2+11,4 years) followed up in the Institute оГ Rheumatology were included. 45 of them had SLE and 23 - primary APS. 24 from 45 SLE pts had signs of APS. Only instrumentally verified thromboembolic events were recorded. 43 from 68 (63,2%) pts had history of thrombosis. АСА, AB2, AAV and AOLDPL serum level was examined with immuno-enzyme assay. IgG АСА level was in the Institute of Rheumatology of RAMS and in the Institute of Rfeumatology of Warsaw. Lupus anticoagulant was tested with phospholipids-dependent method in platelet depleted plasma. Results. IgG АСА were more frequently revealed in the Institute of Rheumatology of RAMS and were associated with the presence of APS. In the Warsaw laboratory IgG positivity in SLE was revealed in 29%, in SLE+APS - in 33%, in primary APS - in 39%. in half of the pts IgG АСА level was doubtful or low-positive. Thromboembolic events were associated with the presence of IgG AB2 (mean level 0,292 U of OP, median 0,157, minimum - 0,049, maximum 0,994, interquartile dispersion 0,251). Mean level in the absence of thrombosis was 0, 178 U of OP (median 0,112, minimum - 0,440, maximum 0,834, interquartile dispersion 0,100), p=0,003 according to Mann-Whitney test. There was no statistical dependence between IgG АСА, IgG AAV and Ihrom- boembolic events but very high levels of antibodies were present in the group of pts with thromboses. There was a correlation between SLE activity and high AOLDPL level. Mean value of SLEDAI scale in 16 SLE pts with high AOLDPL level was 22,6+4,34 compared with 8,37+3,52 (p=0,000I) in 22 SLE pts not having these antibodies. Conclusion. Presence of IgG AB2 is associated with thromboses independently of their localization. Presence of AOLDPL was associated with disease activity.

антифосфолипидный синдромантифосфолипидные антителаантитела к р2- гликопротеину Iантитела к аннексину Уантитела к окисленным липоротеидам низкой плотностиanriphospholipid syndromeantiphospholipid antibodiesaiiti-p2 glycoprotein antibodiesanti-annex- in V antibodiesautoantibodies to oxidized low density lipoproteinsReferences<div><p>Wilson W.A., Gharavi А.Е., Koike Т. et al.International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthr. Rheum., 1999,42, 1309-1311</p><p>Asherson R.A, Cervera R. 'Primary', 'secondary' and other variants of the antiphospholipid syndrome. Lupus, 1994, 3, 293-298</p><p>Насонов Е.Л. Антифосфолипидный синдром. М.,Литгера, 2004,440с</p><p>Tsutsumi A, Matsuura Е., Ichikawa К., et al. Antibodies to beta2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus. Arthr. Rheum., 1996, 39,14661474</p><p>Balestrieri G., Tincani A., Spatola L. et al. Anti |32-glycoprotein I antibodies: a marker of antiphospholipid syndrome? Lupus, 1995, 4, 122-130</p><p>Le Tonqueze М., Salozhin K., Dueymes M.et al. Role of beta2- glycoprotein 1 in the antiphospholipid antibody binding to endothelial cells. Lupus, 1995, 4,179-186</p><p>de Groot P.G., Derksem R.H.W.M. Protein С pathway, antiphospholipid antibodies and thrombosis. Lupus, 1994, 3, 229-233</p><p>Roubey R.A. Immunology of the antiphospholipid antibody syndrome. Arthr. Rheum., 1996,39,1444-1454</p><p>Radulescu L., Stancu C., Antohe F. Antibodies against human oxidized low-density lipoprotein (LDL) as markers for human plasma modified lipipoproteins. Mcd.Sci.Monit., 2004, 10(7), 207-214</p><p>Tan E.M., Cohen A.S., Fries J.F et al.The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthr.Rheum., 1982, 25, 1271-1277</p><p>Александрова E.H., Насонов Е.Л., Ковалев В.Ю. Количественный иммуноферментный метод определения антител к кардиолипину в сыворотке крови. Клин, ревматол., 1995, 4 35-39</p><p>Brandt J.T., Triplett D.A., Aving В., Scharrer I. Criteria for the diagnosis of lupus anticoagulant: An update. Thromb. Haemost., 1995, 74, 1185-1190</p><p>Баркаган 3.C., Момот А.П. Основы диагностики нарушений гемостаза. Москва.”Ньюдиамед-АО", 1999,.215с</p><p>Harris E.N., Gharavi А.Е., Boey M.L. et al. Anticardiolipin antibodies: detection by radioimmunoassay and assotiation with thrombosis in systemic lupus erythematosus. Lancet,1983,2,1211-1214</p><p>Harris E.N., Gharavi A.E., Patel S.P., Hughes G.R.V. Anticardiolipin antibody testing. The need for standardization. Arthr. Rheum., 1987,30,835-836</p><p>Harris E.N., Gharavi A.E., Patel S.P., Hughes G.R.V. Evalution of the anticardiolipin antibody test: Report of standartization workshop held in April 1986. Clin.Expe.Immuno!., 1987,68,215222</p><p>Harris E.N., Pierangeli S., Birch D. Anticardiolipin VJel Workshop Report. Fifth International Symposium on Antiphospholipid antibodies. Am.J.Clin.Pathol., 1994,101,616624</p><p>Carreras L.O., Forastiero R.R., Martinuzzo M.E. Which are the best biological markers of the antiphospholipid syndrome? J.Autoimmunity, 2000,15,163-172</p><p>Coulam C.B., McIntyre J.A., Wagenknecht D., Rote N. Interlaboratories inconsistencies in detection of anticardiolipin antibodies. Lancet, 1990,335,865</p><p>Tincani A., Balestrieri G., Allegri F. et al. Overview on Anticardiolipin ELISA Standartisation. J.Autoimmunity, 2000,15,195-197</p><p>Решетняк T.M., Алекберова 3.C., ЕЛ.Насонов и соавт. Антитела к р2-гликопротеину I новый тип антифосфолипид- ных антител. Клин, мед., 1998, 3,36-40</p><p>Reutelingsperger СРМ. Annexins: Key regulators of haemostasis, thrombosis, and apoptosis. Thromb. Haemost., 2001, 86, 413-419</p><p>Lakos G., Kiss E., Regeczy N. et al. Antiprothrombin and antiannexin V antibodies imply risk of thrombosis in patients with systemic autoimmune disease. J.Rheumatol., 2000,27,924-929</p><p>Rand J.H. Antiphospholipid antibody - mediated disruption of the annexine V antithrombotic shield. A thrombogenic mechanism for antiphospholipid syndrome. J.Autoimmunity, 2000, 15, 107-111</p><p>Siaka C., Lambert М., Caron C. et al. Low prewalence of antiannexin V antibodies in antiphospholipid syndrome with fetal loss. RevMed.Interne, 1999,20,762-765</p><p>Haem G., Nicaise-Roland P., Palazzo E. et al. Antioxidized low- dcnsity-Iipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome. Lupus, 2001, 10,346-351</p><p>Gomez-Zumaquero J.M., Tinahones F.J., De Ramon E. et al. Association of biological markers of activity of systemic lupus erythematosus with levels of anti-oxidized low-density lipoprotein antibodies. Rheumatology (Oxford), 2004, 43 (4), 510-513</p><p>Romero F.L, Amengual O., Atsumi T. et al. Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti beta2-glycoprotein I antibodies but not with antibodies against oxodozed low-density lipoprotein. Br.J.Rheumatol.</p></div><br /><div><p>Wilson W.A., Gharavi А.Е., Koike Т. et al.International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthr. Rheum., 1999,42, 1309-1311</p><p>Asherson R.A, Cervera R. 'Primary', 'secondary' and other variants of the antiphospholipid syndrome. Lupus, 1994, 3, 293-298</p><p>Насонов Е.Л. Антифосфолипидный синдром. М.,Литгера, 2004,440с</p><p>Tsutsumi A, Matsuura Е., Ichikawa К., et al. Antibodies to beta2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus. Arthr. Rheum., 1996, 39,14661474</p><p>Balestrieri G., Tincani A., Spatola L. et al. Anti |32-glycoprotein I antibodies: a marker of antiphospholipid syndrome? Lupus, 1995, 4, 122-130</p><p>Le Tonqueze М., Salozhin K., Dueymes M.et al. Role of beta2- glycoprotein 1 in the antiphospholipid antibody binding to endothelial cells. Lupus, 1995, 4,179-186</p><p>de Groot P.G., Derksem R.H.W.M. Protein С pathway, antiphospholipid antibodies and thrombosis. Lupus, 1994, 3, 229-233</p><p>Roubey R.A. Immunology of the antiphospholipid antibody syndrome. Arthr. Rheum., 1996,39,1444-1454</p><p>Radulescu L., Stancu C., Antohe F. Antibodies against human oxidized low-density lipoprotein (LDL) as markers for human plasma modified lipipoproteins. Mcd.Sci.Monit., 2004, 10(7), 207-214</p><p>Tan E.M., Cohen A.S., Fries J.F et al.The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthr.Rheum., 1982, 25, 1271-1277</p><p>Александрова E.H., Насонов Е.Л., Ковалев В.Ю. Количественный иммуноферментный метод определения антител к кардиолипину в сыворотке крови. Клин, ревматол., 1995, 4 35-39</p><p>Brandt J.T., Triplett D.A., Aving В., Scharrer I. Criteria for the diagnosis of lupus anticoagulant: An update. Thromb. Haemost., 1995, 74, 1185-1190</p><p>Баркаган 3.C., Момот А.П. Основы диагностики нарушений гемостаза. Москва.”Ньюдиамед-АО", 1999,.215с</p><p>Harris E.N., Gharavi А.Е., Boey M.L. et al. Anticardiolipin antibodies: detection by radioimmunoassay and assotiation with thrombosis in systemic lupus erythematosus. Lancet,1983,2,1211-1214</p><p>Harris E.N., Gharavi A.E., Patel S.P., Hughes G.R.V. Anticardiolipin antibody testing. The need for standardization. Arthr. Rheum., 1987,30,835-836</p><p>Harris E.N., Gharavi A.E., Patel S.P., Hughes G.R.V. Evalution of the anticardiolipin antibody test: Report of standartization workshop held in April 1986. Clin.Expe.Immuno!., 1987,68,215222</p><p>Harris E.N., Pierangeli S., Birch D. Anticardiolipin VJel Workshop Report. Fifth International Symposium on Antiphospholipid antibodies. Am.J.Clin.Pathol., 1994,101,616624</p><p>Carreras L.O., Forastiero R.R., Martinuzzo M.E. Which are the best biological markers of the antiphospholipid syndrome? J.Autoimmunity, 2000,15,163-172</p><p>Coulam C.B., McIntyre J.A., Wagenknecht D., Rote N. Interlaboratories inconsistencies in detection of anticardiolipin antibodies. Lancet, 1990,335,865</p><p>Tincani A., Balestrieri G., Allegri F. et al. Overview on Anticardiolipin ELISA Standartisation. J.Autoimmunity, 2000,15,195-197</p><p>Решетняк T.M., Алекберова 3.C., ЕЛ.Насонов и соавт. Антитела к р2-гликопротеину I новый тип антифосфолипид- ных антител. Клин, мед., 1998, 3,36-40</p><p>Reutelingsperger СРМ. Annexins: Key regulators of haemostasis, thrombosis, and apoptosis. Thromb. Haemost., 2001, 86, 413-419</p><p>Lakos G., Kiss E., Regeczy N. et al. Antiprothrombin and antiannexin V antibodies imply risk of thrombosis in patients with systemic autoimmune disease. J.Rheumatol., 2000,27,924-929</p><p>Rand J.H. Antiphospholipid antibody - mediated disruption of the annexine V antithrombotic shield. A thrombogenic mechanism for antiphospholipid syndrome. J.Autoimmunity, 2000, 15, 107-111</p><p>Siaka C., Lambert М., Caron C. et al. Low prewalence of antiannexin V antibodies in antiphospholipid syndrome with fetal loss. RevMed.Interne, 1999,20,762-765</p><p>Haem G., Nicaise-Roland P., Palazzo E. et al. Antioxidized low- dcnsity-Iipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome. Lupus, 2001, 10,346-351</p><p>Gomez-Zumaquero J.M., Tinahones F.J., De Ramon E. et al. Association of biological markers of activity of systemic lupus erythematosus with levels of anti-oxidized low-density lipoprotein antibodies. Rheumatology (Oxford), 2004, 43 (4), 510-513</p><p>Romero F.L, Amengual O., Atsumi T. et al. Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti beta2-glycoprotein I antibodies but not with antibodies against oxodozed low-density lipoprotein. Br.J.Rheumatol.</p></div><br />

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