Abstract
In view of its heterogeneous presentation and unpredictable course, clinical management of systemic lupus erythematosus (SLE) is difficult. There is a need for biomarkers and diagnostic aids to monitor SLE disease activity and severity prior to, during and after treatment. We undertook this study to search for unique phenotypic patterns in each peripheral blood (PB) B cell subset, capable of distinguishing SLE patients with inactive disease versus SLE patients with active disease versus controls by using an automated population separator (APS) visualization strategy. PB was collected from 41 SLE patients and 28 age- and gender-matched controls. We analyzed the cell surface markers (in a tube CD20/CD27/CD19/CD45/CD38/CD81/BAFFR combination) expression on PB B cell subsets using principal component analysis, implemented in the APS software tool. Overall, our analysis indicates that active SLE can be distinguished from inactive SLE on the basis of a single tube analysis, focused on the decreased expression of CD38, CD81 and BAFFR in transitional B cells. The cluster analysis of immunophenotypic profiles of B cell subsets highlighted disease-specific abnormalities on transitional B cells that emerge as promising surrogate markers for disease activity. Further validation is needed with larger samples and prospective follow-up of patients.
References
Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 2003;56:481–90.
Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358:929–39.
Arbuckle MR, Mc Clain MT, Rubertone MV, Hal Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349:1526–e1533.
Wang LD, Clark MR. B-cell antigen-receptor signalling in lymphocyte development. Immunology. 2003;110:411–20.
Batten M, Groom J, Cachero TG, et al. BAFF mediates survival of peripheral immature B lymphocytes. J Exp Med. 2000;192:1453–66.
Vences-Catalán F, Rajapaksa R, Levy S, Santos-Argumedo L. The CD19/CD81 complex physically interacts with CD38 but is not required to induce proliferation in mouse B lymphocytes. Immunology. 2012;137:48–55.
Chen J, Chen Y, Reifsnyder PC, et al. Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion. J Immunol. 2006;176:4590–9.
Pers JO, Daridon C, Devauchelle V, et al. BAFF overexpression is associated with autoantibody production in autoimmune diseases. Ann N Y Acad Sci. 2005;1050:34–9.
Petri M, Stohl W, Chatham W, et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008;58:2453–9.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum. 1992;35:630–40.
Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288–91.
Sanchez ML, Almeida J, Vidriales B, et al. Incidence of phenotypic aberrations in a series of 467 patients with B chronic lymphoproliferative disorders: basis for the design of specific four-color stainings to be used for minimal residual disease investigation. Leukemia. 2002;16:1460–9.
Costa ES, Pedreira CE, Barrena S, et al. Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical cytometry. Leukemia. 2010;24:1927–33.
Ulgiati D, Pham C, Holers VM. Functional analysis of the human complement receptor 2 (CR2/CD21) promoter: characterization of basal transcriptional mechanisms. J Immunol. 2002;168:6279–85.
van Dongen JJ, Lhermitte L, Böttcher S, et al. EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708). EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012;26:1908–75.
Asokan R, Banda NK, Szakonyi G, Chen XS, Holers VM. Human complement receptor 2 (CR2/CD21) as a receptor for DNA: implications for its roles in the immune response and the pathogenesis of systemic lupus erythematosus (SLE). Mol Immunol. 2013;53:99–110.
Viegas MS, Silva T, Monteiro MM, do Carmo A, Martins TC. Knocking out of CD38 accelerates development of a lupus-like disease in lpr mice. Rheumatology (Oxford). 2011;50:1569–77.
Sellam J, Miceli-Richard C, Gottenberg JE, et al. Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjögren’s syndrome and systemic lupus erythematosus. Ann Rheum Dis. 2007;66:790–7.
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This work was supported by the Faculty of Medicine, University of Coimbra Grant.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Ana Henriques and Isabel Silva have contributed equally to this study.
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Henriques, A., Silva, I., Inês, L. et al. CD38, CD81 and BAFFR combined expression by transitional B cells distinguishes active from inactive systemic lupus erythematosus. Clin Exp Med 16, 227–232 (2016). https://doi.org/10.1007/s10238-015-0348-3
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DOI: https://doi.org/10.1007/s10238-015-0348-3