#5639 TARGETING BAFF AND APRIL IN IGA-NEPHROPATHY

Abstract

Abstract Background and Aims B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are critical factors in the differentiation and longevity maintenance of the B-cells pool thereby mediating humoral immunity. BAFF and APRIL are involved in initiating B-cells to become self-reactive and elevated levels of these cytokines are detected in the sera of patients with systemic autoimmune diseases. The aim of the study was to estimate role of APRIL and BAFF in IgA-nephropathy (IgAN) patients and to determine the appropriate IgAN treatment based on the assessment of BAFF and APRIL dynamics in IgAN patients’ sera after 6 months of different treatments. Method The 52 IgAN patients aged 32,0 (27,0; 36,0) y.o., male/female ratio as 34/18 despite using of renin-angiotensin-aldosterone system inhibitors (RAASIs) for 6 months with PU 1,8 (1,0; 1,9) g/day and estimated glomerular filtration rate (eGFR) 78 (61; 103) ml/min were divided into 3 treatment groups: 1 group (n = 20) – 200 mg hydroxychloroquine (HCQ) twice a day, 2 group (n = 20) – received glucocorticoids (GC) regimen Pozzi protocol, 3 group (n = 12) – received (RAASIs) in maximal tolerated dose. The control group included age- and sex-matched healthy donors (n = 10). The number of B-cells in peripheral blood was identified by flow cytometry method. The concentrations of total IgM, IgG, IgA, IgE, APRIL and BAFF were determined by ELISA method using commercial kits. Statistical analysis was done using Statistica 10.0. Results Despite the absence of statistically significant differences in the number of B-lymphocytes the increased levels of total IgM, IgA and IgE (p = 0,001) as well as APRIL (5336 (3574; 5965) pg/ml vs 4543 (4518 ÷ 4755) pg/ml (p = 0,05) and BAFF 378 (191; 541) vs 336 (257; 424) pg/ml (p = 0,07) were established in sera of IgAN patients as compared to control group, respectively. The initial APRIL level was correlated with the degree of tubular atrophy with interstitial fibrosis (R = 0,40, p = 0,05) and serum IgG level (R = 0,35, p = 0,05) in IgAN patients. After 6 months of treatment proteinuria was significantly reduced in HCQ (p = 0,03) and GC (p = 0,02) groups while kidney function was stable in all patients. The dynamic of immunological parameters is presented in the Table 1. It was established that HCQ treatment in IgAN patients decreased the production of IgM (p = 0,01) and IgG (p = 0,02) as well as serum concentration of the APRIL factor (p = 0,05) what correlated with the tendency to eGFR increase (R = –0,46, p = 0,06) as well as with clinical effect of therapy improvement of (R = –0,45, p = 0,04). There were no statistical changes in the level of the BAFF factor in patients with HCQ. After GC treatment a decrease in the synthesis of serum IgA (p = 0,01) as well as trend to decline of B-cells number (p = 0,07) were determined, while in patients treated with RAASIs a significant increase in IgE production (p = 0,05) and tendency in elevation in BAFF levels (p = 0,06) were observed. Conclusion Immunological changes may be the determining factors in the choice of treatment in IgAN patients.