Multidrug resistance in heart transplant patients: a preliminary communication on a possible mechanism of therapy-resistant rejection.
Multidrug resistance refers to a complex cellular phenotype, the hallmark of which is cross-resistance to multiple drugs, for example, chemotherapeutic agents, that are unrelated to the selecting agent in structure, cellular target, and mode of action. The expression of this multidrug resistance is connected with the overexpression of P-glycoprotein. By applying the method of immunocytochemical assay, we have demonstrated the appearance of the multidrug-resistant phenotype (P-glycoprotein+ cells, multidrug-resistant cells) in mononuclear cells of the peripheral blood from 32/49 patients receiving triple-drug (azathioprine, steroids, cyclosporine) immunosuppressive therapy after heart transplantation. In the group of patients showing not only the presence of cells with multidrug-resistant phenotype in the peripheral blood, but also a significant increase in the number of these cells during the interval of observation (0 to 767 days)-16/32/49 cases--a significantly increased incidence of acute rejection episodes could be demonstrated. This supports the hypothesis of a possible existence of a therapy-resistant form of acute rejection, with an involvement of mechanisms of multidrug-resistance playing a role in its causal development.
Institute of Pathology, Hannover Medical School, Lower Saxony, Federal Republic of Germany.
J
J
Kemnitz
A
A
Uysal
A
A
Haverich
B
B
Heublein
T R
TR
Cohnert
W
W
Stangel
A
A
Georgii
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage; D003524:Cyclosporins / Q000008:administration & dosage; D004351:Drug Resistance / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D001379:Azathioprine; D008775:Methylprednisolone