Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of numerous keratin bodies in the upper dermis is a characteristic finding in skin lesions of patients with various dermatoses such as cutaneous graft-versus-host disease, lichen planus, or chronic discoid lupus erythematosus. These keratin bodies are generated by apoptotic keratinocyte death, consist largely of keratin intermediate filaments (KIF), and are constantly covered with immunoglobulins, mainly IgM. Apoptosis is also thought to occur under physiologic conditions in the skin as it does in other organs, but keratin bodies are not frequently reported as being found in nonlesional skin. In order to assess the frequency of keratin bodies in normal skin, we examined serial sections of 10 normal human skin specimens and 5 dermal sheets prepared from normal human skin for the presence of keratin bodies. They were visualized by direct immunofluorescence using a fluorescein isothiocyanate (FITC) rabbit antihuman IgM conjugate. In addition the KIF origin of keratin bodies was demonstrated by a double-staining immunofluorescence procedure using a FITC-conjugated rabbit antihuman IgM followed by a mouse monoclonal antibody against keratin and a sheep antimouse immunoglobulin conjugated with Texas Red. One specimen was also examined for keratin bodies at the ultrastructural level. In serial sections, all 10 normal human skin specimens had numerous keratin bodies as assessed by visualization of globular IgM deposits. Evaluated on dermal sheets, the number of keratin bodies ranged from 39-262 per mm2. Nearly all keratin bodies also stained with the antikeratin antibodies. Ultrastructurally the remarkable number of keratin bodies, which consist of filaments measuring approximately 10 nm in diameter or of more granular material, in normal human skin was confirmed. In order to investigate the capacity of KIF material in keratin bodies to function as autoantigen, we examined the sera of the 10 skin donors and, in addition, of 30 normal healthy individuals and 10 patients with rheumatoid arthritis for the occurrence and specificity of IgM-anti-KIF autoantibodies by an enzyme-linked immunosorbent assay and by immunoblot. IgM-anti-KIF autoantibodies were found in all 50 test sera. In the majority of the sera the specificity of these autoantibodies included the 51 kD and the 58 kD KIF protein, which are constituents of KIF in keratin bodies and basal keratinocytes. Quantitatively, the antibody activity of the IgM-anti-KIF autoantibodies varied from serum to serum, being highest in the sera of patients with rheumatoid arthritis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Apoptotic keratin bodies as autoantigen causing the production of IgM-anti-keratin intermediate filament autoantibodies. 242 83

IgG-anti-keratin intermediate filament autoantibodies occur in low titers in all normal human sera. These same antibodies are present in high titers in the sera of patients who have diseases in which cells containing keratin intermediate filaments (KIF) have been damaged, such as systemic lupus erythematosus, graft-versus-host disease, and cutaneous tumors. Since some human autoantibodies are thought to function in part as opsonins promoting the removal of insoluble cellular proteins after tissue injury, we investigated the influence of IgG-anti-KIF autoantibodies on the phagocytosis of insoluble KIF aggregates by human monocytes and polymorphonuclear neutrophils (PMN). Keratin intermediate filaments assembled in vitro were reconstituted into dense spherical KIF aggregates 0.3-2.5 microns in diameter by dialysis against phosphate-buffered saline. Immunoelectron microscopy revealed that, as expected, human IgG-anti-KIF autoantibodies bound to the KIF aggregates. Human monocytes or PMN were incubated either with nonopsonized KIF aggregates or with KIF aggregates that had been reacted with IgG-anti-KIF autoantibodies. The uptake of KIF aggregates was visualized by indirect immunofluorescence, immunoperoxidase staining, and immunoelectron microscopy. Monocytes rapidly and efficiently bound and phagocytosed KIF aggregates that had been coated with IgG-anti-KIF autoantibodies. Nonopsonized KIF aggregates, in contrast, were taken up much less efficiently. Differences were most marked at 4 degrees C for 60 min with phagocytosis of opsonized KIF aggregates by 23 +/- 8% of monocytes in contrast to phagocytosis by only 0.2 +/- 3% monocytes when nonopsonized KIF aggregates were used. Similar results occurred at 37 degrees C for 5 min with phagocytosis by 38 +/- 28% vs 1.8 +/- 0.4% of monocytes of opsonized and nonopsonized KIF aggregates, respectively. A high percentage of PMN also phagocytosed opsonized KIF aggregates, whereas nonopsonized KIF aggregates were ingested less avidly. These data indicate that the opsonization of extracellular KIF aggregates by IgG-anti-KIF autoantibodies plays an important role in promoting the phagocytosis of KIF aggregates. The subsequent phagocytosis represents a rapid and very effective mechanism for the removal of insoluble KIF following keratinocyte cell death.
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PMID:Phagocytosis of keratin filament aggregates following opsonization with IgG-anti-keratin filament autoantibodies. 243 55

A comparative study of the healthy skin of patients who had undergone bone marrow grafting and not developed graft-versus-host disease (GVHD) and of patients with cutaneous lesions of acute GVHD has been carried out. The aim of this study was to assess the diagnostic value of cutaneous immunopathology in the diagnosis of acute GVHD. A double-labelling immunofluorescence technique was used with a panel of monoclonal antibodies. The results showed a lack of specificity for GVHD in the distribution of Langerhans cells, but confirmed the diagnostic value of HLA-DR staining of epidermal keratinocytes. Cellular polymorphism of the T cell infiltrate in the dermis was observed (T helpers 40% and T suppressors 20%). The expression of the 55-57 Kd keratin polypeptide and of bullous pemphigoid antigen showed modification during acute GVHD while that of pemphigus antigen remained unchanged.
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PMID:Cutaneous immunological studies in diagnosis of acute graft-versus-host disease. 351 Jun 54

It has been suggested that the bulge of the hair follicle contains a pool of follicular stem cells that may serve as a target site of graft-versus-host disease and as a source of cells with carcinogenic potential. The bulge is prominent in the developing follicle although it is a subtle swelling in the adult follicle. In this paper, we studied the bulge in human fetal skin specimens. Ultrastructurally, the bulge cells, especially the interior cells, have abundant free ribosomes and glycogen particles, but almost no cytoplasmic organelles indicative of differentiation. Immunostaining with several specific anti-keratin antibodies demonstrated that the bulge cells express keratins of both stratified and simple epithelia. Melanocytes and Merkel cells, defined by immunohistochemical and ultrastructural criteria, are seen among bulge cells. Laser confocal microscopy revealed that primitive smooth muscle cells attached directly to the bulge initially at the mid-bulbous hair peg, the stage when the bulge is most prominent. K-laminin and type VII collagen are strongly expressed in the dermoepidermal junction of the bulge and between the matrix area of the bulb and the dermal papilla. Thus, the bulge of human hair follicle is not only an attachment site for arrector pili muscle, but also a pool of keratinocytes that are relatively undifferentiated.
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PMID:Characterization of hair follicle bulge in human fetal skin: the human fetal bulge is a pool of undifferentiated keratinocytes. 749 Apr 81

When graft-versus-host (GVH) disease affects the liver, it is characteristically the bile ducts which are involved, infiltrated by lymphocytes. To characterize this process further, and to determine whether there were any antigenic changes in the bile ducts, we stained 9 liver biopsies involved by GVH disease, 10 non-GVH biopsies that had a prominent portal lymphocytic component, and 8 biopsies taken incidentally at surgery for noninflammatory liver disease with epithelial membrane antigen, AE-3, AE-1, a keratin cocktail, keratin 19, CD45RO (UCHL-1), CD43 (Leu-22), CD20 (L26), vimentin, and LN-3. The infiltrating lymphocytes were T cells (CD45RO+, CD43+, CD20-) which variably expressed LN-3. The bile ducts were positive for the keratin cocktail, AE-1, AE-3, and keratin-19, but only occasionally positive for EMA and LN-3. There was no significant difference in the staining patterns of either the bile duct cells or lymphocytes between the three groups. With the antibodies that we used, there does not appear to be a significant difference in the antigenic phenotype of the bile ducts in GVH as compared to normal or reactive livers.
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PMID:Phenotype of bile ducts and infiltrating lymphocytes in graft-versus-host disease. 768 95

Nine marrow allograft recipients who developed GVHD of the gastrointestinal tract accompanied by the passage of ropey necrotic material per rectum were studied. The material, resembling necrotic intestinal mucosa, was evaluated for the presence of epithelial cells using monoclonal antibodies for keratin and macrophages. Two keratins (AE1/AE3 and 34 beta E12) were detected within cells in all cases while macrophages were found in all but one case. In three cases, some cells were positive for both antibodies suggesting the presence of phagocytosed keratin in macrophage cytoplasm. Search for organisms with Gram and methenamine silver stains showed bacteria in six cases and fungus in one. Some cases of severe GVHD will be associated with the passage of ropey tan material grossly resembling sloughed mucosal tissue, but microscopically consisting largely of fibrin clots. The presence of free intestinal epithelial cells in this material is confirmed by the present study.
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PMID:Positive identification of enterocytes by keratin antibody staining of sloughed intestinal tissue in severe GVHD. 769 Jun 32

The identity of cells within squamous epithelia that represent primary targets in acute graft-versus-host disease (GVHD) has been an enigma. Murine effector T cells implicated in the alloresponse by Vbeta complementarity-determining region-3 spectratype analysis were detected with a Vbeta-specific monoclonal antibody within discrete microdomains of tongue (lingual) squamous epithelium. These microdomains, termed rete-like prominences (RLPs), are similar to the rete ridges of human skin. Cells forming the basal layer of RLPs and of human skin rete ridges were shown to express a distinctive pattern of keratin expression defined by antibodies to cytokeratin 15 (K15). In experimental murine GVHD elicited across minor histocompatibility antigen barriers (miHA), early lesions involved selective apoptosis and loss of K15(+) staining within lingual RLPs. An in vitro organ culture model designed to investigate target cell injury by short-term exposure to tumor necrosis factor-alpha and interleukin-1beta, mediators relevant to GVHD, showed a similar pattern of apoptosis and loss of K15(+) reactivity within RLPs. In aggregate, these findings establish a novel cytoskeletal marker for target epithelial subpopulations that should facilitate evaluation of mechanisms of host cell injury in GVHD. These data may also enable the development of therapeutic approaches to abrogate disease at the level of target cell blockade.
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PMID:An epithelial target site in experimental graft-versus-host disease and cytokine-mediated cytotoxicity is defined by cytokeratin 15 expression. 1450 58

Black hairy tongue (BHT) is an unusual condition in adults characterized by marked accumulation of keratin on the dorsum of the tongue, resulting in a hair-like appearance. Herein, we have described 15 patients developing BHT after allogeneic stem cell transplantation (allo-SCT). BHT was generally accompanied by other cutaneous manifestations of cutaneous graft-versus-host disease (GVHD) or a precursor of GVHD. Our experience in this series emphasized that histopathologic evaluation is required for seemingly harmless eruptions like BHT in the posttransplantation period. Given the important prognostic implications of GVHD, physicians should be careful when confronted with BHT.
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PMID:Black hairy tongue after allogeneic stem cell transplantation: an unrecognized cutaneous presentation of graft-versus-host disease. 2116 45

Keratins are proteins that form intermediate filaments of epithelial cell cytoskeleton. The utility of keratin expression determination is based on the fact that epithelial cells acquire a specific pattern of keratin expression during differentiation and maturation, which reflects the specificity of the tissue and the degree of maturation, and generally remains stable during carcinogenesis. Determination of the pattern makes it possible to identify the origin of cells in diagnosing neoplastic lesions as well as in research on pathophysiology or the possibility to apply keratin-positive cell detection in the process of cancer staging and treatment planning. As keratins undergo degradation during apoptosis as caspase substrate the identification of the caspase-derived K18 fragment by the use of specific monoclonal antibody allows us to estimate the apoptosis/necrosis ratio, especially in liver pathology, e.g. nonalcoholic steatohepatitis, chronic hepatitis or graft-versus-host disease or in assessing response to antiviral or antitumour therapy.
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PMID:Cytokeratins in gastroenterology. Systematic review. 2655 35