PubMed Health⌕ Search

Biomedical subjects

A Wadgymar

Publications and source records attributed to A Wadgymar.

12 recordsLinked to original sources
PubMed1990

The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I-mediated rejection.

In renal transplantation, preformed cytotoxic antibody against donor HLA class I antigens causes hyperacute rejection of renal allografts, but its pathogenic significance when it develops in the posttransplant period is unknown. In the present studies we describe the clinical and pathologic features of patients with rejection associated with anti-class I. In the course of 400 consecutive cadaveric renal transplants, 7 patients were identified who had antibody against donor class I HLA antigens in association with atypical but distinctive patterns of rejection. All 7 were presensitized. In 3 patients, the transplant had been inadvertently performed with a positive donor-specific T cell crossmatch. In the remaining 4, the T cell crossmatch on current sera was negative but became positive posttransplant. The clinical picture was deterioration of graft function with rapid onset of oliguria, apparently due to acute tubular necrosis, but with persistence of blood flow demonstrable by radioisotope scan studies. Renal histology showed that the typical lesions observed in cell-mediated rejection, such as tubulitis and interstitial infiltration, were absent. Granular complement deposition (6), polymorphonuclear infiltration (6), and endothelial injury in the microvasculature (6) were common, and mononuclear infiltrates were absent (2) or not prominent (4). In 3 patients the glomerular changes resembled a picture of hemolytic uremic syndrome, with capillary fibrin thrombi and widening of the subendothelial space. IgG staining was negative. The pathologic features suggest that anti-class I antibody appearing or persisting in the early posttransplant period injures the endothelium of the microvasculature, with the clinical presentation different from that of hyperacute rejection. Particularly in sensitized patients, rapid deterioration in function, leading to a picture of acute tubular necrosis, with pathologic features of endothelial injury in the microcirculation, should suggest the diagnosis of anti-class I-mediated rejection.

Adult↗
PubMed1987

Crossreactions between an I-A allospecificity and the cytoskeleton of glomerular epithelium and of vascular smooth muscle.

During studies to investigate the localization of Ia antigens in normal mouse kidney, a monoclonal antibody (Mab) specific for I-Ab by microcytotoxicity criteria was found to crossreact with a tissue antigen present in the glomeruli and vasculature of murine tissues, irrespective of their Ia haplotype, as well as in human kidneys. Immunofluorescence and immunoperoxidase studies of frozen tissue sections revealed that the antigen responsible for the crossreaction was present in the cytoplasm of glomerular epithelial cells and of smooth muscle of blood vessels. The immunofluorescence pattern of primary cultures of human glomerular epithelial cells and of a glioblastoma cell line indicated that the crossreactive antigen forms part of the cytoskeleton, and resembled the pattern observed with a monoclonal against vimentin, one of the intermediate filaments. Thus this Mab, which is directed against mouse alloantigen Ia.20 in microcytotoxicity was found to crossreact with a cytoskeletal component present in the mouse, as well as in human glomerular epithelial and smooth muscle cells.

Animals↗
PubMed1984

Graft-vs-host reactions induce H-2 class II gene transcription in host kidney cells.

To study the effect of immunologic stimuli on renal expression of Ia antigens (the class II products of the major histocompatibility complex), we induced acute graft-vs-host disease (GVHD) in mice and assessed Ia expression in the host kidney. Serologic absorption analyses showed that the amount of host Ia antigen increased up to tenfold in kidney, and immunofluorescence demonstrated that this increase occurred predominantly in renal tubule epithelial cells. To determine whether these alterations reflected changes in Ia gene transcription, we hybridized DNA probes for mRNAs encoding either Ia E alpha or A beta chains to total RNA extracted from the kidneys of normal mice and mice with acute GVHD. Northern hybridization blots revealed that the level of Ia mRNA expression in GVHD kidney is enhanced about sevenfold when compared with that found in normal kidney. Using the E alpha probe, this result was shown to reflect increased expression of C3H host Ek alpha mRNA, since the Eb alpha gene is not transcribed by the C57BL/6 donor strain used. We conclude that the increase in expression of Ia in renal tubule epithelium during GVHD probably reflects increased I-region gene transcription in host kidney cells. These findings may have implications for the pathogenesis of renal allograft rejection and immunologic renal disease.

Animals↗
PubMed1984

Changes in Ia expression in mouse kidney during acute graft-vs-host disease.

We induced graft-vs-host disease (GVHD) in mice to determine whether immunologic stimuli could alter renal Ia expression. Two strain combinations were used: B6.C-H-2bm12 into C57BL/6, an I-A mutation difference, and A.SW into A.TL, differing in the I and D regions of H-2. By day 10 after allogeneic reconstitution of lethally irradiated recipients with bone marrow and spleen cells, the recipients had developed acute GVHD, as measured by their spleen to body weight ratio. Histologic examination revealed focal interstitial infiltrates of mononuclear cells in the kidneys. The expression of host Ia in these kidneys was increased up to 10-fold, as measured by absorption, and indirect immunofluorescence indicated that certain renal tubule cells had become strongly positive, suggesting that these were the principal sites of the increase in Ia expression. Similar increases were not observed in donor Ia. Tubule cells may have become Ia positive by passive uptake, or more probably, by the increase of Ia biosynthesis in cells that usually synthesize little or no Ia. Lethal irradiation without reconstitution tended to decrease renal Ia expression, as assessed by absorption and immunofluorescence. The results indicate that renal Ia expression, particularly in renal tubules, can be altered by changes in the immune system, raising the possibility of a role for such altered Ia expression in autoimmune or alloimmune responses involving the kidney.

Absorption↗