Severe aplastic anemia with autoimmune thyroiditis showing no hematological response to intensive immunosuppressive therapy.
A 39-year-old woman with severe aplastic anemia (SAA) was transferred to our institution. She also had autoimmune thyroiditis with several positive autoantibodies. Clonal or oligoclonal T-cell proliferation was demonstrated by determining the size distribution of the complementarity-determining region 3 (CDR3) of T-cell receptor beta-chain (TCR-Vbeta) subfamilies in the patient's bone marrow and peripheral blood cells. The results suggested that hematopoiesis was suppressed by immune-mediated mechanisms. Immunosuppressive therapy for SAA using cyclosporin A (CsA) alone or concurrent CsA and antithymocyte globulin (ATG) failed to induce a hematological response. The intensity of the autoantibodies, however, partially decreased during this period. In addition, the CD4/CD8 ratio was inverted after immunosuppressive therapy. These observations indicate that, in a subset of SAA, immune-mediated hematopoietic suppression cannot be successfully treated by conventional immunosuppressive therapy, even though a substantial improvement in the underlying immunological changes can be achieved. Other therapies such as hematopoietic stem cell transplantation or more intensified repeated ATG therapy may be necessary for such patients.
Tomonari
Akira
A
Department of Hematology/Oncology, Institute of Medical Science, University of Tokyo, Japan. atomonar@ims.u-tokyo.ac.jp
Tojo
Arinobu
A
Iseki
Tohru
T
Ooi
Jun
J
Hase
Hidenori
H
Shirafuji
Naoki
N
Tani
Kenzaburo
K
Asano
Shigetaka
S
D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood; D017252:CD3 Complex / Q000032:analysis; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D022801:Complementarity Determining Regions / Q000032:analysis; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016131:Lymphocyte Subsets; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D017211:Treatment Failure
D000961:Antilymphocyte Serum; D001323:Autoantibodies; D017252:CD3 Complex; D022801:Complementarity Determining Regions; D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine