Differential expression of CD43 (leukosialin, sialophorin) by mononuclear phagocyte populations.

CD43 is a hematopoietic cell antigen whose distribution includes T lymphocytes, plasma cells, neutrophils, and platelets. Although it has been detected on peripheral blood monocytes, its expression by other mononuclear phagocytes has not been well documented. Possible changes in monocyte/macrophage CD43 expression in response to inflammation are also poorly defined. To examine these questions, the expression of CD43 by rat peripheral blood monocytes and both resident and elicited peritoneal macrophages was examined. By flow cytometry with two anti-CD43 monoclonal antibodies, blood monocytes were found to express large amounts of surface CD43, whereas surface CD43 expression by resident peritoneal macrophages was negligible. Peritoneal macrophage populations elicited by intraperitoneal injection of thioglycollate were uniformly positive for surface CD43, although the level of expression was lower than that found on monocytes. By labeling resident macrophages with a fluorescent tracer dye, this phenotypic shift was found to reflect an influx of CD43-positive elicited macrophages coupled with a disappearance of CD43-negative resident cells. Evidence from both flow cytometry and Western blotting studies suggests that the CD43 expressed by elicited peritoneal macrophages is less heavily sialylated than that expressed by blood monocytes. These findings, coupled with recent evidence that CD43 influences cellular adhesion, indicate that differential expression of CD43 may play a role in monocyte/macrophage trafficking.

Alterations in renal interleukin-1 production during kidney transplant rejection in the rat. The effects of high-dose methylprednisolone.

To characterize the role of interleukin-1 in renal allograft rejection, we examined the temporal relationship of IL-1 production to changes in renal function and histology in a rat kidney transplantation model. In rat renal allografts, both glomerular filtration rate and renal plasma flow (RPF) fell progressively from days 4 through 6 following transplantation. The reduction in allograft function was accompanied by histologic changes consistent with rejection and enhanced steady-state levels of IL-1 beta mRNA measured by Northern blot. This increase in IL-1 beta mRNA levels was associated with a forty-fold increase in IL-1 bioactivity in eluates of kidney allografts compared with isografts. In rejecting allografts, these changes also coincided with increased production of thromboxane B2 (TxB2) by the graft. To attempt to modify IL-1 production in the transplanted kidney, a separate group of animals with renal allografts were treated with 80 mg/kg/day of methylprednisolone for 6 days. GFR in MP-treated animals was significantly preserved compared with vehicle-treated animals. However, similar histologic manifestations of rejection were found in both groups. Although IL-1 beta mRNA levels in the kidney were not changed with MP treatment, renal IL-1 bioactivity was reduced four-fold in animals that received MP compared with controls. Thus, IL-1 beta gene expression and IL-1 protein production are stimulated in rejecting kidney transplants. MP administration improves allograft function and inhibits IL-1 production, apparently at a post-transcriptional level. We hypothesize that overproduction of IL-1 during kidney transplant rejection may promote allograft dysfunction and injury. Some of the beneficial effects of corticosteroids in acute rejection may be mediated through inhibition of IL-1 release within the allograft.

Transplantation for polycystic kidney disease.

During the 4-year period from June 1977 to May 1981, a total of 108 patients with polycystic kidney disease and 2440 nonpolycystic patients received cadaver renal allografts in the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study. There were no significant differences between the groups with and without polycystic disease in terms of recipient blood group, history of splenectomy, or preformed antibody status. As a group, transplanted polycystic patients underwent native nephrectomy more often, had a better HLA match, received less antilymphocyte serum (ALS), and were slightly older than nonpolycystic patients. Although proportionately fewer polycystic patients received pretransplant transfusions than nonpolycystic patients (P = .002), transfusion was associated with a significant increase in graft survival in the polycystic group (P less than .05), as well as in the nonpolycystic group (P less than .0001). Gene frequency analysis showed no HLA-A, or -B antigen linkage with polycystic disease. No significant differences existed between the polycystic and nonpolycystic groups in terms of overall graft and patient survival. However, transplanted polycystic patients died more frequently from bacterial sepsis (P less than .05), especially from gram-positive organisms (P = .01). Pretransplant bilateral nephrectomy did not affect the incidence of sepsis. However, following graft failure, patients with bilateral native nephrectomy had a greater incidence of severe anemia (50% versus 39%) and death (58% versus 25%; P less than .05) than those with unilateral nephrectomy or no nephrectomy. Treatment with ALS did not significantly improve graft survival in those with polycystic disease. A strong positive correlation was found between patient death and treatment with ALS only in the polycystic group (P less than .01). These findings indicate that the use of pretransplant bilateral native nephrectomy and posttransplant ALS should be judicious in the polycystic patient because they may be associated with increased morbidity and mortality.

Characterization of human anti-porcine "natural antibodies" recovered from ex vivo perfused hearts--predominance of IgM and IgG2.

Hyperacute rejection is a major obstacle to successful transplantation of vascularized xenogeneic organs and is believed to be mediated at least in part by performed xenoreactive "natural antibodies" (NAb). In this study, human NAb that could be involved in hyperacute rejection of pig heart xenografts were identified and characterized using an ex vivo model in which pig hearts were perfused with whole blood from individual human or pig donors. This ex vivo perfusion model allows for the continuous monitoring of physiologic parameters of cardiac function as well as sequential sampling of tissue and blood. Pig hearts perfused with allogeneic pig blood maintained normal function for at least 4 hr, whereas those perfused with xenogeneic AB+ human blood never achieved normal function and rejected completely after 30 min. In three separate experiments involving different human blood donors and pig hearts, sequential samples of perfused blood revealed a progressive depletion of anti-porcine NAb. Samples of all three rejected cardiac xenografts were homogenized, and the specifically bound human anti-porcine antibodies were eluted with citric acid. The eluted antibodies were enriched approximately 50-120-fold for anti-porcine reactivity compared with serum from the corresponding donor. Eluates contained NAb of predominantly IgM and IgG2 isotypes. Immunofluorescence histology confirmed the deposition of IgM and IgG2 but not other IgG subclasses in the rejected pig hearts. Since IgG2 utilized predominantly in response to bacterial polysaccharide antigens, our findings are consistent with the possibility that some NAb arise via crossreactivity with microbial antigens and are predominantly directed against carbohydrate rather than protein antigens.

Rejection of kidney allografts by MHC class I-deficient mice.

To evaluate the requirement for CD8+ T cells in kidney transplant rejection, we studied class I-deficient (class I-) mice that had received vascularized renal allografts. Because of the absence of MHC class I expression, these mice are grossly deficient in CD4-CD8+ alpha beta TCR+ cells. Despite the deficiency of CD8+ T cells in naive class I- mice, kidney allografts transplanted into class I- recipients developed significant reductions in renal blood flow and glomerular filtration rate to levels comparable to allograft controls. This functional deterioration was associated with histologic changes consistent with cellular rejection. There were no significant differences in the pattern, severity, or phenotypic character of the cellular infiltrate in allografts transplanted into class I- recipients compared to controls. In fact, substantial numbers of CD8+ T cells were present in these allografts, and the intensity and pattern of anti-CD8 staining was not different from controls. Virtually all of the CD8+ cells in the kidney grafts were class I- and CD4- and co-expressed CD8 alpha and beta chains; the majority were alpha beta TCR+. The CD8+ infiltrating cells were cytotoxic to donor targets but also exhibited activity against class I+ cells bearing self-MHC. Despite the marked CD8+ T cell infiltration of grafts, CD8+ T cells could not be detected by flow cytometry in freshly isolated splenocytes from the class I- recipients of allografts. High levels of circulating anti-class I antibodies were present in the serum of class I- recipients of kidney allografts, and these antibodies had unusual specificity in that they appeared to recognize framework epitopes of MHC class I. Thus, class I- mice readily reject kidney allografts. Although the number of CD8+ alloreactive precursors is substantially reduced in class mice, and their specificities are atypical, the pattern and character of the intra-graft CD8+ cellular response is not significantly altered. Thus, factors unrelated to precursor frequency determine the dimension of the intra-graft CD8+ response. Such factors might include cellular and/or biochemical properties of microenvironment within the graft.

Immunosuppressive therapy as a determinant of transplantation outcomes.

Although surgical proficiency is essential to the immediate outcome of transplantation, long-term success depends upon how adequately the transplantation recipient is managed. Immunosuppression, the most critical aspect of after care, is subject to wide variation. In January 1990, a survey was sent to the directors of all transplant programs in the United States performing one or more kidney, heart, liver, heart-lung, or pancreas transplant in 1988. Detailed data were obtained on both the drugs and methods used for induction and maintenance immunosuppression, as well as the treatment of rejection. Each program director was asked to rank each immunosuppressive approach according to its perceived impact on patient outcomes. Over 85% of all eligible program directors completed the survey. There is no evidence of survey respondent bias. The use of polyclonal and monoclonal agents for induction immunosuppression was favored most by pancreas program directors (72-76%). These agents were least preferred by liver transplant programs (35-37%). About half of kidney, heart, and heart-lung program directors preferred these agents. Triple-drug therapy consisting of CsA, PRED, and AZA was considered the most preferable maintenance protocol for all transplants (i.e., kidney, 89%; heart, 94%; liver, 88%; heart-lung, 86%; pancreas, 96%). Either i.v. steroids or OKT3 were regarded as the preferred approaches for the treatment of acute or resistant rejection. Finally, the acceptability of outpatient treatment of rejection varied by transplant type (i.e., kidney, 9%; heart, 58%; liver, 5%; heart-lung, 29%; pancreas, 8%). Although there are similarities in the ratings of various aspects of immunosuppressive therapy, there are important differences. This information is critical to anticipate the implications of new immunosuppressive agents and to evaluate changes in the use of existing drugs and therapeutic approaches.

Characteristics of corneal xenograft rejection in a discordant species combination.

PURPOSE: To characterize the fate of Lewis rat corneas transplanted to Hartley guinea pigs. METHODS: Full-thickness Lewis rat corneal buttons were grafted orthotopically to Hartley guinea pigs (xenografts), ACI rats (allografts), or Lewis rats (isografts). Two panels of recipients were presensitized with xenogeneic skin grafts or allogeneic skin grafts. Serum samples were collected pre- and post-transplant and analyzed by flow cytometry and indirect immunofluorescence. RESULTS: Unlike vascularized xenografts that reject within 30 min, corneal xenografts had a mean survival time of 8 days. Presensitization with guinea pig skin grafts increased recipient IgM and IgG xenoantibody levels, as measured by flow cytometry on guinea pig hematopoietic cells, and significantly accelerated corneal xenograft rejection with a mean survival time of 5 days. Presensitization with allogeneic ACI skin grafts had no effect on xenoantibody levels or xenogeneic corneal graft survival. Guinea pig corneas stained by indirect immunofluorescence with normal rat serum exhibited low (1+) but significant binding of IgG and IgM, primarily on epithelium and stroma. Serum from Lewis rats that rejected a corneal xenograft had elevated IgG and IgM xenoantibodies that reacted strongly (4+) with guinea pig cornea and heart. CONCLUSIONS: In the discordant guinea pig-to-rat species combination, donor corneas express xenoantigens; rejection of corneal xenografts stimulates IgM and IgG xenoantibody production; sensitization to xenoantigens can accelerate corneal xenograft rejection; and discordant corneal xenografts, unlike vascularized organs, are not hyperacutely rejected.

Characterization of a novel family of ciliary body glycoproteins.

PURPOSE: To isolate and characterize ciliary body epithelial antigens reactive with a monoclonal antibody, 2B4.14.1. METHODS: A mouse monoclonal antibody generated against human corneal endothelium, 2B4.14.1 reacts with nonpigmented epithelium of human and guinea pig ciliary bodies. The ciliary body proteins reactive with 2B4.14.1 were identified by Western blotting and were partially purified by affinity chromatography with 2B4.14.1 coupled to a solid support matrix. Carbohydrate components of the antigenic molecules were analyzed by lectin chromatography and by digestion with the enzymes N-glycosidase F and endoglycosidase F. The cellular and subcellular distribution of the antigens was examined by immunoperoxidase staining and by immunoelectron microscopy of ultracryotome sections of ciliary body. RESULTS: 2B4.14.1 reacted with families of guinea pig and human ciliary body glycoproteins with estimated molecular weights ranging from 250 to 325 kD. In Western blots of samples reduced before electrophoresis, the high molecular weight bands were replaced by weakly reactive bands at 115 to 130 and 210 kD, indicating that the 2B4.14.1 ligands have disulfide bonds. 2B4.14.1 ligands from both guinea pig and human ciliary body were bound by immobilized lectins, including concanavalin A, Datura stramonium lectin, and Lens culinaris hemagglutinin, which recognize components of N-linked oligosaccharides. Guinea pig ciliary body antigens digested with N-glycosidase F and endoglycosidase F failed to react with 2B4.14.1 in Western blots, confirming the presence of N-linked oligosaccharide chains and indicating that they form an integral part of the 2B4.14.1-reactive antigenic site. Molecular weight shifts of glycosidase-digested antigens were consistent with the presence of two to four N-linked oligosaccharide units. In immunoperoxidase-stained sections of guinea pig and human ciliary body, 2B4.14.1 reacted primarily with nonpigmented epithelial cells. Staining of guinea pig epithelial cells was fairly uniform; staining of human epithelial cells was concentrated on the basal surface. By immunoelectron microscopy, a majority of the 2B4.14.1 antigenic reactivity was localized immediately external to the nonpigmented epithelial cell plasma membrane. CONCLUSIONS: 2B4.14.1 reacts with a novel family of high molecular weight glycoproteins associated with the nonpigmented epithelial cell surface in guinea pig and human ciliary body.

The effect of parental HLA compatibility on the expression of paternal haplotypes in offspring.

The compatibility of HLA-A,-B expression between mother and offspring was examined in 410 families serologically tissue typed within a single transplant lab from 1972 thru 1982. The study group included 410 mothers of 1719 children (range 2-13/mother), with 352 one-father and 58 multiple-father families There were seven cases of monozygous twins and seven cases each of maternal and paternal allelic recombination. The degree of haplotype matching between the oldest offspring and subsequent siblings was within the expected range of distribution. The number of maternal HLA-A,-B antigens matched or mismatched with paternal antigens of the offspring did not show a significant difference between early born or late born siblings either in one-father or multiple-father families. In addition, where the mother showed significant sensitization to paternal HLA-A,-B antigens ther was no apparent selection against the incompatible paternal HLA antigens or associated haplotypes in subsequent offspring. These data suggest that maternal HLA compatibility with the father is not a significant selective factor in determining the expression of paternal haplotypes in offspring.

Expression of a copper-containing amine oxidase by human ciliary body.

PURPOSE: To examine the molecular structure and ultrastructural distribution of a novel amine oxidase in human ciliary body. METHODS: Human ciliary bodies were solubilized with a nonionic detergent. The solubilized material was subjected to affinity chromatography with 2B4.14.1, a monoclonal antibody which recognizes a family of ciliary body glycoproteins. Proteins eluted from the affinity column were further separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Peptides produced from a 2B4.14. 1-reactive protein with an approximate molecular weight of 100 kDa were analyzed by Edman degradation. The protein thus identified was further examined by Western blotting and immunoelectron microscopy with anti-peptide antisera. RESULTS: Peptide sequences from the 100 kDa ciliary body protein were identical to the predicted protein sequence of an amine oxidase identified recently in a human placental cDNA library. The identity of the ciliary body protein was confirmed by Western blotting with rabbit antiserum generated against the predicted carboxy-terminal peptide of human placenta amine oxidase. Western blotting under nonreducing conditions and following glycosidase digestion indicated that the native enzyme is a disulfide-linked homodimer with multiple N-linked oligosaccharide side chains. By immunoelectron microscopy, the ciliary body amine oxidase was localized to the plasma membranes of inner epithelial cells. CONCLUSIONS: Human placenta amine oxidase is present on the plasma membranes of ciliary body inner epithelial cells. This finding provides a potential explanation for amine oxidase enzyme activity detected in previous studies of anterior segment tissues. Though the functional role of human placenta amine oxidase in the eye is unclear, it may contribute to the production of H2O2 in aqueous humor.

Inhibition of neutrophil adhesion and the membrane attack complex of complement synergistically prolongs cardiac xenograft survival.

BACKGROUND: Hyperacute xenograft rejection is affected by activation of the complement cascade. Split products of early complement components influence the localization, activation, and effector function of platelets, granulocytes, and lymphocytes, whereas the formation of the membrane attack complex (C5b-9) leads to direct cellular injury. In a unique strain of PVG rats deficient in the C6 component of complement, the terminal membrane attack complex is not formed. However, production of the chemotactic and vasoactive components C3a and C5a proceeds normally. Guinea pig cardiac xenografts in these C6-deficient rats have prolonged survival, and at the time of rejection the inflammatory infiltrate is composed primarily of neutrophils. NPC 15669, a member of a class of antiinflammatory agents called leumedins, is known to inhibit neutrophil adhesion. The purpose of this study was to determine whether inhibition of neutrophil recruitment in animals incapable of membrane attack complex formation would prolong cardiac xenograft survival. METHODS: Cardiac xenografts from male Hartley guinea pigs were heterotopically grafted into PVG (C-) and PVG (C+) male rats. Experimental animals received 20 mg/kg of NPC 15669 i.v. before cross-clamp release and 10 mg/kg of NPC 15669 intravenously on postoperative day 1. Control animals received intravenous saline solution only. RESULTS: Complement sufficient PVG (C+) rats rejected cardiac xenografts hyperacutely despite mode of treatment: PVG (C+) rats which received saline solution (n = 5) rejected their xenografts at 10.8 +/- 2.6 minutes, and those receiving NPC 15669 (n = 5) rejected at 13.9 +/- 5.3 minutes. Histologic examination showed edema, platelet aggregation, and hemorrhage but no cellular inflammatory infiltrate. As expected, complement-deficient PVG (C-) rats had markedly longer xenograft survival in the saline solution-treated group (n = 5) with graft function being sustained 14.7 +/- 6.1 hours. NPC 15669 treatment (n = 4) further prolonged graft function to 61.0 +/- 4.7 hours. In addition to edema, platelet aggregation, and hemorrhage, histologic analysis of these grafts at the time of rejection was characterized by an infiltration of neutrophils. CONCLUSIONS: We conclude that neutrophils play a critical role in cardiac xenograft rejection when complement activation is restricted. Combined inhibition of complement and neutrophil adhesion prolongs xenograft survival longer than inhibition of either component alone.

Ocular cicatricial pemphigoid with granular IgA and complement deposition.

A 65-year-old woman developed chronic redness of both eyes, and, over the ensuing 2 1/2 years, she had progressive conjunctival scarring with symblepharon formation. Other mucosal surfaces were not involved. A conjunctival biopsy specimen 12 months following onset of her disease showed areas of epithelial separation from the basement membrane zone as well as subepithelial chronic inflammation and scarring. Two years later, another conjunctival biopsy specimen showed granular deposition of IgA and C3 along the epithelial basement membrane zone using direct immunofluorescent staining. Electron microscopy confirmed the presence of deposits that were morphologically consistent with antigen-antibody complexes. These findings suggest that antigen-antibody (IgA) immune-complex deposition may provide an alternative pathogenetic mechanism to basement membrane zone autoantibody formation for development of progressive conjunctival scarring.

Pyoderma gangrenosum involving the eyelid.

A 62-year-old man was seen with an ulcer of the left upper eyelid of two weeks' duration. Over the previous 40 years, similar ulcers had intermittently developed elsewhere on his skin and spontaneously resolved over several months leaving atrophic scars. A biopsy specimen of the eyelid lesion showed epidermal ulceration with acute inflammation and liquefactive necrosis of the underlying dermis. Microorganisms and vasculitis were not present. On the basis of the clinical history and a compatible biopsy specimen, the diagnosis of pyoderma gangrenosum was made. This is an uncommon, idiopathic, ulcerating skin disease that may also have ocular manifestations. Eyelid ulcers have not previously been reported, to our knowledge. The diagnosis is established by clinical history and exclusion of other causes of ulceration.

Immunohistochemical analysis of the pathogenesis of posterior polymorphous dystrophy.

The pathogenesis of posterior polymorphous dystrophy was analyzed by immunohistologic methods. Sections of corneal buttons from two patients undergoing transplantation owing to posterior polymorphous dystrophy were stained with 2B4.14.1, a monoclonal antibody that reacts with human corneal endothelium, and with a cocktail of antihuman cytokeratin monoclonal antibodies that do not react with normal corneal endothelium. Single-stained sections revealed a variegated, intermittent staining pattern of antibody reactive and nonreactive cells. Double-stained sections revealed some cells that stained with only one of the antibodies and many cells that stained with both antibodies. The presence of cells staining positively for both 2B4.14.1 antigen and cytokeratins supports the hypothesis that the cytokeratin-expressing epithelial-like cells found in corneas with posterior polymorphous dystrophy arise via a metaplastic process in which the phenotype of endothelial cells becomes progressively abnormal.

Lymphocytotoxicity crossmatch proficiency testing among regional transplant centers.

During an eight and a half-year period (1976-1984), 408 combinations of different cells and sera involving 12,652 lymphocytotoxicity crossmatch reactions performed by 21-37 histocompatibility laboratories were studied in 20 proficiency tests conducted by the South-Eastern Organ Procurement Foundation. Consensus by 75% or more laboratories were obtained on 336 (82.4%) of these test samples: of the 10,410 reactions examined with the use of these consensus cells and sera, only 649 (6.2%) were discordant. Considering positive and negative reactions separately, the discordant (false) positive and negative rates were similar (6.1%, 6.4%, respectively). Varying specific factors in given tests indicated that discordant results were significantly reduced by (1) dispensing sera in trays centrally rather than locally; (2) using a standard one-wash procedure rather than local or three-wash methods; and (3) using reagent (monospecific) rather than patient (polyspecific) sera. Use of standard versus local rabbit complement did not significantly influence the concordance of results.

Histopathologic and immunochemical features of lattice corneal dystrophy type III.

We examined seven corneas from five patients with a new form of lattice corneal dystrophy (designated lattice corneal dystrophy type III) by light and electron microscopy. Numerous amyloid deposits were scattered throughout the corneal stroma, some of which were much larger than those usually observed in either lattice corneal dystrophy type I or II; these were located predominantly midway between the epithelium and the endothelium. Image analysis disclosed that the cross-sectional size of the large stromal amyloid deposits was significantly greater than those in age-matched patients with lattice corneal dystrophy type I. All patients had a discontinuous band of amyloid (15 to 25 micron wide) in the superficial stroma beneath Bowman's layer, which usually had only one or two small disruptions. Descemet's membrane and the endothelium were normal. The stromal deposits, which were composed of 10-nm diameter fibrils typical of amyloid, stained positively with Congo red after the histologic sections were pretreated with dilute potassium permanganate. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissue indicated that only some deposits reacted weakly with antibodies to amyloid protein AA. The deposits stained positively with antibodies to protein AP and negatively with antibodies to kappa and lambda immunoglobulin light chains.

Histopathologic features of rejecting orthotopic corneal xenografts.

Discordant xenogeneic Hartley guinea pig corneal buttons were transplanted orthotopically to either naive or pre-immune Lewis rats. Recipients were sacrificed serially and grafts were immediately frozen and subsequently examined using standard immunohistologic techniques. Corneal xenografts remained clear in naive recipients for 7 days, at which point they rapidly became opaque and edematous. In pre-immunized recipients, corneal xenografts were rejected much more quickly, becoming opaque and edematous by day 3 post-transplantation. Histologic examination of grafts revealed severe stromal edema and diffuse inflammatory cell infiltrates composed of mononuclear cells and neutrophils. Infiltrates were present as early as day 2 in xenografts from both presensitized and naive recipients. The infiltrates were densest in the posterior half of the grafts with fewer cells penetrating into the epithelium. Immunoperoxidase staining confirmed the presence of OX-19+ T cells as well as a substantial infiltrate of OX-42+ neutrophils/macrophages. Additionally, IgG was deposited throughout the grafts in a diffuse manner. Deposition of IgG was accelerated in presensitized recipients, with intense staining of the entire graft detected by day 2. Examination of the rejected grafts suggests that rejection occurs via mechanisms similar to those seen in corneal allografts. This, in turn, implies corneal xenografts may be amenable to standard immunosuppressive regimens.

Duplex Doppler sonography of renal transplants: lack of sensitivity and specificity in establishing pathologic diagnosis.

Recent reports have suggested the value of duplex Doppler sonography in the assessment of renal transplant function. Accurate diagnosis of acute rejection and its distinction from acute tubular necrosis and cyclosporine A toxicity have been claimed. We undertook a combined retrospective and prospective analysis of duplex Doppler examinations performed over a 2-year period to assess the value of such studies in evaluating renal allograft dysfunction. Seventy-seven sonographic examinations were performed on 77 renal transplants. A mean resistive index was calculated from Doppler measurements within main, segmental, and interlobar renal arteries by using the following ratio. peak systolic blood-flow velocity--minimum end-diastolic blood-flow velocity/peak systolic blood-flow velocity Forty-eight Doppler results were correlated with transplant biopsies and 29 with clinical course. Twenty-three episodes of acute allograft rejection were confirmed. When a resistive index of greater than or equal to 0.9 was used to indicate acute rejection, sonography had a sensitivity of only 9% and a specificity of 91% for this diagnosis. In one of eight cases of cyclosporine A toxicity and in three of six examples of acute tubular necrosis, the resistive index was greater than 0.9. In all six instances of chronic rejection, the resistive index was less than 0.84. None of eight patients with evidence of infection had a resistive index greater than 0.9. The resistive index range of 12 normally functioning allografts was 0.57-0.69. Correlation between the resistive index and the severity of arterial and arteriolar changes on biopsy was poor. An increased resistive index of renal transplant blood flow, as measured by duplex Doppler sonography, usually signals pathologic changes in an allograft. However, our data indicate that this test is not as sensitive or specific in identifying the cause of transplant dysfunction as has been suggested previously.

Identification of selective immunoglobulin a deficiency by renal biopsy.

We report three cases of selective immunoglobulin A (IgA) deficiency in which lack of direct immunofluorescent staining for IgA on renal biopsy specimens contributed to the diagnosis. In two patients, one with systemic lupus erythematosus and the other having asthma with nephrotic syndrome, the diagnosis of IgA deficiency was suggested by the complete absence of IgA on the renal biopsy. In the third patient, a renal transplant recipient, initial biopsies demonstrated donor-derived IgA, which disappeared on subsequent biopsies. The diagnosis of IgA deficiency was confirmed in all three patients by serologic quantification of IgA.