Study on diagnosis developmental mechanism of transfusion-associated GVHD by analysis of DNA polymorphism

Research Project

Project/Area Number	04454315
Research Category	Grant-in-Aid for General Scientific Research (B)
Allocation Type	Single-year Grants
Research Field	General surgery
Research Institution	KYOTO UNIVERSITY
Principal Investigator	ITO Kazuhiko Kyoto University Hospital, Department of Transfusion Medicine, Professor, 医学部, 教授 (50034640)
Co-Investigator(Kenkyū-buntansha)	YOSHIDA Hisahiro Kyoto University Hospital, Department of Transfusion Medicine, Instructor, 医学部, 助手 (30135587)
Project Period (FY)	1992 – 1993
Project Status	Completed (Fiscal Year 1993)
Budget Amount *help	¥6,600,000 (Direct Cost: ¥6,600,000) Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000) Fiscal Year 1992: ¥5,000,000 (Direct Cost: ¥5,000,000)
Keywords	Transfusion-associated GVHD (TA-GVHD) / Immunodeficiency / HLA homozygote / HLA heterozygote / Chimera / DNA polymorphism / Transfusion / Microsatellite gene / 重症免疫不全 / HLA型 / リンパ球 / 多形性分析法 / 血液放射線照射 / PCR / 個人識別
Research Abstract	Transfusion-associated GVHD (TA-GVHD) develops in immunocompromized and immmunocompetent patients. When a recipient of HLA hetrozygote (a/b) is transfused with blood from a donor of HLA homozygote (a/a), a/b recognizes a/a as self and does not reject it but a/a recognizes a/b as nonself and damages it. Such a combination occurs 1/900 among unrelated Japanese and 1/100 between Japanese parents and children because the Japanese are relatively genetically homogeneous. However, the number of cases reported as TA-GVHD is lower than the estimated values. There is a possibility that patients with TA-GVHD have not been diagnozed truly and were overlooked. A new useful method for the diagnosis of TA-GVHD is DNA polymorphism detected by the length of microsatellite genes. DNA polymorphism of a patient's circulating lymphocytes is compared with that of his nail which is clearly his own self. Case 1 developed the typical symptoms of TA-GVHD after surgery of A-C bypass of heart with blood transfusion. Chimera was demonstrated in DNA polymorphism. Case 2 of acute promyerocytic leukemia was transfused frequently, developed doubtful symptoms of TA-GVHD and died. Change of DNA polymorphism was not demonstrated by repeated examination with circulating lymphocytes. Nail was not available. Case 3 developed doubtful symptoms of TA-GVHD after delivery with blood transfusion for bleeding. Chimera was not demonstrated in DNA polymorphism. The HLA phenotype of circulating lymphocytes was heterozygous. TA-GVHD was denied. The patient got well. Case 4 developed the typical symptoms of TA-GVHD after surgery of cystic cancer with blood transfusion. Chimera was not demonstrated in DNA polymorphism. The HLA phenotype of circulating lymphocytes was heterozygous. The symptom disappeared gradually after postperative day 14. The patient got well. The symptom may be due to drug allergy. Examination of DNA polymorphism is a strong means for the diagnosis of TA-GVHD.