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. AnanyevaRussian Federation
Lidia Ananyeva
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
L. A. Garzanova
Russian Federation
Lyudmila A. Garzanova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
O. A. Koneva
Russian Federation
Olga A. Koneva
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
M. N. Starovoytova
Russian Federation
Mayya N. Starovoytova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
O. V. Desinova
Russian Federation
Oxana V. Desinova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
O. B. Ovsyannikova
Russian Federation
Olga B. Ovsyannikova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
R. U. Shayakhmetova
Russian Federation
Rushana U. Shayakhmetova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
M. V. Cherkasova
Russian Federation
Mariya V. Cherkasova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
A. P. Aleksankin
Russian Federation
Andrey P. Aleksankin
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
нет
E. L. Nasonov
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