Artikel
B cell-bound complement activation products in the diagnosis and monitoring of systemic lupus erythematosus (SLE)
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Veröffentlicht: | 1. September 2015 |
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Gliederung
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Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of a broad array of pathogenic autoantibodies and diverse clinical phenotype. The clinical heterogeneity and miscellaneous pathogenic mechanisms involved renders the diagnosis and follow up of the patients difficult. Biomarkers applicable in diagnosis, treatment stratification and a long-term prognostication are needed. Complement activation is implicated in pathogenesis of SLE. C3 and C4 assessment is used in SLE diagnostics and monitoring, as decrease in their serum levels reflects complement activation and correlates with disease activity with considerable limitations due to the following: a) individual C3 and C4 serum levels vary considerably and are impacted by genetic deficiencies and the inflammatory acute phase response; b) assays measure total intact C3 and C4 rather than products of activation. Direct measurement of complement activation products (CAP; C3a, C5a, C3d, C4d) is thus more accurate. The instability of CAPs requires careful pre-analytical handling of blood samples and rapid processing; these conditions are not always feasible in clinical routine. CAP bound to cellular surfaces (CB-CAP) might offer a more flexible alternative. A covalent bond stabilizes CB-CAPs and enables their quantification via routine flow cytometry analysis up to 24 hours after blood drawing.
Methods: We have analysed C4d bound to lymphocytes in 50 adult patients with SLE, 24 patients with other autoimmune diseases and 47 healthy controls.
Results: We have found a good correlation of C4d bound to B-lymphocytes (B-C4d) with the standard parameters (C4: r = -0.309, p = 0.013, C3: r= - 0.356, p = 0.004, dsDNA: r = 0.574, p < 0.001 and plasma C3d: r = 0.319, p = 0.009).
Conclusion: Our data show that surface B-C4d level correlates with established disease activity markers, and given its easier handling, is of possible utility in routine diagnostic and monitoring of patients with SLE. A multicentre study for evaluation of this method in a cohort of paediatric patients is planned.