Clinical Significance of Antimonocyte Antibody in Kidney Transplant Recipients

Cerilli, G. James; Brasile, Lauren; Galouzis, Tom; DeFrancis, M E

doi:10.1097/00007890-198112000-00009

Cited by 39 publications

(10 citation statements)

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“…To understand further the mechanism(s} responsible for the development of proteinuria during rejection, precise information on the localization of glomerular immunoglobulins and/or immunoglobulin-antigen complexes is essential, and, therefore, currently under investigation in our laboratory. In agreement with other authors [22][23][24][25], we concluded that, although different mechanisms may effect proteinuria in chronic kidney rejection, in this study non-MHC alloantigens on vascular endothelial cells played a significant role in chronic rejection of MHC-matched or partly (class II) mismatched renal allografts.…”

Section: Discussionsupporting

confidence: 93%

Chronic renal allograft rejection: the significance of non-MHC alloantigens

Duijvestijn¹,

Vlek²,

Duistermaat³

et al. 1992

Transplant International

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We studied the role of polymorphic endothelial antigens other than MHC in antibody-mediated chronic renal allograft rejection in two models. In the first model, donor Lewis rat kidneys were transplanted into BN recipients that had been made tolerant for donor class I antigens at the B cell (antibody) level. In this setting Lewis kidney grafts were chronically rejected with stable renal function but increasing proteinuria ( > 100 mg/24 h). Rejected graft tissue showed mononuclear cell infiltration and the presence of glomerular vasculonecrotic lesions with fibrinoid material, associated with IgG and IgM deposition, but with absent or weak C3 binding. Graft endothelium showed no expression of MHC class II antigens. Serum antibodies were not reactive with donor class I antigens, but did react with endothelial non-MHC alloantigens. In the second model, more direct information on the role of endothelial non-MHC alloantigens in renal allograft rejection was obtained by transplanting Lewis 1 N kidneys into unmodified BN recipients (MHC-matched transplants). Here, similar to the first model, the animals developed severe proteinuria with stable renal function. Histopathological examination showed mononuclear cell infiltration and deposition of IgM and IgG along the glomerular vasculature, but this time in the presence of strong C3 reactivity. However, glomerular vasculonecrotic lesions with intense fibrin deposition were not observed. The data showed that although clinically the two kidney transplantation models used gave similar chronic rejection phenomena, histopathologically some striking differences were observed in the glomeruli. The precise mechanisms effecting chronic rejection of the grafts is still a puzzle. However, immune reactivity against graft ( endothelial) non-MHC antigens may play a significant role.

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Section: Discussionsupporting

confidence: 93%

Chronic renal allograft rejection: the significance of non-MHC alloantigens

Duijvestijn¹,

Vlek²,

Duistermaat³

et al. 1992

Transplant International

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“…Shared m<p-endothelial antigens may play a role in immunological injury such as that found in renal transplant rejection. Interest ingly, a significant percentage of renal transplant patients who reject the kidneys of HLA-identical donors develop antibodies with specificity for both monocytes and endo thelial cells [49,50], Moreover, in one study, 46% of patients with peripheral vascular disease compared to 10% of control patients demonstrated an autoantibody against their autologous monocytes and endothelial cells, which may be associated with the HLA antigen DRw6 [51]. Autoantibodies to monocytes and endothelial cells are also present in the sera of patients with rheumatic dis eases, such as vasculitis [51 ].…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Antibodies Defining Shared Human Macrophage-Endothelial Antigens

Koch¹,

Burrows²,

Domer³

et al. 1992

Pathobiology

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We have selected several monoclonal antibodies (mAbs) produced using human rheumatoid arthritis (RA) synovial macrophages (mφs) as immunogen. Of these, mAbs 8H2, 10G7 and 10G9 showed cross reactivity with endothelium, suggesting common antigens between these cell types. We have determined the spectrum of reactivity of these mAbs on hematopoietic cell lines, peripheral blood cells, and inflammatory and non-inflammatory tissues by immunohistochemistry. MAb 8H2 does not react with the myeloid cell lines HL60 (myelocytic), U937 (histiocytic lymphoma), and K562 (erythroleukemia), or with peripheral blood cells. In normal and inflamed tissue sections, MAb 8H2 reacts with mφs and endothelial cells. In contrast, mAb 10G7 does not react with peripheral blood cells, but reacts with HL60, U937, and K562 cell lines, as well as with mφs and endothelial cells in inflamed and nonin-flamed tissues. MAb 10G9 does not react with myeloid cell lines, but reacts with monocytes and platelets in peripheral blood. In both normal and inflamed tissues, MAb 10G9 reacts with mφs and endothelial cells. The antigens identified by these three mAbs were characterized biochemically, by enzymatic digestion of RA synovial tissue mφs followed by a cellular ELISA, as well as by reactivity of the mAbs with NIH-3T3 cells genetically engineered to express known myeloid antigens. These mAbs reacted with protein or glycoprotein antigens distinct from the known myeloid antigens CD 13, CD 14, CD33, CD34, CD36, and c-fms. These mAbs should prove to be a valuable tool for studying mφs and endothelial cells and their shared antigenic determinants.

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“…Related experiments using human kidney have not been performed. The significance of the recently reported endotheUal-monocyte (Cerilli et al 1981), and monocyte (Russ et al 1983) alloantigen systems also remains only poorly defined.…”

Section: Mhc Antigens In the Kidneymentioning

confidence: 99%

Analysis of Intragraft Effector Mechanisms Associated with Human Renal Allograft Rejection: Immunohistological Studies with Monoclonal Antibodies

Hancock

1984

Immunological Reviews

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Immunohistological studies of rejecting human renal allografts show that the onset of graft rejection is accompanied by the influx of small numbers of T-cells and macrophages. Both cell types occur in focal aggregates adjacent to the Class II antigen-rich renal vasculature and glomerular Bowman's capsule. Although most of the T-cells express the OKT8+ phenotype of cytotoxic T-cells, analysis with markers for activation of T-cells suggests that the vast majority of these cells are present as functionally inactive precursor cells. Smaller numbers of OKT4+ helper T-cells, NK cells and occasional B-cells are also present. Within a few days, up to 15% of T-cells express receptors for IL-2 and other activation markers, suggesting that they are now functionally active. OKT8+ T-cells continue to predominate, but at least some OKT4+ T-cells appear active as DTH cells. A large influx of mononuclear cells, particularly macrophages, follows and these cells are found within and adjacent to the large Class I antigen-rich intertubular capillary network. Many of these intragraft macrophage express pro-coagulant function, presumably through lymphokine-induced activation, and are enmeshed in a fibrin network. Irreversible kidney damage may result from the combined onslaught of these cellular and humoral mechanisms, and examination of nephrectomy specimens suggests that this destruction is principally mediated by macrophages and polymorphs. These studies, by showing the presence of multiple functionally active cell types within rejecting grafts, provide evidence for a multiplicity of intragraft effector mechanisms. This evidence indicates that in addition to cytotoxic T-cells, DTH cells, macrophages, NK, K and B cells contribute to the rejection process. Further unravelling of the complex response and, hence, greater insights into the basis for more effective immunosuppression are likely to follow from the immunohistological application of monoclonal antibodies to rejecting grafts. However, comparison with animal models of kidney rejection already suggests that there may be important differences in both the initiation and effector phases of human kidney allograft rejection.

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Clinical Significance of Antimonocyte Antibody in Kidney Transplant Recipients

Cited by 39 publications

References 0 publications

Chronic renal allograft rejection: the significance of non-MHC alloantigens

Chronic renal allograft rejection: the significance of non-MHC alloantigens

Monoclonal Antibodies Defining Shared Human Macrophage-Endothelial Antigens

Analysis of Intragraft Effector Mechanisms Associated with Human Renal Allograft Rejection: Immunohistological Studies with Monoclonal Antibodies

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