P-glycoprotein and drug resistance in systemic autoimmune diseases

International Journal of Molecular Sciences

Volumn 15, Issue 3, 2014, Pages 4965-4976

  Picchianti Diamanti, Andrea ^a   Rosado, Maria Manuela ^b   Scarsella, Marco ^b   Laganà, Bruno ^a   D'Amelio, Raffaele ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

Author keywords

Autoimmune diseases; Lymphocytes; Multidrug resistance; p glycoprotein

Indexed keywords

ABC TRANSPORTER; AZATHIOPRINE; BIOLOGICAL MARKER; BREAST CANCER RESISTANCE PROTEIN; CASPASE 3; CORTICOSTEROID; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; GLYCOPROTEIN P INHIBITOR; HYDROXYCHLOROQUINE; LEFLUNOMIDE; METHOTREXATE; MULTIDRUG RESISTANCE PROTEIN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; SALAZOSULFAPYRIDINE; TACROLIMUS; VENLAFAXINE; VERAPAMIL; CYCLOSPORIN; IMMUNOSUPPRESSIVE AGENT;

AUTOIMMUNE DISEASE; CANCER THERAPY; CELL MATURATION; CELL PROLIFERATION; CROHN DISEASE; FLOW CYTOMETRY; GENETIC POLYMORPHISM; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; IDIOPATHIC THROMBOCYTOPENIC PURPURA; IMMUNE RESPONSE; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; LYMPHOCYTE ACTIVATION; MIXED LYMPHOCYTE REACTION; MOLECULARLY TARGETED THERAPY; NONHUMAN; PROTEIN EXPRESSION; PSORIATIC ARTHRITIS; REGULATORY MECHANISM; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; TH17 CELL; ANTAGONISTS AND INHIBITORS; ARTHRITIS, PSORIATIC; ARTHRITIS, RHEUMATOID; DRUG EFFECTS; DRUG RESISTANCE; IMMUNOLOGY; LUPUS ERYTHEMATOSUS, SYSTEMIC;

ADRENAL CORTEX HORMONES; ARTHRITIS, PSORIATIC; ARTHRITIS, RHEUMATOID; CYCLOSPORINE; DRUG RESISTANCE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LUPUS ERYTHEMATOSUS, SYSTEMIC; P-GLYCOPROTEIN; TACROLIMUS;

EID: 84896448400     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms15034965     Document Type: Review

References (79)

1. Rosado, M.M.; Diamanti, A.P.; Capolunghi, F.; Carsetti, R. B cell modulation strategies in autoimmunity: The SLE example. Curr. Pharm. Des. 2011, 17, 3155-3165.
2. Radstake, T.R.; Svenson, M.; Eijsbouts, A.M.; van den Hoogen, F.H.; Enevold, C.; van Riel, P.L.; Bendtzen, K. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann. Rheum. Dis. 2009, 68, 1739-1745.
3. Ramesh, R.; Kozhaya, L.; McKevitt, K.; Djuretic, I.M.; Carlson, T.J.; Quintero, M.A.; McCauley, J.L.; Abreu, M.T.; Unutmaz, D.; Sundrud, M.S. Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J. Exp. Med. 2014, 211, 89-104.
4. Dean, M.; Rzhetsky, A.; Allikmets, R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001, 11, 1156-1166.
5. Gottesman, M.M.; Pastan, I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 1993, 62, 385-427.
6. Aouali, N.; Eddabra, L.; Macadre, J.; Morjani, H. Immunosuppressors and reversion of multidrug-resistance. Crit. Rev. Oncol. Hematol. 2005, 56, 61-70.
7. Diaz-Borjon, A.; Richaud-Patin, Y.; Alvarado de la Barrera, C.; Jakez-Ocampo, J.; Ruiz-Arguelles, A.; Llorente, L. Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part II: Increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control. Jt. Bone Spine 2000, 67, 40-48.
8. Van de Ven, R.; Oerlemans, R.; van der Heijden, J.W.; Scheffer, G.L.; de Gruijl, T.D.; Jansen, G.; Scheper, R.J. ABC drug transporters and immunity: Novel therapeutic targets in autoimmunity and cancer. J. Leukoc. Biol. 2009, 86, 1075-1087.
9. Ambudkar, S.V.; Dey, S.; Hrycyna, C.A.; Ramachandra, M.; Pastan, I.; Gottesman, M.M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 1999, 39, 361-398.
10. Drach, J.; Gsur, A.; Hamilton, G.; Zhao, S.; Angerler, J.; Fiegl, M.; Zojer, N.; Raderer, M.; Haberl, I.; Andreeff, M.; et al. Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-γ in normal human T lymphocytes. Blood 1996, 88, 1747-1754.
11. Randolph, G.J.; Beaulieu, S.; Pope, M.; Sugawara, I.; Hoffman, L.; Steinman, R.M.; Muller, W.A. A physiologic function for P-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels. Proc. Natl. Acad. Sci. USA 1998, 95, 6924-6929.
12. Zhang, J.; Alston, M.A.; Huang, H.; Rabin, R.L. Human T cell cytokine responses are dependent on multidrug resistance protein-1. Int. Immunol. 2006, 18, 485-493.
13. Smit, J.J.; Schinkel, A.H.; Mol, C.A.; Majoor, D.; Mooi, W.J.; Jongsma, A.P.; Lincke, C.R.; Borst, P. Tissue distribution of the human MDR3 P-glycoprotein. Lab. Investig. 1994, 71, 638-649.
14. Wang, Y.; Hao, D.; Stein, W.D.; Yang, L. A kinetic study of rhodamine123 pumping by P-glycoprotein. Biochim. Biophys. Acta 2006, 1758, 1671-1676.
15. Bommhardt, U.; Cerottini, J.C.; MacDonald, H.R. Heterogeneity in P-glycoprotein (multidrug resistance) activity among murine peripheral T cells: Correlation with surface phenotype and effector function. Eur. J. Immunol. 1994, 24, 2974-2981.
16. Kyle-Cezar, F.; Echevarria-Lima, J.; dos Santos Goldenberg, R.C.; Rumjanek, V.M. Expression of c-kit and Sca-1 and their relationship with multidrug resistance protein 1 in mouse bone marrow mononuclear cells. Immunology 2007, 121, 122-128.
17. MacDonald, H.R.; Bommhardt, U.; Cerottini, J.C. Developmentally regulated expression of P-glycoprotein (multidrug resistance) activity in mouse thymocytes. Eur. J. Immunol. 1995, 25, 1457-1460.
18. Robbiani, D.F.; Finch, R.A.; Jager, D.; Muller, W.A.; Sartorelli, A.C.; Randolph, G.J. The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3β, ELC)-dependent mobilization of dendritic cells to lymph nodes. Cell 2000, 103, 757-768.
19. Lee, J.S.; Jung, I.D.; Lee, C.-M.; Noh, K.T.; Park, J.W.; Son, K.H.; Heo, D.R.; Shin, Y.K.; Kim, D.; Park, Y.-M. Venlafaxine inhibits the development and differentiation of dendritic cells through the regulation of P-glycoprotein. Int. Immunopharmacol. 2011, 11, 1348-1357.
20. Schinkel, A.H.; Smit, J.J.; van Tellingen, O.; Beijnen, J.H.; Wagenaar, E.; van Deemter, L.; Mol, C.A.A.M.; van der Valk, M.A.; Robanus-Maandag, E.C.; te Riele, H.P.J.; et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994, 77, 491-502.
21. Smit, J.J.M.; Schinkel, A.H.; Oude Elferink R.P.J.; Groen, A.K.; Wagenaar, E.; van Deemter, L.; Mol, C.A.A.M.; Ottenhoff, R.; van der Lugt, N.M.T.; van Roon, M.A.; et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 1993, 75, 451-462.
22. Maggio-Price, L.; Bielefeldt-Ohmann, H.; Treuting, P.; Iritani, B.M.; Zeng, W.; Nicks, A.; Tsang, M.; Shows, D.; Morrissey, P.; Viney, J.L. Dual infection with Helicobacter bilis and Helicobacter hepaticus in P-glycoprotein-deficient mdr1a (-/-) mice results in colitis that progresses to dysplasia. Am. J. Pathol. 2005, 166, 1793-1806.
23. Panwala, C.M.; Jones, J.C.; Viney, J.L. A novel model of inflammatory bowel disease: Mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J. Immunol. 1998, 161, 5733-5744.
24. Campbell, D.J.; Koch, M.A. Phenotypical and functional specialization of Foxp3+ regulatory T cells. Nat. Rev. Immunol. 2011, 11, 119-130.
25. Feuerer, M.; Hill, J.A.; Mathis, D.; Benoist, C. Foxp3+ regulatory T cells: Differentiation, specification, subphenotypes. Nat. Immunol. 2009, 10, 689-695.
26. Kim, J.M.; Rasmussen, J.P.; Rudensky, A.Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 2007, 8, 191-197.
27. Sakaguchi, S. Naturally arising Foxp3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 2005, 6, 345-352.
28. Tanner, S.M.; Staley, E.M.; Lorenz, R.G. Altered generation of induced regulatory T cells in the FVB mdr1a (-/-) mouse model of colitis. Mucosal Immunol. 2013, 6, 309-323.
29. Chaudhary, P.M.; Roninson, I.B. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 1991, 66, 85-94.
30. Haraguchi, S.; Ho, S.K.; Morrow, M.; Goodenow, M.M.; Sleasman, J.W. Developmental regulation of P-glycoprotein activity within thymocytes results in increased anti-HIV protease inhibitor activity. J. Leukoc. Biol. 2010, 90, 653-660.
31. Pilarski, L.M.; Paine, D.; McElhaney, J.E.; Cass, C.E.; Belch, A.R. Multidrug transporter P-glycoprotein 170 as a differentiation antigen on normal human lymphocytes and thymocytes: Modulation with differentiation stage and during aging. Am. J. Hematol. 1995, 49, 323-335.
32. Chaudhary, P.M.; Mechetner, E.B.; Roninson, I.B. Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes. Blood 1992, 80, 2735-2739.
33. Drach, D.; Zhao, S.; Drach, J.; Mahadevia, R.; Gattringer, C.; Huber, H.; Andreeff, M. Subpopulations of normal peripheral blood and bone marrow cells express a functional multidrug resistant phenotype. Blood 1992, 80, 2729-2734.
34. Klimecki, W.T.; Futscher, B.W.; Grogan, T.M.; Dalton, W.S. P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 1994, 83, 2451-2458.
35. Meaden, E.R.; Hoggard, P.G.; Khoo, S.H.; Back, D.J. Determination of P-gp and MRP1 expression and function in peripheral blood mononuclear cells in vivo. J. Immunol. Methods 2002, 262, 159-165.
36. Lee, J.S.; Paull, K.; Alvarez, M.; Hose, C.; Monks, A.; Grever, M.; Fojo, A.T.; Bates, S.E. Rhodamine efflux patterns predict P-glycoprotein substrates in the National Cancer Institute drug screen. Mol. Pharmacol. 1994, 46, 627-638.
37. Gottesman, M.M.; Fojo, T.; Bates, S.E. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat. Rev. Cancer 2002, 2, 48-58.
38. Smyth, M.J.; Krasovskis, E.; Sutton, V.R.; Johnstone, R.W. The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis. Proc. Natl. Acad. Sci. USA 1998, 95, 7024-7029.
39. Jones, K.; Bray, P.G.; Khoo, S.H.; Davey, R.A.; Meaden, E.R.; Ward, S.A.; Back, D.J. P-Glycoprotein and transporter MRP1 reduce HIV protease inhibitor uptake in CD4 cells: Potential for accelerated viral drug resistance? AIDS 2001, 15, 1353-1358.
40. Tempestilli, M.; Gentilotti, E.; Tommasi, C.; Nicastri, E.; Martini, F.; de Nardo, P.; Narciso, P.; Pucillo, L.P. Determination of P-glycoprotein surface expression and functional ability after in vitro treatment with darunavir or raltegravir in lymphocytes of healthy donors. Int. Immunopharmacol. 2011, 16, 492-497.
41. Tsujimura, S.; Saito, K.; Nakayamada, S.; Tanaka, Y. Relevance of multidrug resistance 1 and P-glycoprotein to drug resistance in patients with systemic lupus erythematosus. Histol. Histopathol. 2007, 22, 465-468.
42. Ho, G.T.; Soranzo, N.; Nimmo, E.R.; Tenesa, A.; Goldstein, D.B.; Satsangi, J. ABCB1/MDR1 gene determines susceptibility and phenotype in ulcerative colitis: Discrimination of critical variants using a gene-wide haplotype tagging approach. Hum. Mol. Genet. 2006, 15, 797-805.
43. Littman, D.R.; Rudensky, A.Y. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010, 140, 845-858.
44. Tan, E.M.; Cohen, A.S.; Fries, J.F.; Masi, A.T.; Mcshane, D.J.; Rothfield, N.F.; Schaller, J.G.; Talal, N.; Winchester, R.J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheumatol. 1982, 25, 1271-1277.
45. D'Cruz, D.P.; Khamashta, M.A.; Hughes, G.R. Systemic lupus erythematosus. Lancet 2007, 369, 587-596.
46. Bertoli, A.M.; Vila, L.M.; Reveille, J.D.; Alarcon, G.S. Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: Disease expression and outcome in acute onset lupus. Ann. Rheum. Dis. 2008, 67, 500-504.
47. Ioannou, Y.; Isenberg, D.A. Current concepts for the management of systemic lupus erythematosus in adults: A therapeutic challenge. Postgrad. Med. J. 2002, 78, 599-606.
48. Miescher, P.A.; Favre, H.; Lemoine, R.; Huang, Y.P. Drug combination therapy of systemic lupus erythematosus. Semin. Immunopathol. 1994, 16, 295-311.
49. Isenberg, D.A.; Snaith, M.L.; Morrow, W.J.; Al-Khader, A.A.; Cohen, S.L.; Fisher, C.; Mowbray, J. Cyclosporin A for the treatment of systemic lupus erythematosus. Int. J. Immunopharmacol. 1981, 3, 163-169.
50. Germano, V.; Picchianti Diamanti, A.; Ferlito, C.; Podesta, E.; Salemi, S.; Migliore, A.; D'Amelio, R.; Lagana, B. Cyclosporine A in the long-term management of systemic lupus erythematosus. J. Biol. Regul. Homeost. Agents 2011, 25, 397-403.
51. Caccavo, D.; Lagana, B.; Mitterhofer, A.P.; Ferri, G.M.; Afeltra, A.; Amoroso, A.; Bonomo, L. Long-term treatment of systemic lupus erythematosus with cyclosporin A. Arthritis Rheumatol. 1997, 40, 27-35.
52. Picchianti Diamanti, A.; Germano, V.; Ferlito, C.; Migliore, A.; D'Amelio, R.; Lagana, B. Health-related quality of life and disability in patients with rheumatoid, early rheumatoid and early psoriatic arthritis treated with etanercept. Qual. Life Res. 2010, 19, 821-826.
53. Smolen, J.S.; Landewe, R.; Breedveld, F.C.; Dougados, M.; Emery, P.; Gaujoux-Viala, C.; Gorter, S.; Knevel, R.; Nam, J.; Schoels, M. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann. Rheum. Dis. 2010, 69, 964-975.
54. Van der Heijden, J.W.; Dijkmans, B.A.; Scheper, R.J.; Jansen, G. Drug insight: Resistance to methotrexate and other disease-modifying antirheumatic drugs-From bench to bedside. Nat. Clin. Pract. Rheumatol. 2007, 3, 26-34.
55. Day, R. Adverse reactions to TNF-α inhibitors in rheumatoid arthritis. Lancet 2002, 359, 540-541.
56. Fraser, A.D.; van Kuijk, A.W.; Westhovens, R.; Karim, Z.; Wakefield, R.; Gerards, A.H.; Landwew, R.; Steinfeld, S.D.; Emery, P.; Dijkmans, B.A.C.; et al. A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis. Ann. Rheum. Dis. 2005, 64, 859-864.
57. Mazzanti, G.; Coloni, L.; de Sabbata, G.; Paladini, G. Methotrexate and cyclosporin combined therapy in severe psoriatic arthritis. A pilot study. Acta Derm. Venereol. Suppl. 1994, 186, 116-117.
58. Migliore, A.; Bizzi, E.; Massafra, U.; Vacca, F.; Martin, L.S.; Ferlito, C.; Podesta, E.; Granata, M.; Lagana, B. Can Cyclosporine-A associated to methotrexate maintain remission induced by anti-TNF agents in rheumatoid arthritis patients? (Cynar pilot study). Int. J. Immunopathol. Pharmacol. 2010, 23, 783-790.
59. Maillefert, J.F.; Maynadie, M.; Tebib, J.G.; Aho, S.; Walker, P.; Chatard, C.; Dulieu, V.; Bouvier, M.; Carli, P.M.; Tavernier, C. Expression of the multidrug resistance glycoprotein 170 in the peripheral blood lymphocytes of rheumatoid arthritis patients. The percentage of lymphocytes expressing glycoprotein 170 is increased in patients treated with prednisolone. Br. J. Rheumatol. 1996, 35, 430-435.
60. Yudoh, K.; Matsuno, H.; Nakazawa, F.; Yonezawa, T.; Kimura, T. Increased expression of multidrug resistance of P-glycoprotein on Th1 cells correlates with drug resistance in rheumatoid arthritis. Arthritis Rheumatol. 1999, 42, 2014-2015.
61. Hider, S.L.; Owen, A.; Hartkoorn, R.; Khoo, S.; Back, D.; Silman, A.J.; Bruce, I.N. Down regulation of multidrug resistance protein-1 expression in patients with early rheumatoid arthritis exposed to methotrexate as a first disease-modifying antirheumatic drug. Ann. Rheum. Dis. 2006, 65, 1390-1393.
62. Tsujimura, S.; Saito, K.; Nawata, M.; Nakayamada, S.; Tanaka, Y. Overcoming drug resistance induced by P-glycoprotein on lymphocytes in patients with refractory rheumatoid arthritis. Ann. Rheum. Dis. 2008, 67, 380-388.
63. Tsujimura, S.; Saito, K.; Nakayamada, S.; Tanaka, Y. Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients with intractable rheumatoid arthritis. Mod. Rheumatol. 2010, 20, 139-146.
64. Agarwal, V.; Mittal, S.K.; Misra, R. Expression of multidrug resistance-1 protein correlates with disease activity rather than the refractoriness to methotrexate therapy in rheumatoid arthritis. Clin. Rheumatol. 2009, 28, 427-433.
65. Suzuki, K.; Saito, K.; Tsujimura, S.; Nakayamada, S.; Yamaoka, K.; Sawamukai, N.; Iwata, S.; Nawata, M.; Nakano, K.; Tanaka, Y. Tacrolimus, a calcineurin inhibitor, overcomes treatment unresponsiveness mediated by P-glycoprotein on lymphocytes in refractory rheumatoid arthritis. J. Rheumatol. 2010, 37, 512-520.
66. Choe, J.Y.; Park, K.Y.; Park, S.H.; Lee, S.I.; Kim, S.K. Regulatory effect of calcineurin inhibitor, tacrolimus, on IL-6/sIL-6R-mediated RANKL expression through JAK2-STAT3-SOCS3 signaling pathway in fibroblast-like synoviocytes. Arthritis Res. Ther. 2013, 15, R26:1-R26:12.
67. Kang, K.Y.; Ju, J.H.; Song, Y.W.; Yoo, D.H.; Kim, H.Y.; Park, S.H. Tacrolimus treatment increases bone formation in patients with rheumatoid arthritis. Rheumatol. Int. 2013, 33, 2159-2163.
68. Kis, E.; Nagy, T.; Jani, M.; Molnar, E.; Janossy, J.; Ujhellyi, O.; Nemet, K.; Heredi-Szabo, K.; Krajcsi, P. Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: Implications for drug resistance. Ann. Rheum. Dis. 2009, 68, 1201-1207.
69. Picchianti Diamanti, A.; Rosado, M.; Germano, V.; Scarsella, M.; Giorda, E.; Podesta, E.; D'Amelio, R.; Carsetti, R.; Lagana, B. Reversion of resistance to immunosuppressive agents in three patients with psoriatic arthritis by cyclosporine A: Modulation of P-glycoprotein function. Clin. Immunol. 2010, 138, 9-13.
70. Llorente, L.; Richaud-Patin, Y.; Diaz-Borjon, A.; Alvarado de la Barrera, C.; Jakez-Ocampo, J.; de la Fuente, H.; Gonzalez-Amaro, R.; Diaz-Jouanen, E. Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part I: Increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcome. Jt. Bone Spine 2000, 67, 30-39.
71. Tsujimura, S.; Saito, K.; Nakayamada, S.; Nakano, K.; Tanaka, Y. Clinical relevance of the expression of P-glycoprotein on peripheral blood lymphocytes to steroid resistance in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2005, 52, 1676-1683.
72. Henmi, K.; Yoshida, M.; Yoshikawa, N.; Hirano, T. P-glycoprotein functions in peripheral-blood CD4+ cells of patients with systemic lupus erythematosus. Biol. Pharm. Bull. 2008, 31, 873-878.
73. Zhang, B.; Shi, Y.; Lei, T.C. Detection of active P-glycoprotein in systemic lupus erythematosus patients with poor disease control. Exp. Ther. Med. 2012, 4, 705-710.
74. Levy, A.S.; Cunningham-Rundles, S.; Mazza, B.; Simm, M.; Gorlick, R.; Bussel, J. High P-glycoprotein-mediated export observed in patients with a history of idiopathic thrombocytopenic purpura. Br. J. Haematol. 2002, 118, 836-838.
75. Lopez-Karpovitch, X.; Graue, G.; Crespo-Solis, E.; Piedras, J. Multidrug resistance-1 in T lymphocytes and natural killer cells of adults with idiopathic thrombocytopenic purpura: Effect of prednisone treatment. Arch. Med. Res. 2008, 39, 541-545.
76. Ruiz-Soto, R.; Richaud-Patin, Y.; Lopez-Karpovitch, X.; Llorente, L. Multidrug resistance-1 (MDR-1) in autoimmune disorders III: Increased P-glycoprotein activity in lymphocytes from immune thrombocytopenic purpura patients. Exp. Hematol. 2003, 31, 483-487.
77. De Iudicibus, S.; Franca, R.; Martelossi, S.; Ventura, A.; Decorti, G. Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease. World J. Gastroenterol. 2011, 17, 1095-1108.
78. Potocnik, U.; Ferkolj, I.; Glavac, D.; Dean, M. Polymorphisms in multidrug resistance 1 (MDR-1) gene are associated with refractory Crohn's disease and ulcerative colitis. Genes Immun. 2004, 5, 530-539.
79. Cucchiara, S.; Latiano, A.; Palmieri, O.; Canani, R.B.; D'Inca, R.; Guariso, G.; Vieni, G.; de Venuto, D.; Riegler, G.; de'Angelis, G.L. Polymorphisms of tumor necrosis factor-α but not MDR-1 influence response to medical therapy in pediatric-onset inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr. 2007, 44, 171-179.