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A B Collins

Publications and source records attributed to A B Collins.

34 records · Page 2Linked to original sources
PubMed1985

Characterization of antigens and antibody specificities involved in Heymann nephritis.

The present study was conducted to determine if Fx1A, a renal cortical extract used to induce Heymann nephritis, contains nephritogenic antigens in addition to the brush border-derived glycoprotein gp 330. Of 26 Lewis rats immunized with Fx1A, 24 developed abnormal proteinuria (greater than 20 mg/24 hr) by wk 10, whereas of 15 rats immunized with a partially purified gp 330 preparation (MVH), only one developed proteinuria. Immunofluorescence studies showed that all Fx1A rats developed large, diffuse, granular deposits along the glomerular basement membrane which stained brightly for IgG and C3; only 11 of the 15 MVH rats had definite deposits; in most rats, they were small and stained only moderately for IgG and faintly or not at all for C3. The Fx1A and MVH rats developed comparable levels of antibodies to MVH (gp 330) before the onset of proteinuria in Fx1A rats, after which serum IgG and antibody levels declined. In contrast, antibodies against soluble Fx1A antigens appeared earlier and rose more rapidly in Fx1A than in MVH rats. Larger amounts of IgG could be eluted from the glomeruli of Fx1A rats than from MVH rats. Eluates from the Fx1A rats contained antibodies that reacted with gp 330 and also a 95 kd antigen; the latter reactivity was not demonstrated in eluates of MVH rats. Immunoprecipitation studies showed that both gp 330 and the 95 kd antigen are components of normal glomeruli. The results show that immunization with Fx1A produces a more severe form of Heymann nephritis than does gp 330, and that Fx1A contains at least one nephritogenic antigen in addition to gp 330.

Animals↗
PubMed1985

Immunopathologic studies of adult linear IgA bullous dermatosis.

Three cases of adult linear IgA bullous dermatosis were examined to determine the types of IgA present in the basement membrane zone. IgA 1 subclass, without IgA2, was identified in all three cases; J chain was identified in only one case. Secretory component was absent in all cases. Two observations can be made from this study. First, the predominance of monomeric IgA1 is more compatible with the pattern of antibody secretion of plasma cells present in extragut sites than in intestinal sites. These findings are further evidence of the distinction between dermatitis herpetiformis, which has polymeric IgA1, and adult linear IgA bullous dermatosis and may suggest an extragut site for the origin of the antibodies. The second observation is that the antibodies in adult linear IgA bullous dermatosis show limited expression of heavy and light chains and molecular size that cannot be explained by origin in any compartment. The origin of this limitation cannot be determined from the present data, but possible explanations include a monoclonal or oligoclonal origin of the plasma cells secreting the anti-basement membrane antibodies, genetic restriction of either the immunoglobulin repertoire or helper T-cell response such that only an IgA subpopulation is permitted to be produced in response to the antigen, and selective absorption from the sera or deposition in the skin.

Adult↗
PubMed1985

Studies with monoclonal antibodies against brush border antigens in Heymann nephritis.

The authors have prepared and studied three murine monoclonal antibodies that are reactive with antigens in brush border regions of proximal renal tubules of rats. Two of the antibodies, 14C1 and AG3, were derived from mice immunized with Fx1A and the third, 4H6, from a mouse immunized with isolated glomeruli obtained from rats with Heymann nephritis. Immunohistochemical, immunoelectron microscopic, and immunochemical studies showed that the three antibodies recognized different antigens. The antibody 14C1 recognized the previously described nephritogenic glycoprotein, gp 330, in microvillar brush border preparations, and reacted with material present on podocyte cell surfaces of normal rat kidneys, especially in coated pits, as well as with material in the glomerular deposits of rats with Heymann nephritis. The antibody 4H6 recognized a 110-kilodalton microvillar antigen and reacted with material in the glycocalyx of podocytes of normal glomeruli, but showed only equivocal reactivity with material in the deposits in Heymann nephritis. AG3 failed to immunoprecipitate a distinctive antigen in microvillar preparations and did not react with the glomeruli of normal rats or of rats with Heymann nephritis. All three antibodies reacted with epithelial cells in the intestine, epididymis, and placenta; 4H6 also reacted with thin loops of Henle as well as with endothelial cells or other cells in lung, lymphoid tissue, liver, and spleen. The results demonstrate that not all brush border antigens participate in Heymann nephritis and confirm that an antigen (gp 330) involved in the formation of glomerular deposits in Heymann nephritis is normally present on podocyte surfaces, especially in coated pits, but is not present in extracellular sites.

Animals↗
PubMed1984

Systemic cell-mediated reactions in vivo. Effect of the interaction of circulating antigen with sensitized lymphocytes on glomeruli and pulmonary alveoli.

The effects of systemic cell-mediated hypersensitivity reactions on glomeruli and lungs were investigated in rats. The animals were given an intravenous injection of antigen 7 days after sensitization or were given an intravenous injection of lymph node cells from sensitized syngeneic donors 1 day after antigen injection. Control animals were given an irrelevant antigen or saline. All animals received three injections of 3H-thymidine during the course of the experiments. The animals were sacrificed 2 or 3 days after antigen injection. Autoradiographs of renal and pulmonary tissue showed significantly more labeled mononuclear cells in glomeruli and pulmonary alveolar walls in the experimental groups than in the control groups. Immunofluorescence studies did not reveal antigen, rat IgG, or C3 in glomeruli. The results indicate that systemic cell-mediated reactions can lead to an accumulation of mononuclear cells in glomeruli and lungs, an effect that may contribute to tissue injury.

Animals↗
PubMed1983

Hepatitis B immune complex glomerulonephritis: simultaneous glomerular deposition of hepatitis B surface and e antigens.

A case of a 29-year-old homosexual male with chronic hepatitis B infection, cryoglobulinemia, and glomerulonephritis is described. The glomerular lesions were not readily classified, but exhibited features consistent with immune complex deposits, in both peripheral loop (predominantly epimembranous) and mesangial sites. Immunofluorescence studies, which included the use of a monoclonal antibody, showed that HBsAg was present in mesangial deposits but not in peripheral loop deposits. Immunoperoxidase studies employing HRP-conjugated anti-HBc and anti-HBe provided evidence that the epimembranous deposits contained HBe. Studies of the patient's serum revealed high titers of HBsAg, low titers of HBeAg, as well as anti-HBe and anti-HBc. The cryoglobulins contained small amounts of HBsAg, HBeAg, and anti-HBc, but anti-HBe and anti-HBs antibodies were not found. The possible mechanisms accounting for accumulation of HBsAg and HBeAg in glomeruli are discussed. In addition, the literature concerning the nature of hepatitis B antigens found in glomerular deposits is reviewed.

Adult↗
PubMed1981

Glomerulopathy associated with cytomegalovirus viremia in renal allografts.

We investigated the relation between cytomegalovirus (CMV) infection and renal-allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression, and CMV-associated glomerulopathy occurring seven weeks after transplantation and responding to decreased immunosuppression. We conclude that viremic CMV infection can cause acute glomerular injury and that recovery may be favored by a decreased in immunosuppressants.

Cytomegalovirus Infections↗
PubMed1981

Lack of evidence for a role of renal tubular antigen in human membranous glomerulonephritis.

Renal tissue from 71 patients with membranous glomerulonephritis was studied for the presence of renal tubular antigens in glomerular deposits by indirect immunofluorescence, using a rabbit antiserum prepared against a human renal tubular antigen, Fx1A. The rabbit antiserum was reactive with antigens normally present in the brush border regions of proximal tubules of human and rat kidneys and in the glomerular deposits of rats with Heymann nephritis. However, renal tubular antigens were not detectable in any of the cases of human membranous glomerulonephritis, either before or after partial elution of immunoglobulins from glomeruli. Eluates of renal tissue from 5 of the patients and sera from 6 patients did not contain antibodies against renal tubular antigens demonstrable by immunofluorescence. These findings fail to provide evidence for a role of renal tubular antigens in human membranous glomerulonephritis.

Adolescent↗
PubMed1981

Effect of circulating immune complexes on Fc and C3 receptors of Kupffer cells in vivo.

Lewis rats were given a single intravenous injection of soluble immune complexes, composed of human serum albumin and rabbit anti-human serum albumin, prepared with either whole antiserum or purified IgG antibodies. The animals were sacrificed at intervals ranging from 2 to 24 hours, and Fc and C3 receptor activities of Kupffer cells were studied in Kupffer cell-enriched suspensions and in frozen sections of liver, using red cell rosetting techniques employing IgGEA and IgMEAC reagents. At 2 to 12 hours, there was reduction or loss of Fc and C3 receptor activity. The extent of reduction correlated with the amount of complexes injected. Both C3 and Fc receptor activity returned to normal levels within 24 hours. Immunofluorescence revealed rabbit IgG in numerous Kupffer cells at 2 hours, but in almost none at 6 to 12 hours after injection. 125I trace-labeled immune complexes were shown to be cleared more slowly than normal in animals injected 2 hours earlier with immune complexes. The findings show that circulating immune complexes can produce loss of Fc and C3 receptor function of Kupffer cells in vivo and provide evidence that this can result in diminished clearance of complexes.

Animals↗
PubMed1979

A cell-mediated reaction against glomerular-bound immune complexes.

Lewis rats were given a single i.v. injection of soluble immune complexes containing human serum albumin (HSA) and rabbit anti-HSA antibodies, prepared in antigen excess. This resulted in localization of HSA and rabbit gamma globulin (RGG) in glomerular mesangial regions without producing definite histologic changes. 24 h after the injection of immune complexes, groups of these rats received lymph node cells or T-cell preparations from syngeneic donors sensitized to RGG, HSA, or ovalbumin; another group received no cells. All of these groups and a group of normal control rats were given injections of [3H]thymidine at 18, 27, and 44 h. The animals were killed 48 h after the time of cell transfer. In histologic sections, glomerular abnormalities were found only in some of the animals that had received immune complexes and lymph node cells or T-cell populations from donors sensitized to HSA or RGG; the lesions were characterized by focal and segmental increase in cells in mesangial regions. Autoradiographs revealed significantly greater numbers of labeled cells in mesangial regions and glomerular capillaries in the groups that had received immune complexes and cells from HSA- or RGG-sensitized donors than in any of the other groups. Electronmicroscopic studies suggested that the increase in cellularity in mesangial regions resulted from an influx of mononuclear phagocytes. The findings indicate that cell-mediated reactions can be initiated by the interaction between sensitized T lymphocytes and antigens present in immune complexes within mesangial regions.

Animals↗
PubMed1978

Evidence for a pathogenic role of a cell-mediated immune mechanism in experimental glomerulonephritis.

Lewis rats were injected intravenously with rabbit anti-rat glomerular basement membrane (GBM) antisera in doses that were sufficient to cause glomerular fixation of rabbit gamma globulin (RGG) detectable by immunofluorescence, but which failed to induce histologically detectable lesions. 24 h later, groups of rats received lymph node cells or serum from syngeneic donors that had been immunized with either RGG or ovalbumin; they were injected with [3H]thymidine three times during the next 2 days, and sacrificed 48 or 96 h after transfer. Only the rats given anti-GBM antiserum plus lymph node cells from donors sensitized to RGG showed histological glomerular lesions, in the form of segmental hypercellularly and necrosis. Autoradiographs revealed the greatest number of labeled cells in glomeruli in the same group. In analogous experiments, it was shown that T-cell-enriched populations could induce hypercellular glomerular reactions. On the basis of electronmicroscopic and autoradiographic observations, it appears that the glomerular hypercellularity resulted from both infiltration of mononuclear cells and proliferation of endothelial cells. The findings indicate that interaction of specifically sensitized lymphocytes with glomerular-bound antigen can induce a cell-mediated (delayed-type) reaction in glomeruli.

Animals↗
PubMed1978

Glomerular C3 receptors in human renal disease.

The relationship between glomerular C3 receptor activity and intraglomerular C3 deposition was studied in 73 cases of various forms of renal disease. C3 receptor activity was measured by enumeration of complement-coated sheep red blood cells (IgM EAC) that adhered to glomeruli in frozen sections and expressed as a percentage of the mean number present in control kidneys. Adjacent sections were studied for the presence and distribution of C3 deposits. The precise location of corresponding dense deposits was determined through 1-mu sections or electron micrographs. Marked depression of C3 receptor activity was found in most cases in which there was accumulation of C3 along the glomerular basement membrane, irrespective of whether the deposits were in a subepithelial, intramembranous, or subendothelial location. In contrast, when C3 was not detectable or was found exclusively in the mesangium, C3 receptor activity was affected only moderately, if at all. These data are consistent with the hypothesis that the interaction of C3 with podocytes is a major determinant in the loss of C3 receptor activity in glomerular disease, but do not exclude the possibility that interaction with mesangial or endothelial cells may also influence C3 receptor activity.

Adenocarcinoma↗
PubMed1976

Studies on the pathogenesis of experimental anti-tubular basement membrane nephritis in the guinea pig.

Using the model of renal disease induced in guinea pigs by immunization with bovine TBM preparations in adjuvant, the following observations were made. Animals with activity induced disease show bright staining for IgG along the TBM and only faint, inconstant staining along the GBM. Following transfer of serum animals with anti-TBM disease to normal recipients, accumulation of IgG was found predominantly in glomeruli at 4 hours, but at Days 3 and 5, IgG was seen predominantly along the TBM. There was no appreciable accumulation of neutrophils in the kidneys of recipients of anti-TBM serum, even at early intervals (4 and 24 hours) after transfer. However, within 2 days, small numbers of mononuclear cells were found. By Day 3, mononuclear cells were numerous, and multinucleate giant cells and tubular cell damage were present. After that, the lesions increased in severity and by 10 days were indistinguishable from those found in actively immunized animals at 14 to 21 days. Study of frozen section of kidneys obtained from animals with active disease at 14 days, employing sheep cells coated with rabbit antibody (IgG EA) revealed rosettes around many of the mononuclear cells in the infiltrate, indicating that they are mononuclear phagocytes (monocytes or macrophages). IgM complexed with sheep cells and complement (EAC) did not react and thus failed to provide evidence for the presence of B lymphocytes. Transfer of 7 X 10(8) lymph node cells from the TBM-immunized Strain 13 donors to normal Strain 13 recipients failed to result in renal lesions. The findings are interpreted as indicating that anti-TBM antibodies mediate the renal disease without the participation of cell-mediated immunity and further that these antibodies bring about an influx of ciculating mononuclear cells, predominantly monocytes, without attracting appreciable numbers of neutrophils.

Animals↗