THU0238 P-glycoprotein monoclonal antibody improves lupus-like syndrome in MRL/LPR mice
Authors: M Wang, P Zeng, G Zhou, J Lv, Q Wang
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Preventing steroid resistance and maintaining disease control are significant challenges to overcome in treating SLE patients<sup>[1]</sup>. P-glycoprotein (P-gp) of membrane transporters, a product of the multiple drug resistance (MDR)-1 gene, is known to play a pivotal role in the acquisition of drug resistance to chemotherapy in autoimmune diseases<sup>[2]</sup>.Inhibition of P-gp could overcome such drug resistance<sup>[3,4]</sup>. So we observed the effect of P-gp monoclonal antibody on MRL/lpr lupus mice. <h3>Objectives</h3> To investigate the efficacy of P-glycoprotein monoclonal antibody in the treatment of the MRL/lpr mice. <h3>Methods</h3> Twenty four 14- week- old MRL/lpr female mice were divided into 3groups:group 1 (G1)were treated with P-glycoprotein monoclonal through caudal vein, group 2 (G2)were treated with P-glycoprotein monoclonal three times and group 0 (G0)were treated with 0.5ml normal saline as controls. Twenty-four hours proteinuria and body weight were assessed every two weeks.Enzyme linked immunosorbent assay (ELISA)was used to measure the levels of serum anti-dsDNA antibodies. The histopathology changes of the kidneys were observed. <h3>Results</h3> From the 22th week,the body weight of groups Gl and G2 increased significantly than that of the group G0 (<i>p</i>&lt;0.05). At the 22th weeks,the 24 hours proteinuria in group Gl (1.9±1.1)mg and G2 (1.4±0.9)mg was decreased than that in group G0 (3.1+1.9)mg (<i>p</i>&lt;0.05), and at the 26th weeks,that of groups G1 (2.4±1.4)mg and G2 (1.8±1.1)mg was also significantly decreased than in group G0 (5.3±2.2)mg (<i>p</i>&lt;0.01). At week 26,serum creatinine decreased significantly in both groups G1 (7.0±2.9)umol/L and G2 (6.1±2.5)umol/L than in group G0 (12.7±1.3)umol/L (<i>p</i>&lt;0.05). One week after treatment, the levels of anti-dsDNA antibodies in group Gl (43±19)x10<sup>2</sup> U/ml and G2 (45±32)x10<sup>2</sup> U/ml were both significantly decreased than those of the group G0 (87±39)x10<sup>2</sup> U/ml (<i>p</i>&lt;0.05),and at the 26th weeks the difference between group G2 (35±11)xl0<sup>2</sup> U/ml and G0 (59±35)x10<sup>2</sup> U/ml was statistically significant. The nephron crescent formation in group G1 (0.11±0.05)and G2 (0.09±0.01)was significandy lower that of the group G0 (0.23±0.07) (<i>p</i>&lt;0.05), and that of group G2 was significantly less that of group Gl (<i>p</i>&lt;0.05). <h3>Conclusions</h3> P-glycoprotein monoclonal antibody is very effective in treating MRL/lpr mice.It is safe and free of rejection reactions. <h3>References</h3> Barnes PJ.Mechanisms and resistance in glucocorticoid control of inflammation. J Steroid Biochem Mol Biol. 2010,120(2–3):76–85. García-Carrasco M, Mendoza-Pinto C, Macias Díaz S, et al. P-glycoprotein in autoimmune rheumatic diseases.See comment in PubMed Commons belowAutoimmun Rev.2015,14(7):594–600. Advani R, Visani G, Milligan D, Saba H, Tallman M, Rowe JM,et al. Treatment of poor prognosis AML patients using PSC833 (valspodar) plus mitoxantrone, etoposide, and cytarabine (PSC-MEC). Adv Exp Med Biol. 1999,457:47–56. Fisher GA, Lum BL, Hausdorff J, Sikic BI. Pharmacological considerations in the modulation of multidrug resistance. Eur J Cancer. 1996,32A(6):1082–1088. <h3>Acknowledgements</h3> We thank prof. Guofeng GAO9s assistance in editing the manuscript. <h3>Disclosure of Interest</h3> M. Wang Grant/research support from: NO, P. ZENG Consultant for: NO, G. ZHOU Employee of: NO, J. LV Paid instructor for: NO, Q. WANG Grant/research support from: NO, Speakers bureau: NO