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Modulatory Effect of the Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen on Circulating Immune Cells in Systemic Lupus Erythematosus

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

A Euro-Lupus regimen of low-dose intravenous cyclophosphamide (CFA) is commonly used to treat severe organ manifestations of systemic lupus erythematosus (SLE), particularly lupus nephritis (LN). There are no data on the distributions and dynamics of immune cell populations in patients with various treatment outcomes. The circulating immune cells of 11 female SLE patients were assessed before and after Euro-Lupus regimen (cumulative dose of 3000 mg CFA) by flow cytometry together with those of 16 healthy women. A subanalysis was performed in LN patients who achieved complete remission (CR; n = 3), partial remission (PR; n = 4), and no response (NR; n = 2). In SLE, the Euro-Lupus regimen decreased the percentage and absolute count of B cells; increased the percentage of CD8+ T cells, T regulatory cells, neutrophils, and monocyte subsets; and activated T and NK cells compared to healthy controls (P < 0.050). Patients with LN achieving CR had significantly lower proportions of CD27+ B memory cells compared to poor responders (PR/NR, P = 0.035). The post-treatment percentages and absolute numbers of B cells, T cells, NK cells, monocytes, and neutrophils showed high inter-individual variability with no association with treatment outcome. Our pilot study revealed the dynamics of changes in immune cell populations in SLE patients during a Euro-Lupus regimen, mainly the lowering of B cells. In LN patients who achieved CR, a lower proportion of CD27+ B memory cells was evident compared to poor responders (PR/NR). Further studies on usefulness of monitoring immune cells for treatment response prediction on larger cohorts are needed.

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Acknowledgements

We would like to thank Mr. Jakub Savara, for his kind help with figures.

Funding

This work was supported by the Internal Grant Agency of Palacký University (IGA_LF_2019_006, and IGA_LF_2019_014), and, in part, by the Ministry of Health of Czech Republic (MH CZ—DRO (FNOL, 00098892).

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Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc, University Hospital Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic

    Gabriela Gabcova, Zuzana Mikulkova, Anna Petrackova, Frantisek Mrazek & Eva Kriegova

  2. Department of Internal Medicine III—Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacký University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic

    Pavel Horak, Martina Skacelova & Andrea Smrzova

  3. Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava, Czech Republic

    Sarka Zehnalova

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  1. Gabriela Gabcova
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Contributions

GG, ZM, AP: laboratory measurement, GG, SZ: statistical analysis, GG, EK: writing of the manuscript and interpretation of data, PH, MS, AS: collection of clinical data, PH, FM, MZ: critical revision of the manuscript, EK, PH: study design.

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Correspondence to Eva Kriegova.

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Gabcova, G., Horak, P., Mikulkova, Z. et al. Modulatory Effect of the Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen on Circulating Immune Cells in Systemic Lupus Erythematosus. Arch. Immunol. Ther. Exp. 67, 415–425 (2019). https://doi.org/10.1007/s00005-019-00563-4

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