Increased circulating transforming growth factor β1 in a patient with giant hepatic hemangioma: Possible contribution to an impaired immune function

✍ Scribed by N. Ito; S. Kawata; H. Tsushima; S. Tamura; S. Kiso; S. Takami; T. Igura; M. Monnden; Y. Matsuzawa

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 524 KB
• Volume: 25
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510250117

✦ Synopsis

tumors, which was cancelled by anti-TGF-b 1 antibodies. 13 A patient, having a huge hepatic hemangioma, pre-

These findings indicate that the elevated concentration of sented with decreases in the number of peripheral lymcirculating TGF-b 1 may exert an imunosuppression in vivo. phocytes and in serum concentrations of g-globulin and

The authors describe in this study a case of giant hepatic immunoglobulin (Ig) G, and a negative purified protein hemangioma, associated with impaired humoral and cellular derivatives skin test, indicating that the patient's immuimmunity. This case showed marked elevation of plasma nity was impaired. The plasma concentration of trans-TGF-b 1 concentration. After the surgical removal of the hemforming growth factor b 1 (TGF-b 1 ), a potent immunosupangioma, the plasma TGF-b 1 concentration decreased markpressor, in the patient was markedly elevated (113 ng/ edly, and normal immune function was restored. These obser-mL, normal õ 5). After the surgical removal of the tumor, vations suggest that the elevated circulating TGF-b 1 may the plasma TGF-b 1 concentration decreased, and the pahave induced the impaired immunity in this case. tient's immunity was restored to normal. Northern blot analysis showed an overexpression of the TGF-b 1 gene PATIENTS AND METHODS in the hemangioma tissue, while normal control liver tissue expressed undetectable levels of TGF-b 1 messen-A 45-year-old woman was admitted to the Osaka University Hospital Liver Clinic (Osaka, Japan) for evaluation and treatment of a ger RNA. These results suggest that the elevated levels hepatic mass in October of 1993. Since April of 1993, postprandial of TGF-b 1 in the plasma were derived from the giant abdominal fullness had been noted. In September, the patient was hemangioma tissue and may have contributed to the imadmitted to a local hospital and was found to have a hepatic mass paired immune function in the patient. (HEPATOLOGY that was 6 cm in diameter, by abdominal ultrasonography. One 1997;25:93-96.)

month later, follow-up computed tomography revealed an increase in the size of the mass, which had grown to 10 cm in diameter; the patient was then referred to our hospital. She often complained of Hemangioma is a common benign tumor of the liver, the an increased susceptibility to upper respiratory infection and took a vast majority of which remain clinically silent. 1,2 However, cold remedy; however, she denied using oral contraceptives or other giant hepatic hemangioma, relatively rare in its incidence, drugs. On admission, the patient was afebrile and appeared well may present with clinical manifestations, such as abdominal nourished. Her abdomen was asymmetrically distended and a firm, swelling, pain, and symptoms referable to the gastrointestielastic, nontender liver mass was felt 12 cm below the right hypo- nal tract, due to compression or displacement of viscera. 3 chondria. Neck, axillary, and inguinal lymph nodes were not palpa- Less frequent complications include sudden pain due to ble.

Hematological examination showed neither anemia, thrombocyto-thrombosis within the hemangiomas, 4 acute abdominal crisis penia, nor leukocytopenia, but rather, a decrease in the number of due to spontaneous or traumatic rupture, 5 and bleeding tenperipheral lymphocytes (458/mm 3 ). Liver function tests were normal.

dency due to the depletion of platelets. 6 Other rare complica-Serum markers for viral hepatitis B, C, and tumor markers including tions have been reported, 7 but, to our knowledge, no patients in carcino-embryonic antigen, a-fetoprotein, and CA 19-9 were all have presented with associated impaired immunity. negative. Autoantibodies were not present. Serum levels of estron, Transforming growth factor b (TGF-b) belongs to a superestradiol, estriol, progesterone, and sex hormone-binding globulin family of structurally related regulatory proteins, including were all within normal limits. five isoforms of TGF-b, three of which (TGF-b 1 , -b 2 , and -b 3 ) Flow cytometric analysis showed a decrease in the B-cell (CD9 / are expressed in mammals. TGF-b is a potent immunomodulymphocyte) fraction (4.1%, normal; range, 13.4-21.8) and a relative increase of the T-cell (CD3 / lymphocyte) fraction (89.5%, normal;

lator in vitro that has been shown to suppress B-cell proliferarange, 68-81.8) indicating that the decrease in the number of periphtion, immunoglobulin secretion, 8,9 T-lymphocyte proliferaeral lymphocytes most likely resulted from a decrease in B lymphotion, 10 natural and lymphokine-activated killing by large cytes. CD4 / and CD8 / lymphocytes were 59.1% and 23.3% of the total granular lymphocytes, 11 and generation of cytotoxic T lymperipheral lymphocytes, respectively. Consistent with the decreased phocytes. 12 TGF-b 1 may also act as an immunosuppressor in number of B lymphocytes, the serum g-globulin concentration was vivo. It has been reported that natural killer activity was low (0.53 g/dL; 8.6% of total protein). Specifically, the serum immuno- suppressed in the mice bearing highly TGF-b 1 -producing globulin (Ig) G and IgA levels (748 mg/dL, normal; range, 1,000- 2,060, and 79 mg/dL, normal; range, 115-440, respectively) were decreased. The serum IgM level was slightly low but within the normal range (138 mg/dL, normal; range, 79-338). These data suggested that Abbreviations: Ig, immunoglobulin; TGF-b1, transforming growth factor b1; ELISA, en-the patient's humoral immunity was impaired. A purified protein zyme-linked immunosorbent assay. derivatives (PPD) skin test was negative at 48 hours, despite having From the