title: Combined standard and novel immunosuppressive substances affect B-lymphocyte function.
abstract: A considerable fraction of renal transplanted patients is susceptible to humoral rejection. Today well-established therapy regimens are available to control antibody-mediated rejection in the short term. Nevertheless, donor-specific antibodies persist and graft function deteriorates over time. This might be due to insufficient maintenance immunosuppression - which always consists of two to three drugs with different mechanisms of action. Since T- and B-cell functions always depend on each other in the alloimmune response it is of interest to analyze the effects of combined standard and new immunosuppressive substances with T-cell inhibitory properties on B-cell function. The effectiveness of complementary administrations of sotrastaurin, mycophenolic acid and everolimus on the activation and function of human primary B-lymphocytes was tested. Everolimus and mycophenolic acid alone and in combination proved to be highly effective in suppressing B-cell activation, whereas the proteinkinase C inhibitor sotrastaurin had an unexpected and reverse impact on various B-cell functions when applied in combination with the mammalian target of rapamycin and the inosine monophosphate dehydrogenase inhibitor.
authors.affiliation: Department of Nephrology, Universitätsmedizin Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany. mareen.matz@charite.de
authors.forename: Mareen
authors.initials: M
authors.lastname: Matz
authors.forename: Martin
authors.initials: M
authors.lastname: Lehnert
authors.forename: Christine
authors.initials: C
authors.lastname: Lorkowski
authors.forename: Katharina
authors.initials: K
authors.lastname: Fabritius
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Weber
authors.forename: Mir-Farzin
authors.initials: MF
authors.lastname: Mashreghi
authors.forename: Hans-H
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000068338:Everolimus; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods / Q000592:standards*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D061251:Primary Cell Culture; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018122:B7-1 Antigen; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011758:Pyrroles; D011799:Quinazolines; C543528:sotrastaurin; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus