MO220: Comparison of the Effects of Hydroxychloroquine and Glucocorticosteroids on Immunological Parametrs in Patients with IGA Nephropathy

Abstract

Abstract BACKGROUND AND AIMS Current treatment strategies of IgA nephropathy (IgAN) primarily involve blood pressure control, renin–angiotensin–aldosterone system inhibitors (RAASIs), and glucocorticosteroids (GCs), which are recommended when the supporting therapies fail to reduce proteinuria (PU) levels below 1 g/day. Hydroxychloroquine (HCQ) is considered to have an immunomodulatory rather than an immunosuppressant effect. The immune pathways targeted by HCQ are not fully investigated during treatment of IgAN. The aim of this study was to compare effects of HCQ and GCs on immunological parameters in patients with IgAN. METHOD 32 IgAN patients aged 32.0 (26.7 ÷ 36.0) y.o., male/female ratio as 24/8 with PU > 1 g/day and estimated glomerular filtration rate (eGFR) 78 (61; 103) mL/min were divided into three treatment groups: RAASIs (n = 12); HCQ (n = 10); GCs Pozzi protocol (n = 10). The changes in clinical and immunological parameters were analyzed 6 months after treatment. Phenotypic and functional markers of peripheral blood lymphoid cells were identified by flow cytometry method (Cytoflex, «Beckman Coulter», USA). The concentrations of total immunoglobulins (Ig) class M, G, A and E were determined by ELISA method («VectorBest», Russia). Statistical analysis was done using Statistica 8.0. RESULTS After 6 months of treatment HCQ has shown effectiveness in decreasing of PU (P < .001), haematuria level (P <.01) as well as the same effect was noted in the other treatment groups after 6 months course. The renal function was stable in all investigated groups during follow up. There were no any adverse effects of the treatment. The decrease of potential cytotoxic γδTCR+Т-cells (P <.01) and CD3 + 56 + TNK-cells (P < .01) numbers in peripheral blood (Fig. 1) as well as the reduction of IgM (P < 0.05) and IgG (P < .05) serum levels (Table 1) were established in patients receiving HCQ. While GCs treatment resulted in CD3 + T-cells (P < .05) suppression (Fig. 1) mainly due to CD3 + CD4 + T-helpers down-regulation (P < .05) but stimulation of cytotoxic CD3 + CD8 + T-cells (P < .05) (data not shown) and increasing of IgE level (P < .05) (Table 1). It was not revealed any influence of RAASIs treatment either on the number of lymphoid cells populations (Fig. 1) or Ig levels. CONCLUSION This study demonstrates different ways of pathogenic treatment in IgAN. HCQ has exhibited an immunomodulatory action on the effector mechanisms of cellular cytotoxicity via minor lymphoid T-cells populations reduction as well as on productive phase of humoral immunity via IgM and IgG levels decreasing. While GCs have suppressed CD3 + T-cell and supported IgE-mediated autoinflammation.