Preview

Rheumatology Science and Practice

Advanced search

Anti-topoisomerase 1 antibody level changes after B сell depletion therapy in systemic sclerosis

https://doi.org/10.47360/1995-4484-2022-57-63

Abstract

The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANA) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSc) patients on rituximab (RTX) therapy.
Materials and methods. The prospective study included 88 patients (73 women) with a mean age of 47 (17– 71) years. The mean disease duration was 5.9±4.8 years. The mean follow-up period was more than 2 years (27 (12–42) months).
Results. We documented a statistically significant change in skin score, the disease activity index, improvement of pulmonary function and reduction of mean dose of prednisolone after RTX treatment. There was a significant decrease in the number of patients with high levels of ANA and overall decrease of the ANA and anti-Topo 1 levels. A moderate positive statistically significant correlation was found between ANA and anti-Topo 1 (r=0.403). In the group of patients positive for anti-Topo 1 there were a more pronounced depletion of B lymphocytes, significantly higher increase in forced vital capacity and diffusion capacity, decrease in the disease activity index, compared with a patients negative for anti-Topo 1.
Conclusions. We observed the decline in the level of ANA and anti-Topo 1 in SSc patients after RTX therapy and it was correlated by an improvement of the main outcome parameters of the disease. Therefore, anti-Topo 1 positivity could be considered as a predictor of a better response to RTX treatment, especially in SSc patients with hyperproduction of anti-Topo 1.

About the Authors

L. P. Ananyeva
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Lidia Ananyeva

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



L. A. Garzanova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Lyudmila A. Garzanova

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



O. A. Koneva
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Olga A. Koneva

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



M. N. Starovoytova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Mayya N. Starovoytova

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



O. V. Desinova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Oxana V. Desinova

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



O. B. Ovsyannikova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Olga B. Ovsyannikova

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



R. U. Shayakhmetova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Rushana U. Shayakhmetova

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



M. V. Cherkasova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Mariya V. Cherkasova

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



A. P. Aleksankin
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Andrey P. Aleksankin

115522, Moscow, Kashirskoye Highway, 34A


Competing Interests:

нет



E. L. Nasonov
V.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russian Federation (Sechenov University)
Russian Federation

Evgeny L. Nasonov

115522, Moscow, Kashirskoye Highway, 34A

119991, Moscow, Trubetskaya str., 8, building 2


Competing Interests:

нет



References

1. Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685-1699. doi: 10.1016/S0140-6736(17)30933-9

2. Mehra S, Walker J, Patterson K, Fritzler MJ. Autoantibodies in systemic sclerosis. Autoimmun Rev. 2013;12(3):340-354. doi: 10.1016/j.autrev.2012.05.011

3. Ananyeva LP, Aleksandrova EN. Autoantibodies in systemic sclerosis: Spectrum, clinical associations, and prognostic value. Nauchcno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2016;54(1):86-99 (In Russ.). doi: 10.14412/1995-4484-2016-86-99

4. Bossuyt X, De Langhe E, Borghi MO, Meroni PL. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nat Rev Rheumatol. 2020;16(12):715-726. doi: 10.1038/s41584-020-00522-w

5. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: An American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737-2747. doi: 10.1002/art.38098

6. Tiniakou E, Crawford J, Darrah E. Insights into origins and specificities of autoantibodies in systemic sclerosis. Curr Opin Rheumatol. 2021;33(6):486-494. doi: 10.1097/BOR.0000000000000834

7. Nihtyanova SI, Denton CP. Autoantibodies as predictive tools in systemic sclerosis. Nat Rev Rheumatol. 2010;6(2):112-116. doi: 10.1038/nrrheum.2009.238

8. Nihtyanova SI, Sari A, Harvey JC, Leslie A, Derrett-Smith EC, Fonseca C, et al. Using autoantibodies and cutaneous subset to develop outcome-based disease classification in systemic sclerosis. Arthritis Rheumatol. 2020;72(3):465-476. doi: 10.1002/art.41153

9. Kuwana M, Gil-Vila A, Selva-O’Callaghan A. Role of autoantibodies in the diagnosis and prognosis of interstitial lung disease in autoimmune rheumatic disorders. Ther Adv Musculoskelet Dis. 2021;13:1759720X211032457. doi: 10.1177/1759720X211032457

10. Yoshizaki A. Pathogenic roles of B lymphocytes in systemic sclerosis. Immunol Lett. 2018;195:76-82. doi: 10.1016/j.imlet.2018.01.002

11. Melissaropoulos K, Daoussis D. B cells in systemic sclerosis: From pathophysiology to treatment. Clin Rheumatol. 2021;40(7):2621-2631. doi: 10.1007/s10067-021-05665-z

12. Burbelo PD, Iadarola MJ, Keller JM, Warner BM. Autoantibodies targeting intracellular and extracellular proteins in autoimmunity. Front Immunol. 2021;12:548469. doi: 10.3389/fimmu.2021.548469

13. Yoshizaki A, Yanaba K, Ogawa A, Asano Y, Kadono T, Sato S. Immunization with DNA topoisomerase I and Freund’s complete adjuvant induces skin and lung fibrosis and autoimmunity via interleukin-6 signaling. Arthritis Rheum. 2011;63(11):3575-3585. doi: 10.1002/art.30539

14. Mehta H, Goulet PO, Nguyen V, Pérez G, Koenig M, Senécal JL, et al. Topoisomerase I peptide-loaded dendritic cells induce autoantibody response as well as skin and lung fibrosis. Autoimmunity. 2016;49(8):503-513. doi: 10.1080/08916934.2016.1230848

15. Cottrell TR, Askin F, Halushka MK, Casciola-Rosen L, McMahan ZH. Expression of the autoantigen topoisomerase-1 is enriched in the lung tissues of patients with autoimmune interstitial lung disease: A case control study. ACR Open Rheumatol. 2020;2(11):657-661. doi: 10.1002/acr2.11191

16. Fava A, Cimbro R, Wigley FM, Liu QR, Rosen A, Boin F. Frequency of circulating topoisomerase-I-specific CD4 T cells predicts presence and progression of interstitial lung disease in scleroderma. Arthritis Res Ther. 2016;18(1):99. doi: 10.1186/s13075-016-0993-2

17. Kuwana M, Kaburaki J, Mimori T, Kawakami Y, Tojo T. Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis. Arthritis Rheum. 2000;43(5):1074-1084. doi: 10.1002/1529-0131(200005)43:5<1074::AIDANR18>3.0.CO;2-E

18. Einhaus J, Pecher AC, Asteriti E, Schmid H, Secker KA, DuerrStoerzer S, et al. Inhibition of effector B cells by ibrutinib in systemic sclerosis. Arthritis Res Ther. 2020;22(1):66. doi: 10.1186/s13075-020-02153-8

19. Hu PQ, Fertig N, Medsger TA Jr, Wright TM. Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. Arthritis Rheum. 2003;48(5):1363-1373. doi: 10.1002/art.10977

20. Sato S, Hamaguchi Y, Hasegawa M, Takehara K. Clinical significance of anti-topoisomerase I antibody levels determined by ELISA in systemic sclerosis. Rheumatology (Oxford). 2001;40(10):1135-1140. doi: 10.1093/rheumatology/40.10.1135

21. Henes J, Glaeser L, Kötter I, Vogel W, Kanz L, Klein R. Analysis of anti-topoisomerase I antibodies in patients with systemic sclerosis before and after autologous stem cell transplantation. Rheumatology (Oxford). 2017;56(3):451-456. doi: 10.1093/rheumatology/kew319

22. Nasonov EL (ed.). Anti-B cell therapy in rheumatology: Focus on rituximab. Moscow:IMA-PRESS;2012 (In Russ.).

23. Lee DSW, Rojas OL, Gommerman JL. B cell depletion therapies in autoimmune disease: Advances and mechanistic insights. Nat Rev Drug Discov. 2021;20(3):179-199. doi: 10.1038/s41573-020-00092-2

24. Nasonov EL, Beketova TV, Ananyeva LP, Vasilyev VI, Solovyev SK, Avdeeva AS. Prospects for anti-B cell therapy in immuno-inflammatory rheumatic diseases. NauchcnoPrakticheskaya Revmatologia = Rheumatology Science and Practice. 2019;57:1-40 (In Russ.). doi: 10.14412/1995-4484-2019-3-40

25. Ananieva LP, Desinova OV, Koneva OA, Starovoitova MN, Yutkina NN, Volkov AV, et al. Rituximab treatment for interstitial lung injury in scleroderma systematica. Nauchcno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2013;51(5):514-523 (In Russ.). doi: 10.14412/1995-4484-2013-1542

26. Ananyeva LP, Koneva OA, Desinova OV, Garzanova LA, Glukhova SI, Starovoitova MN, et al. Effect of rituximab on the manifestations of activity and pulmonary function in patients with systemic sclerosis: One-year follow-up evaluation. Nauchcno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2019;57(3):265-273 (In Russ.). doi: 10.14412/1995-4484-2019-265-273

27. M systemic sclerosis disease (SSc): Systematic review and metaanalysis. Clin Rheumatol. 2021;40(10):3897-3918. doi: 10.1007/s10067-021-05698-4

28. oradzadeh M, Aghaei M, Mehrbakhsh Z, Arab-Bafrani Z, Abdollahi N. Efficacy and safety of rituximab therapy in patients with Goswami RP, Ray A, Chatterjee M, Mukherjee A, Sircar G, Ghosh P. Rituximab in the treatment of systemic sclerosis-related interstitial lung disease: A systematic review and meta-analysis. Rheumatology (Oxford). 2021;60(2):557-567. doi: 10.1093/rheumatology/keaa550

29. de Figueiredo Caldas MMV, de Azevedo KPM, de França Nunes AC, de Oliveira VH, Pimenta IDSF, de Araújo IDT, et al. Is rituximab effective for systemic sclerosis? A systematic review and meta-analysis. Adv Rheumatol. 2021;61(1):15. doi: 10.1186/s42358-021-00170-y

30. Moazedi-Fuerst FC, Kielhauser SM, Hermann J, Meilinger M, Demel U, Stradner MH, et al. Decrease in autoantibody titres during long-term treatment of scleroderma with rituximab: A promising surveillance marker of therapy? Scand J Rheumatol. 2015;44(6):519-520. doi: 10.3109/03009742.2015.1069888

31. Bonroy C, Smith V, Deschepper E, De Keyser F, Devreese K. Specific antinuclear antibody level changes after B cell depletion therapy in systemic sclerosis are associated with improvement of skin thickening. J Rheumatol. 2016;43(1):247-249. doi: 10.3899/jrheum.150105

32. Ebata S, Yoshizaki A, Fukasawa T, Miura S, Takahashi T, Sumida H, et al. Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with antitopoisomerase I-positive systemic sclerosis-associated interstitial lung disease. J Dermatol. 2019;46(11):1006-1013. doi: 10.1111/1346-8138.15079

33. Fernández-Codina A, Walker KM, Pope JE; Scleroderma Algorithm Group. Treatment algorithms for systemic sclerosis according to experts. Arthritis Rheumatol. 2018;70(11):1820-1828. doi: 10.1002/art.40560

34. Valentini G, Della Rossa A, Bombardieri S, Bencivelli W, Silman AJ, D’Angelo S, et al. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis. 2001;60(6):592-598. doi: 10.1136/ard.60.6.592

35. Kahaleh MB, Sultany GL, Smith EA, Huffstutter JE, Loadholt CB, LeRoy EC. A modified scleroderma skin scoring method. Clin Exp Rheumatol. 1986;4(4):367-369.

36. Elhai M, Boubaya M, Distler O, Smith V, Matucci-Cerinic M, Alegre Sancho JJ, et al.; for EUSTAR network. Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: A prospective cohort study. Ann Rheum Dis. 2019;78(7):979-987. doi: 10.1136/annrheumdis-2018-214816

37. Hughes M, Denton CP, Khanna D. Rituximab for the treatment of systemic sclerosis-interstitial lung disease. Rheumatology (Oxford). 2021;60(2):489-491. doi: 10.1093/rheumatology/keaa675

38. Tang R, Yu J, Shi Y, Zou P, Zeng Z, Tang B, et al. Safety and efficacy of Rituximab in systemic sclerosis: A systematic review and meta-analysis. Int Immunopharmacol. 2020;83:106389. doi: 10.1016/j.intimp.2020.106389

39. Cambridge G, Leandro MJ, Teodorescu M, Manson J, Rahman A, Isenberg DA, et al. B cell depletion therapy in systemic lupus erythematosus: Effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum. 2006;54(11):3612-3622. doi: 10.1002/art.22211

40. Lazarus MN, Turner-Stokes T, Chavele KM, Isenberg DA, Ehrenstein MR. B-cell numbers and phenotype at clinical relapse following rituximab therapy differ in SLE patients according to anti-dsDNA antibody levels. Rheumatology (Oxford). 2012;51(7):1208-1215. doi: 10.1093/rheumatology/ker526

41. Tew GW, Rabbee N, Wolslegel K, Hsieh HJ, Monroe JG, Behrens TW, et al. Baseline autoantibody profiles predict normalization of complement and anti-dsDNA autoantibody levels following rituximab treatment in systemic lupus erythematosus. Lupus. 2010;19(2):146-157. doi: 10.1177/0961203309350752

42. Tsanian MÉ, Torgashina AV, Aleksandrova EN, Solov’ev SK, Nasonov EL. Anti-C1q antibodies in patients with systemic lupus erythematosus treated by rituximab. Terapevticheskii arkhiv. 2013;85(5):53-59 (In Russ.).

43. Cambridge G, Leandro MJ, Lahey LJ, Fairhead T, Robinson WH, Sokolove J. B cell depletion with rituximab in patients with rheumatoid arthritis: Multiplex bead array reveals the kinetics of IgG and IgA antibodies to citrullinated antigens. J Autoimmun. 2016;70:22-30. doi: 10.1016/j.jaut.2016.03.010

44. Modi S, Soejima M, Levesque MC. The effect of targeted rheumatoid arthritis therapies on anti-citrullinated protein autoantibody levels and B cell responses. Clin Exp Immunol. 2013;173(1):8-17. doi: 10.1111/cei.12114

45. Lindenberg L, Spengler L, Bang H, Dorner T, Maslyanskiy AL, Lapin SV, et al. Restrictive IgG antibody response against mutated citrullinated vimentin predicts response to rituximab in patients with rheumatoid arthritis. Arthritis Res Ther. 2015;17(1):206. doi: 10.1186/s13075-015-0717-z

46. Cortazar FB, Pendergraft WF 3rd, Wenger J, Owens CT, Laliberte K, Niles JL. Effect of continuous B cell depletion with rituximab on pathogenic autoantibodies and total IgG levels in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2017;69(5):1045-1053. doi: 10.1002/art.40032

47. van Dam LS, Dirikgil E, Bredewold EW, Ray A, Bakker JA, van Kooten C, et al. PR3-ANCAs predict relapses in ANCAassociated vasculitis patients after rituximab. Nephrol Dial Transplant. 2021;36(8):1408-1417. doi: 10.1093/ndt/gfaa066

48. Heitz M, Carron PL, Clavarino G, Jouve T, Pinel N, GuebreEgziabher F, et al. Use of rituximab as an induction therapy in anti-glomerular basement-membrane disease. BMC Nephrol. 2018;19(1):241. doi: 10.1186/s12882-018-1038-7

49. Uematsu-Uchida M, Ohira T, Tomita S, Satonaka H, Tojo A, Ishimitsu T. Rituximab in treatment of anti-GBM antibody glomerulonephritis: A case report and literature review. Medicine (Baltimore). 2019;98(44):e17801. doi: 10.1097/MD.0000000000017801

50. Beck LH Jr, Fervenza FC, Beck DM, Bonegio RG, Malik FA, Erickson SB, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol. 2011;22(8):1543-1550. doi: 10.1681/ASN.2010111125

51. Ruggenenti P, Debiec H, Ruggiero B, Chianca A, Pellé T, Gaspari F, et al. Anti-phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy. J Am Soc Nephrol. 2015;26(10):2545-2558. doi: 10.1681/ASN.2014070640

52. Arnold DM, Vrbensky JR, Karim N, Smith JW, Liu Y, Ivetic N, et al. The effect of rituximab on anti-platelet autoantibody levels in patients with immune thrombocytopenia. Br J Haematol. 2017;178(2):302-307. doi: 10.1111/bjh.14664

53. Dierickx D, Kentos A, Delannoy A. The role of rituximab in adults with warm antibody autoimmune hemolytic anemia. Blood. 2015;125(21):3223-3229. doi: 10.1182/blood-2015-01-588392

54. Yu L, Herold K, Krause-Steinrauf H, McGee PL, Bundy B, Pugliese A, et al.; Type 1 Diabetes TrialNet Anti-CD20 Study Group. Rituximab selectively suppresses specific islet antibodies. Diabetes. 2011;60(10):2560-2565. doi: 10.2337/db11-0674

55. Chatzidionysiou K, Lie E, Nasonov E, Lukina G, Hetland ML, Tarp U, et al. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: Pooled data from 10 European registries. Ann Rheum Dis. 2011;70(9):1575-1580. doi: 10.1136/ard.2010.148759

56. Isaacs JD, Cohen SB, Emery P, Tak PP, Wang J, Lei G, et al. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: A meta-analysis. Ann Rheum Dis. 2013;72(3):329-336. doi: 10.1136/annrheumdis-2011-201117

57. Porcelijn L, Huiskes E, Schipperus M, van der Holt B, de Haas M, Zwaginga JJ; Dutch HOVON 64 Study Group. Lack of detectable platelet autoantibodies is correlated with nonresponsiveness to rituximab treatment in ITP patients. Blood. 2017;129(25):3389-3391. doi: 10.1182/blood-2016-11-751719

58. Wang YM, Yu YF, Liu Y, Liu S, Hou M, Liu XG. The association between antinuclear antibody and response to rituximab treatment in adult patients with primary immune thrombocytopenia. Hematology. 2020;25(1):139-144. doi: 10.1080/16078454.2020.1740430

59. Crickx E, Weill JC, Reynaud CA, Mahévas M. Anti-CD20- mediated B-cell depletion in autoimmune diseases: Successes, failures and future perspectives. Kidney Int. 2020;97(5):885-893. doi: 10.1016/j.kint.2019.12.025

60. Boonstra M, Bakker JA, Grummels A, Ninaber MK, Ajmone Marsan N, Wortel CM, et al. Association of antitopoisomerase I antibodies of the IgM isotype with disease progression in anti-topoisomerase I-positive systemic sclerosis. Arthritis Rheumatol. 2020;72(11):1897-1904. doi: 10.1002/art.41403

61. Simon D, Balogh P, Erdő-Bonyár S, Böröcz K, Minier T, Czirják L, et al. Increased frequency of activated switched memory B cells and its association with the presence of pulmonary fibrosis in diffuse cutaneous systemic sclerosis patients. Front Immunol. 2021;12:686483. doi: 10.3389/fimmu.2021.686483

62. Leandro MJ. B-cell subpopulations in humans and their differential susceptibility to depletion with anti-CD20 monoclonal antibodies. Arthritis Res Ther. 2013;15(Suppl 1):S3. doi: 10.1186/ar3908

63. Wilk E, Witte T, Marquardt N, Horvath T, Kalippke K, Scholz K, et al. Depletion of functionally active CD20+ T cells by rituximab treatment. Arthritis Rheum. 2009;60(12):3563-3571. doi: 10.1002/art.24998. PMID: 19950291

64. Eggleton P, Bremer E, Tarr JM, de Bruyn M, Helfrich W, Kendall A, et al. Frequency of Th17 CD20+ cells in the peripheral blood of rheumatoid arthritis patients is higher compared to healthy subjects. Arthritis Res Ther. 2011;13(6):R208. doi: 10.1186/ar3541

65. van de Veerdonk FL, Lauwerys B, Marijnissen RJ, Timmermans K, Di Padova F, Koenders MI, et al. The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum. 2011;63(6):1507-1516. doi: 10.1002/art.30314

66. Kuwana M, Medsger TA Jr, Wright TM. Analysis of soluble and cell surface factors regulating anti-DNA topoisomerase I autoantibody production demonstrates synergy between Th1 and Th2 autoreactive T cells. J Immunol. 2000;164(12):6138-6146. doi: 10.4049/jimmunol.164.12.6138

67. Hasegawa M, Hamaguchi Y, Yanaba K, Bouaziz JD, Uchida J, Fujimoto M, et al. B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis. Am J Pathol. 2006;169(3):954-966. doi: 10.2353/ajpath.2006.060205

68. Bosello S, De Santis M, Lama G, Spanò C, Angelucci C, Tolusso B, et al. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther. 2010;12(2):R54. doi: 10.1186/ar2965

69. She YX, Yu QY, Tang XX. Role of interleukins in the pathogenesis of pulmonary fibrosis. Cell Death Discov. 2021;7(1):52. doi: 10.1038/s41420-021-00437-9

70. Ananyeva LP. Prospects for using tocilizumab in systemic sclerosis. NauchcnoPrakticheskaya Revmatologia = Rheumatology Science and Practice. 2015;53(6):632-640 (In Russ.). doi: 10.14412/1995-4484-2015-632-640

71. Shima Y. The benefits and prospects of interleukin-6 inhibitor on systemic sclerosis. Mod Rheumatol. 2019;29(2):294-301. doi: 10.1080/14397595.2018.1559909


Review

For citations:


Ananyeva L.P., Garzanova L.A., Koneva O.A., Starovoytova M.N., Desinova O.V., Ovsyannikova O.B., Shayakhmetova R.U., Cherkasova M.V., Aleksankin A.P., Nasonov E.L. Anti-topoisomerase 1 antibody level changes after B сell depletion therapy in systemic sclerosis. Rheumatology Science and Practice. 2022;60(1):57–63. (In Russ.) https://doi.org/10.47360/1995-4484-2022-57-63

Views: 521


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)