ABSTRACT
We herein describe the case of a 60-year-old man with a history of Behçet's disease and myelodysplastic syndrome who received cord blood transplantation (CBT). The patient was given anti-thymocyte globulin conditioning and tacrolimus to prevent graft-versus-host disease. Two months after CBT, his blood Tac concentration measured by an antibody-conjugated magnetic immunoassay (ACMIA) was found to have increased >4-fold, even after the Tac treatment was stopped. This false response was caused by the interference of endogenous heterophilic antibodies with ACMIA. Therefore, physicians must be aware of possible false ACMIA results for patients with a history of autoimmune disease and/or treated by xenogeneic antibody therapy.
Subject(s)
Cyclosporine/administration & dosage , Graft vs Host Disease/prevention & control , Immunosuppressive Agents/administration & dosage , Myelodysplastic Syndromes/therapy , Tacrolimus/administration & dosage , Behcet Syndrome/epidemiology , Cord Blood Stem Cell Transplantation , False Positive Reactions , Humans , Immunoassay , Male , Middle Aged , Myelodysplastic Syndromes/epidemiologyABSTRACT
The antibiotic thiazole compound siomycin, which we have found from the culture broth of Actinomycetes (strain No.806097) in search of antibody production inhibitor, showed the in vitro immunosuppressive property against B-cells stimulated with T-cell independent antigen DNP-LPS (dinitrophenyl-lipopolysaccharide) while it also showed inhibitory effect against T-cell proliferation. Its inhibitory mechanism was considered to be different from that of FK506, the representative of T-cell immunosuppressant. Moreover, siomycin showed inhibitory effect in both T-cell dependent and independent murine antibody production models and decreased the severity in murine collagen arthritis model. Therefore, siomycin is a unique immunosuppressant which has potential for the treatment of some antibody-mediated diseases.
Subject(s)
Antibody Formation/drug effects , Arthritis, Experimental/drug therapy , Immunosuppressive Agents/pharmacology , Lymphocyte Activation/drug effects , Peptides/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , B-Lymphocytes/immunology , Collagen , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Mice , Mice, Inbred BALB C , Mice, Inbred DBA , Peptides/therapeutic use , T-Lymphocytes/immunology , Tacrolimus/pharmacology , Tacrolimus/therapeutic use , Thiostrepton/pharmacology , Thiostrepton/therapeutic useABSTRACT
A cyclic tetrapeptide FR235222, a novel immunosuppressant, has been isolated from the fermentation broth of a fungus, Acremonium sp. No. 27082. FR235222 showed potent and selective inhibitory effects on both T cell proliferation and lymphokine production. Further study has revealed this compound exhibits potent inhibitory effects on the activity of mammalian histone deacetylases (HDACs).
Subject(s)
Acremonium/metabolism , Enzyme Inhibitors/isolation & purification , Histone Deacetylase Inhibitors , Immunosuppressive Agents/isolation & purification , Peptides, Cyclic/isolation & purification , Acremonium/chemistry , Acremonium/classification , Acremonium/immunology , Animals , Enzyme Inhibitors/immunology , Enzyme Inhibitors/pharmacology , Female , Fermentation , Hepatocytes/drug effects , Hepatocytes/immunology , Immunosuppressive Agents/immunology , Immunosuppressive Agents/pharmacology , Interleukin-2/immunology , Interleukin-2/metabolism , Interleukin-4/immunology , Interleukin-4/metabolism , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Lymphocyte Culture Test, Mixed , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude , Peptides, Cyclic/immunology , Peptides, Cyclic/pharmacology , Rats , Soil Microbiology , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , T-Lymphocytes/immunologyABSTRACT
FR235222, a novel immunosuppressant which possesses potent inhibitory effects on the activity of mammalian histone deacetylases (HDACs), has been isolated from the fermentation broth of a fungus, Acremonium sp. No. 27082. FR235222 exhibited marked immunosuppressive effects on mouse ex vivo splenic T-lymphocyte proliferation, mouse delayed type hypersensitivity (DTH) response, rat adjuvant-induced arthritis (AA) and rat heterotopic cardiac transplantation. These results showed potential clinical use of this compound as a new type immunosuppressant in the fields of autoimmune diseases and organ transplantations.
