nach oben

Clinical Rheumatology

Erschienen in:

21.03.2021 | Review Article

B cells in systemic sclerosis: from pathophysiology to treatment

verfasst von: Konstantinos Melissaropoulos, Dimitrios Daoussis

Erschienen in: Clinical Rheumatology | Ausgabe 7/2021

Einloggen, um Zugang zu erhalten

Abstract

Systemic sclerosis is a debilitating autoimmune disease with unknown pathogenesis. The clinical phenotype of fibrosis is preceded by vascular and immunologic aberrations. Adaptive immunity has been extensively studied in patients with the disease and B cells appear to be dysregulated. This is evident in peripheral blood B cell subsets, with activated effector B cells and impaired B regulatory function. In addition, B cells infiltrate target organs and tissues of patients with the disease, such as the skin and the lung, indicating a probable role in the pathogenesis. Impaired B cell homeostasis explains the rationale behind B cell therapeutic targeting. Indeed, several studies in recent years have shown that depletion of B cells appears to be a promising treatment alongside current established therapeutic choices, such as mycophenolate. In this review, B cell aberrations in animal models and human patients with systemic sclerosis will be presented. Moreover, we will also summarize current existing data regarding therapeutic targeting of the B cells in systemic sclerosis.

Elhai M, Meune C, Avouac J, Kahan A, Allanore Y (2012) Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology 51:1017–1026. https://doi.org/10.1093/rheumatology/ker269CrossRefPubMed

Gabrielli A, Avvedimento EV, Krieg T (2009) Scleroderma. N Engl J Med 360:1989–2003. https://doi.org/10.1056/NEJMra0806188CrossRefPubMed

Denton CP, Khanna D (2017) Systemic sclerosis. Lancet 390:1685–1699. https://doi.org/10.1016/S0140-6736(17)30933-9CrossRefPubMed

Brown M, O’Reilly S (2018) The immunopathogenesis of fibrosis in systemic sclerosis. Clin Exp Immunol. https://doi.org/10.1111/cei.13238

van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Müller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE (2013) 2013 Classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative: ACR/EULAR Classification Criteria for SSc. Arthritis Rheum 65:2737–2747. https://doi.org/10.1002/art.38098CrossRefPubMedPubMedCentral

Mehra S, Walker J, Patterson K, Fritzler MJ (2013) Autoantibodies in systemic sclerosis. Autoimmun Rev 12:340–354. https://doi.org/10.1016/j.autrev.2012.05.011CrossRefPubMed

Sakkas LI, Xu B, Artlett CM, Lu S, Jimenez SA, Platsoucas CD (2002) Oligoclonal T cell expansion in the skin of patients with systemic sclerosis. J Immunol 168:3649–3659. https://doi.org/10.4049/jimmunol.168.7.3649CrossRefPubMed

Eibel H, Kraus H, Sic H, Kienzler AK, Rizzi M (2014) B cell biology: an overview. Curr Allergy Asthma Rep 14:434. https://doi.org/10.1007/s11882-014-0434-8CrossRefPubMed

Baumgarth N (2011) The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat Rev Immunol 11:34–46. https://doi.org/10.1038/nri2901CrossRefPubMed

10.

Allman D, Pillai S (2008) Peripheral B cell subsets. Curr Opin Immunol 20:149–157. https://doi.org/10.1016/j.coi.2008.03.014CrossRefPubMedPubMedCentral

11.

Rosser EC, Mauri C (2015) Regulatory B cells: origin, phenotype, and function. Immunity 42:607–612. https://doi.org/10.1016/j.immuni.2015.04.005CrossRefPubMed

12.

Dalporto J (2004) B cell antigen receptor signaling 101. Mol Immunol 41:599–613. https://doi.org/10.1016/j.molimm.2004.04.008CrossRef

13.

Harwood NE, Batista FD (2008) New insights into the early molecular events underlying B cell activation. Immunity 28:609–619. https://doi.org/10.1016/j.immuni.2008.04.007CrossRefPubMed

14.

Kurosaki T (2011) Regulation of BCR signaling. Mol Immunol 48:1287–1291. https://doi.org/10.1016/j.molimm.2010.12.007CrossRefPubMed

15.

Tedder TF, Sato S, Poe JC, Fujimoto M (2000) CD19 and CD22 regulate a B lymphocyte signal transduction pathway that contributes to autoimmunity. Keio J Med 49:1–13. https://doi.org/10.2302/kjm.49.1CrossRefPubMed

16.

Doody GM, Dempsey PW, Fearon DT (1996) Activation of B lymphocytes: integrating signals from CD19, CD22 and FcγRIIb1. Curr Opin Immunol 8:378–382. https://doi.org/10.1016/S0952-7915(96)80128-2CrossRefPubMed

17.

Whitmire JK, Asano MS, Kaech SM, Sarkar S, Hannum LG, Shlomchik MJ, Ahmed R (2009) Requirement of B cells for generating CD4+ T cell memory. J Immunol 182:1868–1876. https://doi.org/10.4049/jimmunol.0802501CrossRefPubMedPubMedCentral

18.

Mackay F, Schneider P, Rennert P, Browning J (2003) BAFF and APRIL: a tutorial on B cell survival. Annu Rev Immunol 21:231–264. https://doi.org/10.1146/annurev.immunol.21.120601.141152CrossRefPubMed

19.

Wardemann H, Yurasov S, Schaefer A et al (2003) Predominant autoantibody production by early human B cell precursors. Sci New Ser 301:1374–1377

20.

Pillai S, Mattoo H, Cariappa A (2011) B cells and autoimmunity. Curr Opin Immunol 23:721–731. https://doi.org/10.1016/j.coi.2011.10.007CrossRefPubMedPubMedCentral

21.

Platt JL, Garcia de Mattos Barbosa M, Cascalho M (2019) The five dimensions of B cell tolerance. Immunol Rev 292:180–193. https://doi.org/10.1111/imr.12813CrossRefPubMed

22.

Asano Y, Sato S (2013) Animal models of scleroderma: current state and recent development. Curr Rheumatol Rep 15. https://doi.org/10.1007/s11926-013-0382-7

23.

Marangoni RG, Varga J, Tourtellotte WG (2016) Animal models of scleroderma: recent progress. Curr Opin Rheumatol 28:561–570. https://doi.org/10.1097/BOR.0000000000000331CrossRefPubMed

24.

Maurer B, Distler JHW, Distler O (2013) The Fra-2 transgenic mouse model of systemic sclerosis. Vasc Pharmacol 58:194–201. https://doi.org/10.1016/j.vph.2012.12.001CrossRef

25.

Saito S, Kasturi K, Bona C (1999) Genetic and immunologic features associated with scleroderma-like syndrome of TSK mice. Curr Rheumatol Rep 1:34–37CrossRef

26.

Long KB, Artlett CM, Blankenhorn EP (2014) Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis. Matrix Biol 38:91–100. https://doi.org/10.1016/j.matbio.2014.05.002CrossRefPubMed

27.

Phelps RG, Daian C, Shibata S, Fleischmajer R, Bona CA (1993) Induction of skin fibrosis and autoantibodies by infusion of immunocompetent cells from tight skin mice into C57BL/6 Pa/Pa mice. J Autoimmun 6:701–718. https://doi.org/10.1006/jaut.1993.1059CrossRefPubMed

28.

Sato S, Hasegawa M, Fujimoto M et al (2000) Quantitative genetic variation in CD19 expression correlates with autoimmunity. J Immunol 165:6635–6643. https://doi.org/10.4049/jimmunol.165.11.6635CrossRefPubMed

29.

Saito E, Fujimoto M, Hasegawa M et al (2002) CD19-Dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. J Clin Invest 109:1453–1462. https://doi.org/10.1172/JCI200215078CrossRefPubMedPubMedCentral

30.

Asano N, Fujimoto M, Yazawa N, Shirasawa S, Hasegawa M, Okochi H, Tamaki K, Tedder TF, Sato S (2004) B lymphocyte signaling established by the CD19/CD22 loop regulates autoimmunity in the tight-skin mouse. Am J Pathol 165:641–650. https://doi.org/10.1016/S0002-9440(10)63328-7CrossRefPubMedPubMedCentral

31.

Odaka M, Hasegawa M, Hamaguchi Y et al (2010) Autoantibody-mediated regulation of B cell responses by functional anti-CD22 autoantibodies in patients with systemic sclerosis. Clin Exp Immunol 159:176–184. https://doi.org/10.1111/j.1365-2249.2009.04059.xCrossRefPubMedPubMedCentral

32.

Hasegawa M, Hamaguchi Y, Yanaba K, Bouaziz JD, Uchida J, Fujimoto M, Matsushita T, Matsushita Y, Horikawa M, Komura K, Takehara K, Sato S, Tedder TF (2006) B-Lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis. Am J Pathol 169:954–966. https://doi.org/10.2353/ajpath.2006.060205CrossRefPubMedPubMedCentral

33.

Matsushita T, Fujimoto M, Hasegawa M, Matsushita Y, Komura K, Ogawa F, Watanabe R, Takehara K, Sato S (2007) BAFF antagonist attenuates the development of skin fibrosis in tight-skin mice. J Invest Dermatol 127:2772–2780. https://doi.org/10.1038/sj.jid.5700919CrossRefPubMed

34.

Yamamoto T, Takagawa S, Katayama I, Yamazaki K, Hamazaki Y, Shinkai H, Nishioka K (1999) Animal model of sclerotic skin. I: local injections of bleomycin induce sclerotic skin mimicking scleroderma. J Invest Dermatol 112:456–462. https://doi.org/10.1046/j.1523-1747.1999.00528.xCrossRefPubMed

35.

Yoshizaki A, Iwata Y, Komura K, Ogawa F, Hara T, Muroi E, Takenaka M, Shimizu K, Hasegawa M, Fujimoto M, Tedder TF, Sato S (2008) CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin-induced scleroderma. Am J Pathol 172:1650–1663. https://doi.org/10.2353/ajpath.2008.071049CrossRefPubMedPubMedCentral

36.

Komura K, Yanaba K, Horikawa M, Ogawa F, Fujimoto M, Tedder TF, Sato S (2008) CD19 regulates the development of bleomycin-induced pulmonary fibrosis in a mouse model. Arthritis Rheum 58:3574–3584. https://doi.org/10.1002/art.23995CrossRefPubMed

37.

Matsushita T, Kobayashi T, Mizumaki K et al (2018) BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance. Sci Adv 4:eaas9944. https://doi.org/10.1126/sciadv.aas9944CrossRefPubMedPubMedCentral

38.

Sanges S, Jendoubi M, Kavian N, Hauspie C, Speca S, Crave JC, Guerrier T, Lefèvre G, Sobanski V, Savina A, Hachulla E, Hatron PY, Labalette M, Batteux F, Dubucquoi S, Launay D (2017) B cell homeostasis and functional properties are altered in an hypochlorous acid-induced murine model of systemic sclerosis. Front Immunol 8:8. https://doi.org/10.3389/fimmu.2017.00053CrossRef

39.

Zhao C, Matsushita T, Ha Nguyen VT, Tennichi M, Fujimoto M, Takehara K, Hamaguchi Y (2020) CD22 and CD72 contribute to the development of scleroderma in a murine model. J Dermatol Sci 97:66–76. https://doi.org/10.1016/j.jdermsci.2019.12.007CrossRefPubMed

40.

Sato S, Fujimoto M, Hasegawa M, Takehara K (2004) Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum 50:1918–1927. https://doi.org/10.1002/art.20274CrossRefPubMed

41.

Soto L, Ferrier A, Aravena O et al (2015) Systemic sclerosis patients present alterations in the expression of molecules involved in B-cell regulation. Front Immunol. https://doi.org/10.3389/fimmu.2015.00496

42.

Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari CG, Bogdanos DP, Sakkas LI (2016) Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis: BREG CELLS IN SYSTEMIC SCLEROSIS. Arthritis Rheum 68:494–504. https://doi.org/10.1002/art.39437CrossRef

43.

Forestier A, Guerrier T, Jouvray M, Giovannelli J, Lefèvre G, Sobanski V, Hauspie C, Hachulla E, Hatron PY, Zéphir H, Vermersch P, Labalette M, Launay D, Dubucquoi S (2018) Altered B lymphocyte homeostasis and functions in systemic sclerosis. Autoimmun Rev 17:244–255. https://doi.org/10.1016/j.autrev.2017.10.015CrossRefPubMed

44.

Taher TE, Ong VH, Bystrom J, Hillion S, Simon Q, Denton CP, Pers JO, Abraham DJ, Mageed RA (2018) Association of defective regulation of autoreactive interleukin-6-producing transitional B lymphocytes with disease in patients with systemic sclerosis. Arthritis Rheum 70:450–461. https://doi.org/10.1002/art.40390CrossRef

45.

Matsushita T, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M (2016) Decreased levels of regulatory B cells in patients with systemic sclerosis: association with autoantibody production and disease activity. Rheumatology 55:263–267. https://doi.org/10.1093/rheumatology/kev331CrossRefPubMed

46.

Dumoitier N, Chaigne B, Régent A, Lofek S, Mhibik M, Dorfmüller P, Terrier B, London J, Bérezné A, Tamas N, Varin-Blank N, Mouthon L (2017) Scleroderma peripheral B lymphocytes secrete interleukin-6 and transforming growth factor β and activate fibroblasts. Arthritis Rheum 69:1078–1089. https://doi.org/10.1002/art.40016CrossRef

47.

Matsushita T, Hasegawa M, Yanaba K, Kodera M, Takehara K, Sato S (2006) Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes. Arthritis Rheum 54:192–201. https://doi.org/10.1002/art.21526CrossRefPubMed

48.

Matsushita T, Fujimoto M, Hasegawa M, Tanaka C, Kumada S, Ogawa F, Takehara K, Sato S (2007) Elevated serum APRIL levels in patients with systemic sclerosis: distinct profiles of systemic sclerosis categorized by APRIL and BAFF. J Rheumatol 34:2056–2062PubMed

49.

Bielecki M, Kowal K, Lapinska A et al (2010) Increased production of a proliferation-inducing ligand (APRIL) by peripheral blood mononuclear cells is associated with antitopoisomerase I antibody and more severe disease in systemic sclerosis. J Rheumatol 37:2286–2289. https://doi.org/10.3899/jrheum.100454CrossRefPubMed

50.

Melissaropoulos K, Liossis S-N (2018) Decreased CD22 expression and intracellular signaling aberrations in B cells of patients with systemic sclerosis. Rheumatol Int 38:1225–1234. https://doi.org/10.1007/s00296-018-4076-3CrossRefPubMed

51.

Tsuchiya N, Kuroki K, Fujimoto M, Murakami Y, Tedder TF, Tokunaga K, Takehara K, Sato S (2004) Association of a functionalCD19 polymorphism with susceptibility to systemic sclerosis. Arthritis Rheum 50:4002–4007. https://doi.org/10.1002/art.20674CrossRefPubMed

52.

Hitomi Y, Tsuchiya N, Hasegawa M et al (2007) Association of CD22 gene polymorphism with susceptibility to limited cutaneous systemic sclerosis. Tissue Antigens 69:242–249. https://doi.org/10.1111/j.1399-0039.2007.00801.xCrossRefPubMed

53.

Yagi-Numata N, Matsushita T, Takehara K, Hamaguchi Y (2019) Increased expression levels of FcγRIIB on naïve and double- negative memory B cells in patients with systemic sclerosis. Clin Exp Rheumatol 37 Suppl 119:23–31

54.

Lafyatis R, O’Hara C, Feghali-Bostwick CA, Matteson E (2007) B cell infiltration in systemic sclerosis–associated interstitial lung disease. Arthritis Rheum 56:3167–3168. https://doi.org/10.1002/art.22847CrossRefPubMed

55.

De Santis M, Bosello SL, Peluso G et al (2012) Bronchoalveolar lavage fluid and progression of scleroderma interstitial lung disease: scleroderma interstitial lung disease. Clin Respir J 6:9–17. https://doi.org/10.1111/j.1752-699X.2010.00228.xCrossRefPubMed

56.

Fleischmajer R, Perlish JS, Reeves JRT (1977) Cellular infiltrates in scleroderma skin. Arthritis Rheum 20:975–984. https://doi.org/10.1002/art.1780200410CrossRefPubMed

57.

Roumm AD, Whiteside TL, Medsger TA, Rodnan GP (1984) Lymphocytes in the skin of patients with progressive systemic sclerosis. Arthritis Rheum 27:645–653. https://doi.org/10.1002/art.1780270607CrossRefPubMed

58.

Whitfield ML, Finlay DR, Murray JI, Troyanskaya OG, Chi JT, Pergamenschikov A, McCalmont TH, Brown PO, Botstein D, Connolly MK (2003) Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci 100:12319–12324. https://doi.org/10.1073/pnas.1635114100CrossRefPubMed

59.

Milano A, Pendergrass SA, Sargent JL, George LK, McCalmont TH, Connolly MK, Whitfield ML (2008) Molecular subsets in the gene expression signatures of scleroderma skin. PLoS ONE 3:e2696. https://doi.org/10.1371/journal.pone.0002696CrossRefPubMedPubMedCentral

60.

Skaug B, Khanna D, Swindell WR, Hinchcliff ME, Frech TM, Steen VD, Hant FN, Gordon JK, Shah AA, Zhu L, Zheng WJ, Browning JL, Barron AMS, Wu M, Visvanathan S, Baum P, Franks JM, Whitfield ML, Shanmugam VK, Domsic RT, Castelino FV, Bernstein EJ, Wareing N, Lyons MA, Ying J, Charles J, Mayes MD, Assassi S (2020) Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Ann Rheum Dis 79:379–386. https://doi.org/10.1136/annrheumdis-2019-215894CrossRefPubMed

61.

Bosello S, Angelucci C, Lama G, Alivernini S, Proietti G, Tolusso B, Sica G, Gremese E, Ferraccioli G (2018) Characterization of inflammatory cell infiltrate of scleroderma skin: B cells and skin score progression. Arthritis Res Ther 20:75. https://doi.org/10.1186/s13075-018-1569-0CrossRefPubMedPubMedCentral

62.

Usategui A, del Rey MJ, Pablos JL (2011) Fibroblast abnormalities in the pathogenesis of systemic sclerosis. Expert Rev Clin Immunol 7:491–498. https://doi.org/10.1586/eci.11.39CrossRefPubMed

63.

Worrell JC, O’Reilly S (2020) Bi-directional communication: conversations between fibroblasts and immune cells in systemic sclerosis. J Autoimmun 113:102526. https://doi.org/10.1016/j.jaut.2020.102526CrossRefPubMed

64.

Daoussis D, Liossis S-NC (2013) B cells tell scleroderma fibroblasts to produce collagen. Arthritis Res Ther 15:125. https://doi.org/10.1186/ar4392CrossRefPubMedPubMedCentral

65.

Terrier B, Tamby MC, Camoin L, Guilpain P, Bérezné A, Tamas N, Broussard C, Hotellier F, Humbert M, Simonneau G, Guillevin L, Mouthon L (2010) Antifibroblast antibodies from systemic sclerosis patients bind to α-enolase and are associated with interstitial lung disease. Ann Rheum Dis 69:428–433. https://doi.org/10.1136/ard.2008.104299CrossRefPubMed

66.

Hénault J, Tremblay M, Clément I, Raymond Y, Senécal JL (2004) Direct binding of anti-DNA topoisomerase I autoantibodies to the cell surface of fibroblasts in patients with systemic sclerosis: antifibroblast autoantibodies in SSc. Arthritis Rheum 50:3265–3274. https://doi.org/10.1002/art.20515CrossRefPubMed

67.

Fineschi S, Goffin L, Rezzonico R, Cozzi F, Dayer JM, Meroni PL, Chizzolini C (2008) Antifibroblast antibodies in systemic sclerosis induce fibroblasts to produce profibrotic chemokines, with partial exploitation of toll-like receptor 4. Arthritis Rheum 58:3913–3923. https://doi.org/10.1002/art.24049CrossRefPubMed

68.

Baroni SS, Luchetti M, Fraticelli P et al (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 10

69.

Loizos N, LaRiccia L, Weiner J et al (2009) Lack of detection of agonist activity by antibodies to platelet-derived growth factor receptor α in a subset of normal and systemic sclerosis patient sera. Arthritis Rheum 60:1145–1151. https://doi.org/10.1002/art.24365CrossRefPubMed

70.

Classen J-F, Henrohn D, Rorsman F, Lennartsson J, Lauwerys BR, Wikström G, Rorsman C, Lenglez S, Franck-Larsson K, Tomasi JP, Kämpe O, Vanthuyne M, Houssiau FA, Demoulin JB (2009) Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis. Arthritis Rheum 60:1137–1144. https://doi.org/10.1002/art.24381CrossRefPubMed

71.

Sato S, Hayakawa I, Hasegawa M, Takehara K, Fujimoto M (2003) Function blocking autoantibodies against matrix metalloproteinase-1 in patients with systemic sclerosis. J Invest Dermatol 120:542–547. https://doi.org/10.1046/j.1523-1747.2003.12097.xCrossRefPubMed

72.

Zhou X, Tan FK, Milewicz DM, Guo X, Bona CA, Arnett FC (2005) Autoantibodies to fibrillin-1 activate normal human fibroblasts in culture through the TGF-pathway to recapitulate the “scleroderma phenotype”. J Immunol 175:4555–4560. https://doi.org/10.4049/jimmunol.175.7.4555CrossRefPubMed

73.

Sato S, Hasegawa M, Takehara K (2001) Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis. J Dermatol Sci 27:140–146. https://doi.org/10.1016/S0923-1811(01)00128-1CrossRefPubMed

74.

François A, Chatelus E, Wachsmann D, Sibilia J, Bahram S, Alsaleh G, Gottenberg JE (2013) B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis. Arthritis Res Ther 15:R168. https://doi.org/10.1186/ar4352CrossRefPubMedPubMedCentral

75.

Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655–2666. https://doi.org/10.1056/NEJMoa055120CrossRefPubMed

76.

Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM, Sclerodema Lung Study II Investigators (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4:708–719. https://doi.org/10.1016/S2213-2600(16)30152-7CrossRefPubMedPubMedCentral

77.

Van Laar JM, Sullivan K (2013) Stem cell transplantation in systemic sclerosis. Curr Opin Rheumatol 25:719–725. https://doi.org/10.1097/01.bor.0000434669.32150.acCrossRefPubMed

78.

Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, Mayes MD, Nash RA, Crofford LJ, Eggleston B, Castina S, Griffith LM, Goldstein JS, Wallace D, Craciunescu O, Khanna D, Folz RJ, Goldin J, St. Clair EW, Seibold JR, Phillips K, Mineishi S, Simms RW, Ballen K, Wener MH, Georges GE, Heimfeld S, Hosing C, Forman S, Kafaja S, Silver RM, Griffing L, Storek J, LeClercq S, Brasington R, Csuka ME, Bredeson C, Keever-Taylor C, Domsic RT, Kahaleh MB, Medsger T, Furst DE (2018) Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med 378:35–47CrossRef

79.

Gernert M, Tony H-P, Schwaneck EC, Gadeholt O, Schmalzing M (2019) Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern. Arthritis Res Ther 21:106. https://doi.org/10.1186/s13075-019-1889-8CrossRefPubMedPubMedCentral

80.

Misra DP, Ahmed S, Agarwal V (2020) Is biological therapy in systemic sclerosis the answer? Rheumatol Int 40:679–694. https://doi.org/10.1007/s00296-020-04515-6CrossRefPubMed

81.

Bellan M, Patrucco F, Barone-Adesi F, Gavelli F, Castello LM, Nerviani A, Andreoli L, Cavagna L, Pirisi M, Sainaghi PP (2020) Targeting CD20 in the treatment of interstitial lung diseases related to connective tissue diseases: a systematic review. Autoimmun Rev 19:102453. https://doi.org/10.1016/j.autrev.2019.102453CrossRefPubMed

82.

Daoussis D, Liossis S-NC, Tsamandas AC et al (2010) Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology 49:271–280. https://doi.org/10.1093/rheumatology/kep093CrossRefPubMed

83.

Sircar G, Goswami RP, Sircar D, Ghosh A, Ghosh P (2018) Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial. Rheumatology 57:2106–2113. https://doi.org/10.1093/rheumatology/key213CrossRefPubMed

84.

Boonstra M, Meijs J, Dorjée AL, Marsan NA, Schouffoer A, Ninaber MK, Quint KD, Bonte-Mineur F, Huizinga TWJ, Scherer HU, de Vries-Bouwstra JK (2017) Rituximab in early systemic sclerosis. RMD Open 3:e000384. https://doi.org/10.1136/rmdopen-2016-000384CrossRefPubMedPubMedCentral

85.

Lafyatis R, Kissin E, York M, Farina G, Viger K, Fritzler MJ, Merkel PA, Simms RW (2009) B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum 60:578–583. https://doi.org/10.1002/art.24249CrossRefPubMedPubMedCentral

86.

Smith V, Van Praet JT, Vandooren B et al (2010) Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis 69:193–197. https://doi.org/10.1136/ard.2008.095463CrossRefPubMed

87.

Bosello S, De Santis M, Lama G et al (2010) 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 12:R54. https://doi.org/10.1186/ar2965CrossRefPubMedPubMedCentral

88.

Thiebaut M, Launay D, Rivière S, Mahévas T, Bellakhal S, Hachulla E, Fain O, Mekinian A (2018) Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review. Autoimmun Rev 17:582–587. https://doi.org/10.1016/j.autrev.2017.12.010CrossRefPubMed

89.

Melsens K, Vandecasteele E, Deschepper E, Badot V, Blockmans D, Brusselle G, de Langhe E, de Pauw M, Debusschere C, Decuman S, Deroo L, Houssiau F, Lenaerts J, Piette Y, Thevissen K, Vanthuyne M, Westhovens R, Wijnant S, de Keyser F, Smith V (2018) Two years follow-up of an open-label pilot study of treatment with rituximab in patients with early diffuse cutaneous systemic sclerosis. Acta Clin Belg 73:119–125. https://doi.org/10.1080/17843286.2017.1372244CrossRefPubMed

90.

Narváez J, LLuch J, Molina-Molina M et al (2020) Rituximab as a rescue treatment added on mycophenolate mofetil background therapy in progressive systemic sclerosis associated interstitial lung disease unresponsive to conventional immunosuppression. Semin Arthritis Rheum 50:977–987. https://doi.org/10.1016/j.semarthrit.2020.08.004CrossRefPubMed

91.

Daoussis D, Liossis S-NC, Tsamandas AC et al (2012) Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. Clin Exp Rheumatol 30:S17–S22PubMed

92.

Daoussis D, Melissaropoulos K, Sakellaropoulos G, Antonopoulos I, Markatseli TE, Simopoulou T, Georgiou P, Andonopoulos AP, Drosos AA, Sakkas L, Liossis SN (2017) A multicenter, open-label, comparative study of B-cell depletion therapy with rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum 46:625–631. https://doi.org/10.1016/j.semarthrit.2016.10.003CrossRefPubMed

93.

Bosello SL, De Luca G, Rucco M et al (2015) Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis. Semin Arthritis Rheum 44:428–436. https://doi.org/10.1016/j.semarthrit.2014.09.002CrossRefPubMed

94.

Jordan S, Distler JHW, Maurer B, Huscher D, van Laar J, Allanore Y, Distler O, EUSTAR Rituximab study group (2015) Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 74:1188–1194. https://doi.org/10.1136/annrheumdis-2013-204522CrossRefPubMed

95.

Elhai M, Boubaya M, Distler O, Smith V, Matucci-Cerinic M, Alegre Sancho JJ, Truchetet ME, Braun-Moscovici Y, Iannone F, Novikov PI, Lescoat A, Siegert E, Castellví I, Airó P, Vettori S, de Langhe E, Hachulla E, Erler A, Ananieva L, Krusche M, López-Longo FJ, Distler JHW, Hunzelmann N, Hoffmann-Vold AM, Riccieri V, Hsu VM, Pozzi MR, Ancuta C, Rosato E, Mihai C, Kuwana M, Saketkoo LA, Chizzolini C, Hesselstrand R, Ullman S, Yavuz S, Rednic S, Caimmi C, Bloch-Queyrat C, Allanore Y, for EUSTAR network (2019) Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study. Ann Rheum Dis 78:979–987. https://doi.org/10.1136/annrheumdis-2018-214816CrossRefPubMed

96.

Goswami RP, Ray A, Chatterjee M et al (2020) Rituximab in the treatment of systemic sclerosis–related interstitial lung disease: a systematic review and meta-analysis. Rheumatology. https://doi.org/10.1093/rheumatology/keaa550

97.

Tang R, Yu J, Shi Y, Zou P, Zeng Z, Tang B, Wang Y, Ling G, Luo M, Xiao R (2020) Safety and efficacy of rituximab in systemic sclerosis: a systematic review and meta-analysis. Int Immunopharmacol 83:106389. https://doi.org/10.1016/j.intimp.2020.106389CrossRefPubMed

98.

Hughes M, Denton CP, Khanna D (2020) Rituximab for the treatment of systemic sclerosis-interstitial lung disease. Rheumatology. https://doi.org/10.1093/rheumatology/keaa675

99.

Gordon JK, Martyanov V, Franks JM, Bernstein EJ, Szymonifka J, Magro C, Wildman HF, Wood TA, Whitfield ML, Spiera RF (2018) Belimumab for the treatment of early diffuse systemic sclerosis: results of a randomized, double-blind, placebo-controlled, pilot trial. Arthritis Rheum 70:308–316. https://doi.org/10.1002/art.40358CrossRef

100.

Schiopu E, Chatterjee S, Hsu V, Flor A, Cimbora D, Patra K, Yao W, Li J, Streicher K, McKeever K, White B, Katz E, Drappa J, Sweeny S, Herbst R (2016) Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study. Arthritis Res Ther 18:1–14. https://doi.org/10.1186/S13075-016-1021-2CrossRef

101.

Streicher K, Sridhar S, Kuziora M, Morehouse CA, Higgs BW, Sebastian Y, Groves CJ, Pilataxi F, Brohawn PZ, Herbst R, Ranade K (2018) Baseline plasma cell gene signature predicts improvement in systemic sclerosis skin scores following treatment with inebilizumab (MEDI-551) and correlates with disease activity in systemic lupus erythematosus and chronic obstructive pulmonary disease. Arthritis Rheum 70:2087–2095. https://doi.org/10.1002/art.40656CrossRef

102.

Daoussis D, Liossis S-N (2019) Treatment of systemic sclerosis associated fibrotic manifestations: current options and future directions. Mediterr J Rheumatol 30:33–37. https://doi.org/10.31138/mjr.30.1.33CrossRefPubMedPubMedCentral

103.

Dimitroulas T, Daoussis D, Garyfallos A, Sfikakis P, Kitas G (2015) Molecular and cellular pathways as treatment targets for biologic therapies in systemic sclerosis. Curr Med Chem 22:1943–1955. https://doi.org/10.2174/0929867322666150209161224CrossRefPubMed

104.

Melissaropoulos K, Kraniotis P, Bogdanos D, Dimitroulas T, Sakkas L, Daoussis D (2019) Targeting very early systemic sclerosis: a case-based review. Rheumatol Int 39:1961–1970. https://doi.org/10.1007/s00296-019-04357-xCrossRefPubMed

105.

Antonopoulos I, Daoussis D, Lalioti M-E, Markatseli TE, Drosos AA, Taraviras S, Andonopoulos AP, Liossis SNC (2019) B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis. Rheumatol Int 39:1889–1898. https://doi.org/10.1007/s00296-019-04350-4CrossRefPubMed

106.

Daoussis D, Tsamandas A, Antonopoulos I, Filippopoulou A, Papachristou DJ, Papachristou NI, Andonopoulos AP, Liossis SN (2016) B cell depletion therapy upregulates Dkk-1 skin expression in patients with systemic sclerosis: association with enhanced resolution of skin fibrosis. Arthritis Res Ther 18:118. https://doi.org/10.1186/s13075-016-1017-yCrossRefPubMedPubMedCentral

Titel: B cells in systemic sclerosis: from pathophysiology to treatment
verfasst von: Konstantinos Melissaropoulos
Dimitrios Daoussis
Publikationsdatum: 21.03.2021
Verlag: Springer International Publishing
Erschienen in: Clinical Rheumatology / Ausgabe 7/2021
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-021-05665-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2021

A critical review of the available evidence on the diagnosis and clinical features of CPPD: do we really need imaging?

Visceral adipose tissue in granulomatosis with polyangiitis: association with disease activity parameters

Dorsolateral medullary infarction during skin infection by Stenotrophomonas maltophilia in a patient with triple antiphospholipid antibody positivity: a case-based review

Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1

Drug retention of sarilumab, baricitinib, and tofacitinib in patients with rheumatoid arthritis: the ANSWER cohort study