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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)

Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD.
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PMID:Immunohistochemistry of cutaneous graft-versus-host disease after allogeneic bone marrow transplantation. 193 60

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

Bone marrow transplantation is now an accepted component in the overall therapy of acute and chronic (myeloid) leukaemia for some selected patients. Some of the obstacles to success have been partially overcome. Many advances in supportive care have been made. Pneumocystis carinii and herpes simplex infections are preventable. Effective decontamination of the gastrointestinal tract for bacteria and fungi is now readily achievable and may have reduced the risk of serious systemic infections. New antibiotics which, in combination, are effective in life-threatening infections are under study. Recent developments in the prevention or amelioration of graft versus host disease (GvHD) have included T lymphocyte depletion in the donor marrow and the use of the fungal polypeptide cyclosporin A. Less than 10% of patients would now be expected to succumb to this complication. Outstanding problems remaining to be resolved are the improvement in the antileukaemic conditioning prior to transplantation and the prevention or treatment of cytomegalovirus infection in the seropositive recipient. This infection can cause pneumonitis and is currently the single most frequent transplant related cause of mortality.
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PMID:A review of the current status and techniques of allogeneic bone marrow transplantation for treatment of leukaemia. 635 92

T cell activation and cellular immune responses are modulated by interleukin 2 (IL2) through binding to its corresponding cell surface receptor. Three forms of the receptor are recognised based on IL2 binding affinity. The high affinity receptor is a heterotrimer composed of alpha, beta, and gamma(c)-polypeptide chains. The 55 kDa alpha-chain also known as the Tac (T cell activation) antigen or CD-25 is a unique subunit of the high affinity IL2 receptor (IL2Ralpha). Resting T cells express few IL2Ralpha, however, when activated, the expression of ILR2alpha rapidly increases. The IL2Ralpha is shed from the cell surface and is measurable in the serum as a 45 kDa soluble form (s-Tac or s-IL2Ralpha). Serum concentrations of s-Tac can be used as a surrogate marker for T cell activation and IL2Ralpha expression. IL2Ralpha is over expressed by T cells in a number of autoimmune diseases, allograft rejection and a variety of lymphoid neoplasms. IL2 induced proliferation of T cells can be inhibited by the murine monoclonal antibody (anti-Tac) directed against the alpha-chain of the IL2R. Through molecular engineering, murine anti-Tac has been humanised reducing its immunogenicity without changing its specificity. Humanised anti-Tac (HAT) has been shown to reduce the incidence of renal and cardiac allograft rejection as well as decrease the severity of graft versus host disease in patients undergoing HLA matched allogeneic bone marrow transplantation. IL2Ralpha targeted treatment with radioimmunoconjugates of anti-Tac and immunotoxins has shown promise in the treatment of CD25 expressing lymphomas.
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PMID:Advances in interleukin 2 receptor targeted treatment. 1105

CD8(+) T cells are key mediators of transplant rejection and graft-versus-host disease and contribute to the pathogenesis of autoimmune diseases. We tested whether TCR ligands can be converted into T cell activation receptors, redirecting genetically modified T cells at pathogenic CD8(+) T cells. For this purpose we exploited the ability of the non-polymorphic beta(2) microglobulin light chain to pair with all MHC class I heavy chains. In this report we describe the design and expression in a T cell hybridoma of two modalities of beta(2) microglobulin polypeptides, fused with the transmembrane and intracellular portion of CD3zeta chain. In the absence of a particular antigenic peptide, the chimeric product associates with different endogenous MHC class I heavy chains and triggers T cell activation upon heavy chain cross-linking. When an antigenic peptide is covalently attached to the N-terminus of the chimeric polypeptide, transfectants express high level of surface peptide-class I complexes and respond to antibodies and target T cells in a peptide-specific manner. Our results provide the basis for a universal genetic approach aimed at antigen-specific immunotargeting of pathogenic CD8(+) T cells.
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PMID:Chimeric beta2 microglobulin/CD3zeta polypeptides expressed in T cells convert MHC class I peptide ligands into T cell activation receptors: a potential tool for specific targeting of pathogenic CD8(+) T cells. 1456 36

A phase 1 diagnostic study was performed to evaluate a novel technology for clinical proteomic research based on capillary electrophoresis and mass spectrometry. Urine from 40 patients after hematopoietic stem cell transplantation (HSCT; 35 allogeneic, 5 autologous) and 5 patients with sepsis was collected for a period of 100 days and analyzed. More than 1000 different polypeptides could be detected in individual samples. Polypeptide patterns excreted in the urine of patients were significantly different from those of healthy volunteers. No significant differences were detected comparing different conditioning regimens. The aim of this study was to identify polypeptide patterns functioning as early indicators of graft-versus-host disease (GVHD). Eighteen patients developed GVHD after allogeneic HSCT. Sixteen differentially excreted polypeptides formed a pattern of early GVHD markers, allowing discrimination of GVHD from patients without complications with 82% specificity and 100% sensitivity, cross-validated. Inclusion of 13 sepsis-specific polypeptides allowed us to distinguish sepsis from GVHD with a specificity of 97% and a sensitivity of 100%. Sequencing 2 prominent GVHD-indicative polypeptides led to the identification of a peptide from leukotriene A4 hydrolase and a peptide from serum albumin. The data reveal that capillary electrophoresis and mass spectrometry allow identification of biomarkers for a variety of diseases or related complications.
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PMID:Proteomics applied to the clinical follow-up of patients after allogeneic hematopoietic stem cell transplantation. 1505 46

Colostrum and milk are rich in proteins and peptides which play a crucial role in innate immunity when transferred to the offspring and may accelerate maturation of the immune system in neonates. The immunotropic properties of these proteins prompted investigators research their potential application in prevention and therapy. Lactoferrin (LF) exhibits antibacterial, antifungal, antiviral, antiparasitice, and antitumoral activities. It is protective with regard to intestinal epithelium, promotes bone growth, and accelerates the recovery of immune system function in immunocompromised animals. LF was tried in the treatment of hepatitis C infection and the intestinal form of graft-versus-host disease (GvHD). A proline-rich polypeptide (PRP) demonstrated a variety of immunotropic functions, including the promotion of T-cell maturation and inhibition of autoimmune disorders. PRP, in the form of chewable tablets (Colostrinin) was recently found to improve or stabilize the health status of Alzheimer's disease patients. Casein and casein-derived peptides showed protective activities in enamel demineralization and as caries-preventing agents. The protein hydrolyzates were also protective in diabetic animals, reduced tumor growth, had antihypertensive activity and diminished colicky symptoms in infants. Glycomacropeptide (GMP), a peptide derived from kappa-casein, exhibited various antibacterial and antithrombotic activities. Alpha-lactalbumin (LA) demonstrated antiviral, antitumoral and anti-stress properties. LA-enriched diets were anxiolytic, lowered blood pressure in rats, prevented diarrhea, and led to a better weight gain in malnourished children. HAMLET, a complex of LA and oleic acid, was effective in patients with cutaneous papillomas. Lysozyme found application in infant formulas, the treatment of periodentitis, and the prevention of tooth decay. Milk enriched in lysozyme was used in feeding premature infants suffering from concomitant diseases. Interesting, antibacterial properties were exhibited by lactoperoxidase. Both lysozyme and lactoperoxidase required cooperative action with LF in combating bacteria. In conclusion, preparations derived from milk and colostrum are effective, easily bioaccessible, and safe, finding wide application in prevention and therapy for newborns and adults.
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PMID:[Therapeutic properties of proteins and peptides from colostrum and milk]. 1599 98

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for the treatment of leukemia and other immunogenetic disorders. The use of tolerogenic dendritic cells (DCs) with potent immunoregulatory properties by inducing the generation/activation of regulatory T cells (Tr) for the treatment of acute GVHD following allogeneic BMT has been recently established. Here we report the use of the known immunosuppressive neuropeptide, vasoactive intestinal polypeptide (VIP), as a new approach to inducing tolerogenic DCs with the capacity to prevent acute GVHD. DCs differentiated with VIP impair allogeneic haplotype-specific responses of donor CD4+ T cells in transplanted mice by inducing the generation of Tr in the graft. Importantly, VIP-induced tolerogenic DCs did not abrogate the graft versus leukemia response, probably because they do not abrogate cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the inclusion of VIP-induced tolerogenic DC in future therapeutic regimens may facilitate the successful transplantation from mismatched donors, reducing the deleterious consequences of acute GVHD, extending the applicability of BMT.
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PMID:Vasoactive intestinal polypeptide induces regulatory dendritic cells that prevent acute graft versus host disease and leukemia relapse after bone marrow transplantation. 1688 71

Endothelial monocyte-activating polypeptide-II (EMAP-II) appears to play an important role in neovascularization and endothelial abnormalities. However, the role of EMAP-II in development of graft-versus-host disease (GVHD) after allogeneic SCT is poorly understood. We measured and compared the levels of EMAP-II, cytokines, and soluble factors in patients undergoing allogeneic SCT. The subjects were 23 patients who underwent allogeneic SCT. Most of the cytokines/soluble factors exhibited a significant elevation after allogeneic SCT, although Angiopoietin-1 did not change. On the other hand, the levels of these factors did not change significantly in the recipients of autologous SCT. When the relationship between EMAP-II and cytokines/soluble factors was analyzed, EMAP-II levels correlated positively with sIL-2R, sVCAM-1, sE-selectin, sFasL and EDMP. However, IL-6, Angiopoietin-1, Angiopoietin-2 and VEGF were not correlated with EMAP-II. Our results suggest that EMAP-II plays an important role in endothelial cell dysfunction related to GVHD after allogeneic SCT.
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PMID:The significance of EMAP-II after allogeneic stem cell transplantation. 1956 73

The fetal semi-allograft can induce expansion and tolerance of antigen-specific maternal T and B cells through paternally inherited major histocompatibility complex and minor histocompatibility antigens (mHAgs). The effects of these antigens have important consequences on the maternal immune system both during and long after pregnancy. Herein, we investigate the possibility that the placental syncytiotrophoblast and deported trophoblastic debris serve as sources of fetal mHAgs. We mapped the expression of four mHAgs (human mHAg 1, pumilio domain-containing protein KIAA0020, B-cell lymphoma 2-related protein A1, and ribosomal protein S4, Y linked) in the placenta. Each of these proteins was expressed in several placental cell types, including the syncytiotrophoblast. These antigens and two additional Y chromosome-encoded antigens [DEAD box polypeptide 3, Y linked (DDX3Y), and lysine demethylase5D] were also identified by RT-PCR in the placenta, purified trophoblast cells, and cord blood cells. Finally, we used a proteomic approach to investigate the presence of mHAgs in the syncytiotrophoblast and trophoblast debris shed from first-trimester placenta. By this method, four antigens (DDX3Y; ribosomal protein S4, Y linked; solute carrier 1A5; and signal sequence receptor 1) were found in the syncytiotrophoblast, and one antigen (DDX3Y) was found in shed trophoblast debris. The finding of mHAgs in the placenta and in trophoblast debris provides the first direct evidence that fetal antigens are present in debris shed from the human placenta. The data, thus, suggest a mechanism by which the maternal immune system is exposed to fetal alloantigens, possibly explaining the relationship between parity and graft-versus-host disease.
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PMID:Minor histocompatibility antigens are expressed in syncytiotrophoblast and trophoblast debris: implications for maternal alloreactivity to the fetus. 2207 31


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