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THU0238 P-glycoprotein monoclonal antibody improves lupus-like syndrome in MRL/LPR mice
  1. M Wang,
  2. P Zeng,
  3. G Zhou,
  4. J Lv,
  5. Q Wang
  1. Department of Rheumatology and Immunology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, CHINA., Shenzhen, China

Abstract

Background Preventing steroid resistance and maintaining disease control are significant challenges to overcome in treating SLE patients[1]. 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[2].Inhibition of P-gp could overcome such drug resistance[3,4]. So we observed the effect of P-gp monoclonal antibody on MRL/lpr lupus mice.

Table 1.

Effects of P-gp monoclonal antibody on the levels of anti-dsDNA antibodies, serum creatinine and the routine blood test of MRL/lpr mice ('X±s)

Objectives To investigate the efficacy of P-glycoprotein monoclonal antibody in the treatment of the MRL/lpr mice.

Methods 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.

Results From the 22th week,the body weight of groups Gl and G2 increased significantly than that of the group G0 (p<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 (p<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 (p<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 (p<0.05). One week after treatment, the levels of anti-dsDNA antibodies in group Gl (43±19)x102 U/ml and G2 (45±32)x102 U/ml were both significantly decreased than those of the group G0 (87±39)x102 U/ml (p<0.05),and at the 26th weeks the difference between group G2 (35±11)xl02 U/ml and G0 (59±35)x102 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) (p<0.05), and that of group G2 was significantly less that of group Gl (p<0.05).

Conclusions P-glycoprotein monoclonal antibody is very effective in treating MRL/lpr mice.It is safe and free of rejection reactions.

References

  1. Barnes PJ.Mechanisms and resistance in glucocorticoid control of inflammation. J Steroid Biochem Mol Biol. 2010,120(2–3):76–85.

  2. 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.

  3. 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.

  4. Fisher GA, Lum BL, Hausdorff J, Sikic BI. Pharmacological considerations in the modulation of multidrug resistance. Eur J Cancer. 1996,32A(6):1082–1088.

References

Acknowledgements We thank prof. Guofeng GAO's assistance in editing the manuscript.

Disclosure of Interest 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

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