rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2020-48-54rsp-2843Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHСравнительная характеристика основных фенотипов системной склеродермииComparative characteristics of the main phenotypes of systemic sclerosisШаяхметоваР. У.ShayakhmetovaR. U.

Рушана Ульфатовна Шаяхметова

115522, Москва, Каширское шоссе, 34А

Rushana Shayakhmetova

34A, Kashirskoe Shosse, Moscow 115522

rushick@rambler.ruАнаньеваЛ. П.AnanyevaL. P.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

СтаровойтоваМ. Н.StarovoitovaM. N.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ДесиноваО. В.DesinovaO. V.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

КоневаО. А.KonevaO. A.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ОвсянниковаО. Б.OvsyannikovaO. B.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ГарзановаЛ. А.GarzanovaL. A.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ЧеркасоваМ. В.CherkasovaM. V.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

АлекперовР. Т.AlekperovR. T.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ФГБНУ Научноисследовательский институт ревматологии им. В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation2020200220205814854Copyright © Шаяхметова Р.У., Ананьева Л.П., Старовойтова М.Н., Десинова О.В., Конева О.А., Овсянникова О.Б., Гарзанова Л.А., Черкасова М.В., Алекперов Р.Т., 20202020Шаяхметова Р.У., Ананьева Л.П., Старовойтова М.Н., Десинова О.В., Конева О.А., Овсянникова О.Б., Гарзанова Л.А., Черкасова М.В., Алекперов Р.Т.Shayakhmetova R.U., Ananyeva L.P., Starovoitova M.N., Desinova O.V., Koneva O.A., Ovsyannikova O.B., Garzanova L.A., Cherkasova M.V., Alekperov R.T.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/2843

Различные клинико-иммунологические фенотипы системной склеродермии (ССД) различаются по частоте и выраженности проявлений заболевания, прогрессированию поражения внутренних органов и прогнозу. Частота выявления антител к рибонуклеопротеину (анти-ШРНП) при ССД колеблется от 5 до 30%. Они встречаются при различных ревматических заболеваниях (ССД, системной красной волчанке, ревматоидном артрите, полимиозите, синдроме Шегрена) и ассоциируются с более благоприятным течением, хорошим ответом на лечение (в частности, на глюкокортикоиды), хорошим прогнозом. При ССД клинико-лабораторные ассоциации анти-ШРНП изучены недостаточно.

Цель исследования — сравнить клинико-лабораторные и инструментальные данные у больных ССД, позитивных по анти-ШРНП, антителам к топоизомеразе-I (анти-8е170) и антицентромерным антителам (АЦА).

Материал и методы

Материал и методы. Из общей базы данных больных, удовлетворяющих критериям ССД (ACR/EULAR 2013), наблюдаемых в ФГБНУ НИИР им. В.А. Насоновой в период с 2012 по 2017 г., в основную группу было отобрано 65 пациентов, позитивных по анти-ШРНП (I группа). В группы сравнения были включены 50 больных ССД, позитивных по анти-8е170 (II группа), и 50 пациентов, позитивных по АЦА (III группа). У больных групп сравнения была подтверждена негативность по анти-ШРНП.

Результаты и обсуждение

Результаты и обсуждение. У большинства больных I и III групп были лимитированная форма (88 и 94%) и хроническое течение заболевания (82 и 94% соответственно), в то время как для больных II группы было характерно острое и подострое течение (52%) и у них преобладала диффузная форма заболевания (58%). Все больные ССД имели повышение уровня антинуклеарного фактора. Особенностью группы, позитивной по анти-ШРНП, явилось преобладание лимитированной формы заболевания с минимальным поражением кожи, в сочетании с более частым вовлечением костно-мышечной системы (поражение суставов у 65% и мышц у 43% больных), а также высокой частотой поражения внутренних органов (в частности, легких, сердца и желудочно-кишечного тракта). Для больных этой группы были характерны высокая воспалительная и иммунологическая активность, гематологические нарушения (гипокомплементемия у 15% и лейкопения у 14%). Синдром Шегрена выявлен у трети из этих больных.

Заключение

Заключение. Дальнейшее изучение позитивного по анти-ШРНП варианта ССД позволит составить алгоритм ведения и более четко определить риски и прогноз заболевания для данной группы больных.

Various clinical and immunological phenotypes of systemic sclerosis (SS) differ in the frequency and severity of manifestations of the disease, the progression of damage to internal organs, and prognosis. The detection rate of anti-U1-ribonucleoprotein (RNP) (anti-U1RNP) antibodies in SSD ranges from 5 to 30%. They are found in various rheumatic diseases (SS, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, and Sjo gren’s syndrome) and are associated with a more favorable course, a good response to treatment (in particular, that with glucocorticoids), and a good prognosis. In SS, the clinical and laboratory associations of anti-U1RNP have been insufficiently investigated.

Objective

Objective: to compare clinical, laboratory, and instrumental findings in patients with SS positive for anti-U1RNP, anti-topoisomerase-I (anti-Scl70), and anticentromere antibodies (ACA).

Subjects and methods

Subjects and methods. Sixty-five anti-U1RNP antibody-positive patients were selected for a study group (Group 1) from the general database of patients who met the 2013 ACR/EULAR criteria for SS and who were followed up at the V.A. Nasonova Research Institute of Rheumatology in 2012 to 2017. The comparison groups included 50 anti-Scl70 antibody-positive patients with SS (Group 2) and 50 ACA-positive ones (Group 3). Anti-U1RNP negativity was confirmed in patients of the comparison groups.

Results and discussion

Results and discussion. Most patients in Groups 1 and 3 had the limited type of SS (88 and 94%, respectively) and a chronic course of the disease (82 and 94%) while Group 2 patients showed an acute and subacute course (52%) and predominantly the diffuse type of SS (58%). All the patients with SS had a higher level of antinuclear factor. The feature of the anti-U1RNP positive group was a preponderance of the limited type of the disease with minimal skin damage concurrent with a more frequent involvement of the musculoskeletal system (damages to the joints (65%) and muscles (43%), as well as with the high rate of damage to internal organs (in particular, the lung, heart, and gastrointestinal tract). The patients of this group exhibited high inflammatory and immunological activities, hematological disorders (hypocomplementemia (15%) and leukopenia (14%)). Sjo gren’s syndrome was detected in one-third of these patients.

Conclusion

Conclusion. Further study of anti-U1RNP-positive SS will be able to create a management algorithm and to more clearly define the risks and prognosis of the disease for this group of patients.

системая склеродермияанти-ШРНПаутоантителафенотипыsystemic sclerosisanti-U1RNPautoantibodiesphenotypesReferencesГусева НГ. Системная склеродермия и псевдосклеродерми-ческие синдромы. Москва: Медицина; 1993 [Guseva NG. Sistemnaya sklerodermiya i psevdosklerodermicheskie sindromyGuseva NG. Sistemnaya sklerodermiya i psevdosklerodermicheskie sindromy [Systemic scleroderma and pseudoscleroderma syndromes]. Moscow: Meditsina; 1993 (In Russ.).Hamaguchi Y. Autoantibody profiles in systemic sclerosis: Predictive value for clinical evaluation and prognosis. J Dermatol. 2010;37:42-53. doi: 10.1111/j.1346-8138.2009.00762.xHamaguchi Y. Autoantibody profiles in systemic sclerosis: Predictive value for clinical evaluation and prognosis. J Dermatol. 2010;37:42-53. doi: 10.1111/j.1346-8138.2009.00762.xСтаровойтова МН, Десинова ОВ, Конева ОА и др. Профиль аутоантител при системной склеродермии. Научно-практическая ревматология. 2016;54(4):418-23. doi: 10.14412/1995-4484-2016-418-423Starovoitova MN, Desinova OV, Koneva OA, et al. Profile of autoantibodies in systemic sclerosis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(4):418-23 (In Russ.). doi: 10.14412/1995-4484-2016-418-423Александрова ЕН, Новиков АА, Насонов ЕЛ. Современные подходы к лабораторной диагностике ревматических заболеваний: роль молекулярных и клеточных биомаркеров. Научно-практическая ревматология. 2016;54(3):324-38. doi: 10.14412/1995-4484-2016-324-338Aleksandrova EN, Novikov AA, Nasonov EL. Current approaches to the laboratory diagnosis of rheumatic diseases: Role of molecular and cellular biomarkers. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(3):324-38 (In Russ.). doi: 10.14412/1995-4484-2016-324-338Ананьева ЛП, Александрова ЕН. Аутоантитела при системной склеродермии: спектр, клинические ассоциации и прогностическое значение. Научно-практическая ревматология. 2016;54(1):86-99. doi: 10.14412/1995-4484-2016-86-99Ananyeva LP, Aleksandrova EN. Autoantibodies in scleroderma systematica: Spectrum, clinical associations, and prognostic value. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(1):86-99 (In Russ.). doi: 10.14412/1995-4484-2016-86-99Kuwana M. Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting. J Nippon MedSch. 2017;84(2):56-63. doi: 10.1272/jnms.84.56Kuwana M. Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting. J Nippon MedSch. 2017;84(2):56-63. doi: 10.1272/jnms.84.56Hesselstrand R, Scheja A, Shen GQ, et al. The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis. Rheumatology (Oxford). 2003;42:534-40. doi: 10.1093/rheumatology/keg170Hesselstrand R, Scheja A, Shen GQ, et al. The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis. Rheumatology (Oxford). 2003;42:534-40. doi: 10.1093/rheumatology/keg170Hamaguchi Y, Kodera M, Matsushita T, et al. Clinical and immunological predictors of scleroderma renal crisis for Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies. Arthritis Rheum. 2015;67:1045-52. doi: 10.1002/art.38994Hamaguchi Y, Kodera M, Matsushita T, et al. Clinical and immunological predictors of scleroderma renal crisis for Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies. Arthritis Rheum. 2015;67:1045-52. doi: 10.1002/art.38994Moinzadeh P, Fonseca C, Hellmich M, et al. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Res Ther. 2014;16:R53. doi: 10.1186/ar4486Moinzadeh P, Fonseca C, Hellmich M, et al. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Res Ther. 2014;16:R53. doi: 10.1186/ar4486Jung M, Baron M, Hudson M, et al. Myopathy is a poor prognostic feature in systemic sclerosis: results from the Canadian Scleroderma Research Group (CSRG) cohort. Scand J Rheumatol. 2014;43(3):217-20. doi: 10.3109/03009742.2013.868512Jung M, Baron M, Hudson M, et al. Myopathy is a poor prognostic feature in systemic sclerosis: results from the Canadian Scleroderma Research Group (CSRG) cohort. Scand J Rheumatol. 2014;43(3):217-20. doi: 10.3109/03009742.2013.868512Hoffmann AM, Gunnarsson R, Garen T, et al. Performance of the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis (SSc) in Large, Well-defined Cohorts of SSc and Mixed Connective Tissue Disease. J Rheumatol. 2015;42:60-3. doi: 10.3899/jrheum.140047Hoffmann AM, Gunnarsson R, Garen T, et al. Performance of the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis (SSc) in Large, Well-defined Cohorts of SSc and Mixed Connective Tissue Disease. J Rheumatol. 2015;42:60-3. doi: 10.3899/jrheum.140047Hamaguchi Y, Hasegawa M, Fujimoto M, et al. The clinical relevance of serum antinuclear antibodies in Japanese patients with systemic sclerosis. Br J Dermatol. 2008;158(3):487-95. doi: 10.1111/j.1365-2133.2007.08392.xHamaguchi Y, Hasegawa M, Fujimoto M, et al. The clinical relevance of serum antinuclear antibodies in Japanese patients with systemic sclerosis. Br J Dermatol. 2008;158(3):487-95. doi: 10.1111/j.1365-2133.2007.08392.xSteen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005;35:35-42. doi: 10.1016/j.semarthrit.2005.03.005Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005;35:35-42. doi: 10.1016/j.semarthrit.2005.03.005Reveille JD, Fischbach M, McNearney T, et al. Systemic sclerosis in 3 US ethnic groups: a comparison of clinical sociodemographic, serologic, and immunogenetic determinants. Semin Arthritis Rheum. 2001;30:332-46. doi: 10.1053/sarh.2001.20268Reveille JD, Fischbach M, McNearney T, et al. Systemic sclerosis in 3 US ethnic groups: a comparison of clinical sociodemographic, serologic, and immunogenetic determinants. Semin Arthritis Rheum. 2001;30:332-46. doi: 10.1053/sarh.2001.20268Kuwana M, Kaburaki J, Okano Y, et al. Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis. Arthritis Rheum. 1994;37:75-83. doi: 10.1002/art.1780370111Kuwana M, Kaburaki J, Okano Y, et al. Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis. Arthritis Rheum. 1994;37:75-83. doi: 10.1002/art.1780370111Шаяхметова РУ, Ананьева ЛП, Конева ОА и др. Клинико-лабораторная характеристика больных системной склеродермией позитивных по антителам к рибонуклеопротеину. Научно-практическая ревматология. 2019;57(5):539-44. doi: 10.14412/1995-4484-2019-539-544Shayakhmetova RU, Ananyeva LP, Koneva OA, et al. Clinical and laboratory characteristics of patients with systemic sclerosis positive for anti-ribonucleoprotein antibodies. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2019;57(5):539-44 (In Russ.). doi: 10.14412/1995-4484-2019-539-544Carpintero MF, Martinez L, Fernandez I, et al. Diagnosis and risk stratification in patients with anti-RNP autoimmunity. Lupus. 2015;24(10):1057-66. doi: 10.1177/0961203315575586Carpintero MF, Martinez L, Fernandez I, et al. Diagnosis and risk stratification in patients with anti-RNP autoimmunity. Lupus. 2015;24(10):1057-66. doi: 10.1177/0961203315575586Brahms H, Raker VA, van Venrooij WJ, et al. A major, novel systemic lupus erythematosus autoantibody class recognizes the E, F, and G SmsnRNP proteins as an E—F—G complex but not in their denatured states. Arthritis Rheum. 1997;40:672-82. doi: 10.1002/art.1780400412Brahms H, Raker VA, van Venrooij WJ, et al. A major, novel systemic lupus erythematosus autoantibody class recognizes the E, F, and G SmsnRNP proteins as an E—F—G complex but not in their denatured states. Arthritis Rheum. 1997;40:672-82. doi: 10.1002/art.1780400412Lokesh S, Kadavanu T, Raghupathy, et al. A Rare Case of Mixed Connective Tissue Disease (MCTD) with Intricate Features of Lupus, Polymyositis and Rheumatoid Arthritis Presenting with Severe Myositis. J Clin Diagn Res. 2015;9(3):5-7.Lokesh S, Kadavanu T, Raghupathy, et al. A Rare Case of Mixed Connective Tissue Disease (MCTD) with Intricate Features of Lupus, Polymyositis and Rheumatoid Arthritis Presenting with Severe Myositis. J Clin Diagn Res. 2015;9(3):5-7.Десинова ОВ, Старовойтова МН, Гусева ИА и др. Особенности перекрестной формы системной склеродермии с ревматоидным артритом (ССД-РА overlap-синдром). Научно-практическая ревматология. 2007;45(4):18-23. doi: 10.14412/1995-4484-2007-18-23Desinova OV, Starovoytova MN, Guseva IA, et al. Features of systemic sclerosis-rheumatoid arthritis overlap syndrome (SS-RA overlap syndrome). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2007;45(4):18-23 (In Russ.). doi: 10.14412/1995-4484-2007-18-23Brennan P, Silman A, Black C and the UK Scleroderma Study Group. Realiability of skin score measures in scleroderma. Br J Rheumatol. 1992;31:457-60. doi: 10.1093/rheumatology/31.7.457Brennan P, Silman A, Black C and the UK Scleroderma Study Group. Realiability of skin score measures in scleroderma. Br J Rheumatol. 1992;31:457-60. doi: 10.1093/rheumatology/31.7.457Насонов ЕЛ, редактор. Российские клинические рекомендации. Ревматология. Москва: ГЭОТАР-Медиа; 2017. С. 150-66 [Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya. ISBN 978-5-9704-4261-6Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya [Russian clinical recommendations. Rheumatology]. Moscow: GEOTAR-Media; 2017. P. 150-66 (In Russ.). ISBN 978-5-9704-4261-6Hamaguchi Y, Takehara K. Anti-nuclear autoantibodies in systemic sclerosis?: News and perspectives. J Scler Relat Disord. 2018;3(3):201-13. doi: 10.1177/2397198318783930Hamaguchi Y, Takehara K. Anti-nuclear autoantibodies in systemic sclerosis?: News and perspectives. J Scler Relat Disord. 2018;3(3):201-13. doi: 10.1177/2397198318783930Steen V, Domsic RT, Lucas M, et al. A clinical and serologic comparison of African American and Caucasian patients with systemic sclerosis. Arthritis Rheum. 2012;64(9): 2986-994. doi: 10.1002/art.34482Steen V, Domsic RT, Lucas M, et al. A clinical and serologic comparison of African American and Caucasian patients with systemic sclerosis. Arthritis Rheum. 2012;64(9): 2986-994. doi: 10.1002/art.34482Ihn H, Yamane K, Yazawa N, et al. Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis. Clin Exp Immunol. 1999;117(2):383-7. doi: 10.1046/j.1365-2249.1999.00961.xIhn H, Yamane K, Yazawa N, et al. Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis. Clin Exp Immunol. 1999;117(2):383-7. doi: 10.1046/j.1365-2249.1999.00961.xSobanski V, Giovannelli J, Lynch BM. Characteristics and survival of anti-U1 RNP antibody-positive patients with connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheum. 2016;68:484-93. doi: 10.1002/art.39432Sobanski V, Giovannelli J, Lynch BM. Characteristics and survival of anti-U1 RNP antibody-positive patients with connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheum. 2016;68:484-93. doi: 10.1002/art.39432Lundberg I, Hedfors E. Clinical course of patients with anti-RNP antibodies. A prospective study of 32 patients. J Rheumatol. 1991;18:1511-9.Lundberg I, Hedfors E. Clinical course of patients with anti-RNP antibodies. A prospective study of 32 patients. J Rheumatol. 1991;18:1511-9.Baldini С, Mosca M, Della Rossa A, et al. Overlap of ACA-posi-tive systemic sclerosis and Sjo gren’s syndrome: a distinct clinical entity with mild organ involvement but at high risk of lymphoma. Clin Exper Rheumatol. 2013;31:272-80.Baldini С, Mosca M, Della Rossa A, et al. Overlap of ACA-posi-tive systemic sclerosis and Sjo gren’s syndrome: a distinct clinical entity with mild organ involvement but at high risk of lymphoma. Clin Exper Rheumatol. 2013;31:272-80.

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