FRI0326 Immune cellular profile associated with different treatment outcome in patients with systemic lupus erythematosus on cyclophosphamide

Background Cyclophosphamide (CFA) is an effective immunosuppressive drug used for treatment of severe manifestations of systemic lupus erythematosus (SLE). The knowledge about modulatory effect of CFA on circulating immune cells and its changes associated with treatment response is limited. Objectives To determine the effect of a cumulative dose of CFA on circulating immune cells in SLE patients and to assess its association with treatment outcome. Methods Using 6-colour flow cytometry (BD FACSCanto II) we analysed T and B lymphocytes, NK cells, neutrophils, and monocytes in peripheral blood from 11 SLE female patients. SLE patients were investigated before and after cumulative 1000 mg and 3000 mg of CFA dose. Patients subgroups were assessed according to the treatment response (n=5, good responders; n=6, poor responders); SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) was used to assess the disease activity. Healthy age-matched females (n=12) were included in the study. Statistics was done by GraphPad Prism and R statistical software package. Results Cumulative dose of 1000 mg of CFA resulted in decreased percentage of B lymphocytes (p=0.0004) and CD4 +T lymphocytes (p=0.02) and increased the percentage of total and CD8 +T lymphocytes (p=0.03; p=0.0003 respectively). After 3000 mg CFA, the percentage of B lymphocytes (p=0.002), naive B lymphocytes (p=0.005), memory B lymphocytes (p=0.02) and CD4+/CD8 +ratio (p=0.01) decreased while the percentage of CD8 +T lymphocytes (p=0.0003), Tregs (p=0.01) and CD69 +NK cells (p=0.02) increased. CFA treatment in our patients resulted in reduction of B lymphocyte percentage reaching the values of healthy controls. In good responders, decreased percentage of B lymphocytes (p=0.04), CD4 +T lymphocytes (p=0.04), CD4+/CD8 +ratio (p=0.007) and increased percentage of CD8 +T lymphocytes (p=0.004), CD69 +NK cells (p=0.04) and nonclassical monocytes (p=0.04). In poorly responding patients percentage of CD8 +T lymphocytes (p=0.01), activation marker HLA-DR on both CD4 +and CD8+T lymphocytes (p=0.01; p=0.02 respectively), Tregs (p=0.02), memory B lymphocytes (p=0.03) were increased and percentage of total B lymphocytes was decreased (p=0.02). The analysis using advanced data mining methods for identification of treatment outcome related profiles are ongoing Conclusions Administration of CFA modulates several cell populations in SLE patients, whereas changes in B and T lymphocytes were associated with different treatment outcome. Whether the immune profile may predict the treatment response deserves further investigation. Acknowledgements MZ CR VES15–28659A, IGA_LF_2018_016 Disclosure of Interest None declared