Anti-topoisomerase 1 Antibody Level Changes After B Cell Depletion Therapy in Systemic Sclerosis

Overview

Journal Dokl Biochem Biophys

Specialties Biochemistry
Biophysics

Date 2023 Oct 13

PMID 37833608

Authors

L P Ananyeva

L A Garzanova

O A Koneva

M N Starovoytova

O V Desinova

O B Ovsyannikova

R U Shayakhmetova

M V Cherkasova

A P Aleksankin

E L Nasonov

Affiliations

Soon will be listed here.

Abstract

The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANAs) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSs) patients on rituximab (RTX) therapy. 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). 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 patients negative for anti-Topo 1. 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.

Citing Articles

Autoantibodies in systemic sclerosis: From disease bystanders to pathogenic players.

Chepy A, Collet A, Launay D, Dubucquoi S, Sobanski V J Transl Autoimmun. 2025; 10:100272.

PMID: 39917316 PMC: 11799969. DOI: 10.1016/j.jtauto.2025.100272.

Quantification of autoantibodies using a luminescent profiling method in autoimmune interstitial lung disease.

Burbelo P, Huapaya J, Khavandgar Z, Beach M, Pinal-Fernandez I, Mammen A Front Immunol. 2024; 15:1462242.

PMID: 39524452 PMC: 11543486. DOI: 10.3389/fimmu.2024.1462242.

References

Wilk E, Witte T, Marquardt N, Horvath T, Kalippke K, Scholz K . Depletion of functionally active CD20+ T cells by rituximab treatment. Arthritis Rheum. 2009; 60(12):3563-71. DOI: 10.1002/art.24998. View

Fernandez-Codina A, Walker K, Pope J . Treatment Algorithms for Systemic Sclerosis According to Experts. Arthritis Rheumatol. 2018; 70(11):1820-1828. DOI: 10.1002/art.40560. View

Valentini G, Della Rossa A, Bombardieri S, Bencivelli W, Silman A, DAngelo S . 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):592-8. PMC: 1753669. DOI: 10.1136/ard.60.6.592. View

Boonstra M, Bakker J, Grummels A, Ninaber M, Ajmone Marsan N, Wortel C . Association of Anti-Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti-Topoisomerase I-Positive Systemic Sclerosis. Arthritis Rheumatol. 2020; 72(11):1897-1904. PMC: 7702063. DOI: 10.1002/art.41403. View

Moradzadeh M, Aghaei M, Mehrbakhsh Z, Arab-Bafrani Z, Abdollahi N . Efficacy and safety of rituximab therapy in patients with systemic sclerosis disease (SSc): systematic review and meta-analysis. Clin Rheumatol. 2021; 40(10):3897-3918. DOI: 10.1007/s10067-021-05698-4. View

Heitz M, Carron P, Clavarino G, Jouve T, Pinel N, Guebre-Egziabher F . Use of rituximab as an induction therapy in anti-glomerular basement-membrane disease. BMC Nephrol. 2018; 19(1):241. PMC: 6149204. DOI: 10.1186/s12882-018-1038-7. View

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):3575-85. DOI: 10.1002/art.30539. View

van de Veerdonk F, Lauwerys B, Marijnissen R, Timmermans K, Di Padova F, Koenders M . The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum. 2011; 63(6):1507-16. DOI: 10.1002/art.30314. View

Hu P, Fertig N, Medsger Jr T, Wright T . Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. Arthritis Rheum. 2003; 48(5):1363-73. DOI: 10.1002/art.10977. View

10.

Goswami R, 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). 2020; 60(2):557-567. DOI: 10.1093/rheumatology/keaa550. View

11.

Porcelijn L, Huiskes E, Schipperus M, van der Holt B, de Haas M, Zwaginga J . 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. View

12.

Crickx E, Weill J, Reynaud C, Mahevas 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. View

13.

Hughes M, Denton C, Khanna D . Rituximab for the treatment of systemic sclerosis-interstitial lung disease. Rheumatology (Oxford). 2020; 60(2):489-491. DOI: 10.1093/rheumatology/keaa675. View

14.

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

15.

Wang Y, Yu Y, Liu Y, Liu S, Hou M, Liu X . 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. View

16.

Burbelo P, Iadarola M, Keller J, Warner B . Autoantibodies Targeting Intracellular and Extracellular Proteins in Autoimmunity. Front Immunol. 2021; 12:548469. PMC: 7982651. DOI: 10.3389/fimmu.2021.548469. View

17.

Cottrell T, Askin F, Halushka M, Casciola-Rosen L, McMahan Z . 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. PMC: 7672300. DOI: 10.1002/acr2.11191. View

18.

Fava A, Cimbro R, Wigley F, Liu Q, 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. PMC: 4857293. DOI: 10.1186/s13075-016-0993-2. View

19.

Tew G, Rabbee N, Wolslegel K, Hsieh H, Monroe J, Behrens T . Baseline autoantibody profiles predict normalization of complement and anti-dsDNA autoantibody levels following rituximab treatment in systemic lupus erythematosus. Lupus. 2009; 19(2):146-57. DOI: 10.1177/0961203309350752. View

20.

Cambridge G, Leandro M, Lahey L, Fairhead T, Robinson W, 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. View