Immunofluorescent Examination of Biopsies from Long-Term Renal Allografts

Abstract

Immunofluorescent examination of open renal biopsies revealed clear-cut glomerular localization of immunoglobulins not related clearly to the quality of donor-recipient histocompatibility in 19 of 34 renal allografts. The biopsies were obtained 18 to 31 months after transplantations primarily from related donors with a variable quality of histocompatibility match. IgG was the predominant immunoglobulin class fixed in 13 biopsies, and IgM in six. The pattern of immunoglobulin deposition was linear, connoting anti-GBM antibody in four of the 19; it was granular and discontinuous, connoting antigen-antibody-complex deposits, in 13. An immune process may affect glomeruli of renal allografts by mechanisms comparable to those that cause glomerulonephritis in native kidneys. The transplant glomerulonephritis may represent a persistence of the same disease that originally destroyed the host kidneys or the consequence of a new humoral antibody response to allograft antigens.The occurrence of glomerular lesions in viable renal allografts has been well documented by light and electron microscopy of biopsy material. [1][2][3][4] Understanding of the pathogenesis for the morphologic changes, however, is not clear. In particular, uncertainty exists concerning the role of well defined mechanisms 5,6 known to mediate glomerulonephritis in native kidneys in causing glomerular disease in the transplanted kidney.It is the purpose of this report to present results of immunofluorescent examinations of 34 human renal allografts. These observations are derived from a series of renal grafts, functional 18 to 31 months after implantation. All but three of the kidneys were from living, related donors, and all the recipients were treated initially with antilymphocyte globulin (ALG). 7 The results indicate considerable focal or generalized immunoglobulin deposits in glomeruli of over half the allograft biopsies studied, and document the occurrence of antiglomerular basement-membrane (anti-GBM) antibodies, in 20 per cent of the glomeruli showing such fixation. Although immunoglobulin M (IgM) occasionally was found in the absence of immunoglobulin G (IgG), IgM deposits were usually in the company of IgG deposits, often of a different distribution and distinctly less extensive.The data are compatible with the hypothesis that the glomerular lesions observed are the result of conventional mechanisms known to cause glomerulonephritis in native kidneys. Such a hypothesis suggests that the glomerular injury in the allografts is either a result of the same antibody responsible for the pre-existing processes that originally destroyed the patient's own kidneys or a de novo humoral-antibody response to the alien antigens of the new organ. MATERIALS AND METHODSThirty-five patients receiving renal allografts at Colorado University Medical Center between June 21, 1966, and August 25, 1967, were readmitted to the Center in January, 1969, for routine re-evaluation and biopsy of the transplants. An additional patient with cystinosis who had had a t...

Immunopathological Studies of Orthotopic Human Liver Allografts

“…Morphological and immunopathological studies of human renal [1][2][3][4][5][6][7][8][9] and cardiac 10,11 allografts have shown that circulating immunoglobulins and complement probably play an important part in the rejection of these organs. In this report we seek evidence of the same mechanism in hepatic allografts.…”

Evidence Suggesting Persistence of Nephritogenic Immunopathologic Mechanisms in Patients Receiving Renal Allografts

“…Observed patterns of Ig in allografts were linear in seven kidneys, granular in three and indeterminate in four. Three of these patients had received ATG (patients J. W., M. B., and M. C.); direct IF was negative for horse globulin fixation, as it was also in patient T. T. Survey of one series of long-functioning, living related-donor allografts by immunohistochemical analyses of surgical biopsies indicated a high frequency of immunoglobulin-associated glomerular abnormalities (23). Moreover, the report documented in that group the apparent incidence of linear and other patterns of host immunoglobulin localization, presumptive of anti-GBM, and soluble antigen antibody complex-mediated glomerulonephritis.…”

Urine Plasmin-Like Substances as an Index of Kidney Allograft Rejections

“…A number of other tests for rejection have been devised which generally depend on looking at the products of secondary damage to the graft, including lysozymuria (8), elevation of blood and urinary histamine (18), and increased urinary FDP (1)(2)(3)5,9,21,25). Renal biopsies have been studied for this purpose (17), but there is no morphological finding that is completely specific for rejection.…”