Alan G. Birtch

Human renal allografts: Glomerular deposits of horse immunoglobulin G and nephritis following administration of antilymphocyte globulin

Abstract The administration of horse antilymphocyte globulin (ALG) containing glomerular basement membrane (GBM) cross-reactive antibody has the potential for inducing nephritis of the anti-GBM (linear) type. Similarly, a hostantihorse antibody response to the ALG may result in antigen-antibody complex (granular) nephritis. GBM cross-reactive antibody is more likely to be present in ALG derived from horses immunized with suspensions of lymph modes or thymus than with washed lymphoid cell suspensions, possibly because of the presence of other tissue antigens. However, ALG derived from some of our horses immunized with washed human thoracic duct lymphocytes also contained antibody cross-reactive with human GBM. Such antibody was found to be intermittently present in subsequent bleeds (ALG lots) following its demonstration in initial or early ALG lots. An ALG lot submitted for our evaluation of its possible GBM cross-reactivity was strongly positive but showed a marked reduction in cross-reactivity during extended storage at −20°C. Therefore, each lot of ALG should be tested for the presence of GBM cross-reactive antibody immediately after preparation. Of 58 renal allograft recipients treated intramuscularly with ALG and other immunosuppressants, allograft biopsies were taken for specific indications in 32. Examination of these biopsies for deposits of horse immunoglobulin G (IgG) showed that two contained linear deposits, suggesting that the cross-reactive antibody had not been completely absorbed locally following intramuscular administration. One of the latter two immunosuppressed recipients developed nephritis, probably a result of GBM cross-reactive antibody, from which he subsequently recovered. Although not all patients who received ALG containing GBM cross-reactive antibody develop clinically significant nephritis, until more data are available regarding the nephrotoxic effects of ALG, only lots found not to contain such antibody should be used clinically.

Factors responsible for urinary fistula in the renal transplant recipient.

T HE DEVELOPMENT of a urinary htula after renal transplantation remains a dangerous and often lethal complication. As a result of reviewing the Peter Bent Brigham Hospital experience with renal transplantation over the past 20 years, the following clinical impressions have evolved: 1 ) The incidence of urinary fistula in the patient with more than one donor renal artery has been consistently greater than its single artery counterpart. 2) Those patients who have undergone a recent allograft rejection might develop a urinary fistula when function resumed. 3) The difficulty with which the donor kidney was harvested might be of some importance regarding the development of urinary fistulae. This study was undertaken to test these impressions and to identify those factors which might be prognostic in selecting transplant recipients at greater risk for urinary fistula development.

Histocompatibility (HL-A) antigens and cancer of the breast: Association with antigen HL-A7☆

Abstract One hundred twenty-three control subjects and fifty-two caucasian female patients with cancer of the breast were typed for thirteen HL-A antigens. The frequency of the antigen HL-A7 and of haplotypes bearing this antigen were significantly higher in the group with cancer. HL-A7 positivity may be associated with increased susceptibility to cancer of the breast.

THE MONKEY SKIN GRAFT MODEL AS AN ASSAY OF HUMAN ANTILYMPHOCYTE GLOBULIN

SUMMARY Thirteen lots of horse antihuman lymphocyte globulin (ALG), produced using several different antigen sources and methods of preparation, were tested in the primate skin allograft assay system. Each ALG tested showed significant prolongation of skin allograft survival (range, 15-44+ days; average, 22.79 ± 8.93 days) compared to the control (9.95 ± 1.46 days). No antigen source, method of preparation, or route of administration produced consistently longer survival and none prevented the formation of specific antibody against the skin graft donors. I.v. administered ALG did not lead to the fixation of antiglomerular basement membrane (GBM) antibody as assessed by conventional immunofluorescent techniques and resulted in a lower incidence of antihorse IgG antibody production than that following administration by the s.c. route. One lot of ALG, however, caused fatal disseminated intravascular coagulation in four monkeys, only when administered i.v. A positive correlation between primate skin allograft survival and rosette inhibition (RI) titers was not demonstrated.

Organ transplantation in New England. An anniversary note.

IN a recent Journal report, the Massachusetts Department of Public Health described some aspects of kidney transplantation in Massachusetts.1 As we pass the 20th anniversary of the first human-kidn...

Renal allografting in the patient with juvenile diabetes mellitus

Abstract A case is presented to illustrate the change in our thinking regarding allotransplantation in patients with terminal juvenile diabetic nephropathy. The absence of any histopathologic changes in the first renal allograft after 704 days of transplantation encouraged us to proceed and transplant a second renal allograft from the patients mother. The second graft has functioned well to date.

Hyperimmune F(ab′)2 antibody: Role in canine hyperacute renal allograft rejection☆

An attempt to obtain protection of the renal allograft in a sensitized recipient by ex vivo perfusion with F(ab′)2-modified antibody was unsuccessful. The major contributing factor to this failure appeared to be related to the species differences in IgG and their mode of degradation. The canine IgG molecule proved to be very hard to degrade to F (ab′)2 as tested by the loss of the lymphocytotoxic titer at the end of 20 hr of pepsin digestion.