Brettschneider, L

Kashiwagi, N

Penn, I

Porter, KA

Starzl, TE

English

D-Scholarship@Pitt

STUDIES OF HOMOGRAFT SEX AND OF GAMMA GLOBULIN PHENOTYPES AFTER ORTHOTOPIC HOMOTRANSPLANATION OF THE HUMAN LIVER NOBORU KASHIWAGI, M.D., K. A. PORTER, M.D., D.Sc., I. PENN, M.D., LAWRENCE BRETTSCHNEIDER, M.D. AND THOMAS E. STARZL, M.D., F.A.C.S. IT HAS BEEN ESTABLISHED that several serum proteins synthesized ex-clusively by the liver convert in the recipient to the phenotype spe-cificity of the original donor following orthotopic liver transplanta-tion (1, 2, 3). In this study the gamma G globulins (IgG) which are normally thought to be nonhepatic in origin were examined in 10 human recipients of replacement livers. When it was unexpectedly found that the Gm types of the donor were transmitted to the re-cipient, histopathologic studies of the livers were carried out to deter-mine their source. METHODS Phenotypes Gm [1, 2, and 12] were identified with the hemagglu-tination-inhibition test of Martensson (4). The only modification (5) was preliminary heating of the patient sera for 10 min. at 63° C. to inactivate rheumatoid factors (anti-IgG antibodies) which were pres-ent in 6 of the 10 recipients before transplantation and in all 10 after-wards. Lymphoid tissue transplanted with the human hepatic homografts was examined postoperatively in 12 patients. In addition nine liver homografts from male donors were analyzed by the technique of Barr (6) 12 hr. to 400 days after they had been placed into female re-cipients. With this method the nuclei of female cells contain a dis-tinctive chromatin mass. The sex was determined of the graft Kupffer cells and of the hepatic arterial and portal venous endothelial cells (7). RESULTS Gm Types: In 5 of the 10 patients the presence or absence of the Gm types [1, 2, and 12] was determined without efforts at quantita-tion, before transplantation, and on· a single occasion from 1 to 25 days later. In every instance all three of the phenotypes were found whether or not these had previously been present in the donor or the recipient. The indiscriminate conversion of the gamma G globulin From the Department of Surgery, University of Colorado Medical Center and the Veterans Administration Hospital, Denver and the Department of Pathology, St. Mary's Hospital and Medical School, London, England. Supported by U.S. Public Health Service grants AM-06344, AM-0777Z, FR-0005I, AI-0415Z, FR-00069, AM-IZ148, and AI-AM-08898. types was thought to be an artefact from multiple blood transfusions during and immediately after operation. In the other five recipients of six homografts, quantitative studies (Gm titers) were carried out serially for 60 days to almost one year. The new Gm types apparently caused by transfusion, tended to die out within 1 to 2 months, making it possible thereafter to trace the fate of the preexisting Gm profiles of the donors and recipients. In 3 of the 6 sets of observations the donor did not have one or more of the Gm phenotypes which were in the recipient. In the late follow-ups the previously present Gm types of the recipients remained the same during periods of six months to almost a year; new types were not added. In the other three patients with serial studies, the situation was the converse in that the donors each had one Gm type not naturally found in the recipient. During follow-ups of 60 to 326 days, these phenotypes could now be detected in the recipient serum in highly significant quantities. In some instances the titer of the new Gm remained con-stant whereas in others there was a very gradual diminution but never a complete loss of the added Gm type. Special Pathologic Studies: The sex iQ-entification was performed in nine homografts :y2, :y2, 4, 11, 23, 35, 105, 380, and 400 days after transplantation. At all times the vascular endothelial cells remained male. However, the Kupffer cells became female and therefore of host origin in the three livers with the longest host residence. In each of the 12 hepatic homografts in which a special search was made for lymphoid tissues, these were found. The lymphoid follicles had prominent germinal centers and many plasma cells in the medulla. CONCLUSIONS These observations indicate that new IgG phenotypes may be in-troduced by hepatic homotransplantation and maintained for long periods thereafter. The new immunoglobulins are apparently not from cell lines differentiating from Kupffer cells since the latter cells eventually become the genotype of the host. It is probable that lymph-oid tissue transplanted with the liver is the source of the donor type IgG found in some of the patients long after transplantation. REFERENCES 1. STARZL, T.E., MARCHIORO, T.L., ROWLANDS, B.T., JR., KIRKPATRICK, C.H., WIL-SON, W.E.C., RUSKIND, D. and WADDELL, W.R. Immunosuppression after experi-mental and clinical homotransplantation of the liver. Ann. Surg., 1964, 16:411-39. 2. KASHIWAGI, N., GROTH, C.G. and STARZL, T.E. Changes in serum haptoglobin and group specific component after orthotopic liver transplantation in humans. Proc. Soc. Exp. BioI. Med., 1968, 128:247. 3. ALPER, C.A., JOHNSON, A.M., BIRTCH, A.G. and MOORE, F.D. Human C'3: Evi· dence for the liver as the primary site of synthesis. Science, 1969, 163:286. 4. MARTENSSON, L. On the relationship between the gamma.globulin genes of the Gm system. J. Exp. Med., 1964, 120:1169. 5. KASHIWAGI, N. Special immunochcmical studies. In Experience in Hepatic Transplantation edited by T.E. Starzl, Philadelphia: W.B. Saunders Co., 1969. 6. BARR, M.L., BERTRAM, L.F. and LINDSAY, H.A. The morphology of the nerve cell nucleus, a¢cording to sex. Anat. Rec., 1950, 107:283. 7. PORTER, R.A. Pathology of the orthotopic homograft. In Experience in Hepatic Transpymtation edited by T.E. Starzl, Philadelphia: W.B. Saunders Co., 1969. 

Studies of homograft sex and of gamma globulin phenotypes after orthotopic homotransplantation of the human liver.

Name not available

Studies of homograft sex and of gamma globulin phenotypes after orthotopic homotransplantation of the human liver

http://d-scholarship.pitt.edu/3586/1/31735062124114.pdf

Studies of homograft sex and of gamma globulin phenotypes after orthotopic homotransplantation of the human liver.

Abstract

Similar works

Full text

Available Versions

D-Scholarship@Pitt

Name not available

Name not available