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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 small intestine is a well documented target organ in mouse and human GVHD, and diarrhea is a prominent part of the clinical GVHD syndrome. Although a plethora of systemic immune deficits has been documented in GVHD, the integrity of the small intestinal immune system has not been investigated. A correlation has not been demonstrated between systemic immune dysfuction and the incidence of lymphomas in mouse GVHD survivors. If gastrointestinal immune deficiency exists in mouse GVHD, its possible relationship to GVHD lymphomas, frequently abdominal. should be investigated. GVHD was produced in newborn BLA (C57 BL/Ka females x BALB-C males) mice house in a specific pathogen-free environment by the i.p. inoculation of 10(7) male BALB-C spleen cells. Control mice received syngeneic spleen cells. Twenty GVHD and 16 control mice were sacrificed at 3 weeks and specimens of duodenum were removed for routine histologic and immunofluorescent examination. All but one GVHD mouse (95%) had virtually absent duodenal IgA and IgM. Duodenal cellular fluorescence was demonstrated in all controls. A significant duodenal immunoglobulin deficit has been demonstrated in 3-week-old GVHD mice. The relationship of this finding to GVHD diarrhea, wasting, and neoplasia remains to be determined.
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PMID:Duodenal immunoglobulin deficiency in graft versus host disease (GVHD) mice. 0 29

Mice homozygous for the recessive mutation motheaten (me) are deficient in capacity for immune response but show an elevated level of serum immunoglobulins. In comparison to spleen cells from normal sibs, spleen cells from me/me mice have a severely depressed 19S PFC response to SRBC. In the GVH assay, spleen and thymus cells from motheaten donors caused significantly weaker reactions than like cells from normal sibs. Serum electrophoretic patterns of motheaten mice showed increased levels of alpha-, beta-, and gamma-globulins and decreased levels of albumin. Increases in quantities of all major classes of immunoglobulins were found in serum of me/me mice 5 weeks of age and older. Elevation of serum IgM was evident by 3 weeks of age and had reached 25 times the levels in normal sibs by 6 weeks of age. Immunoelectrophoresis and Ouchterlony analysis showed motheaten serum to have both kappa and lambda2 light chains. Evidence of autoimmunity was found in motheaten mice in the granular deposition of IgM and IgG in kidney glomeruli. Motheaten mice, thus, appear to have a severe immune deficiency, but the basic nature of the deficiency is not yet known.
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PMID:Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins. 5 6

Cytomegalovirus infection in compromised hosts occurs most frequently as asymptomatic shedding of a reactivated virus. Reactivation occurs when cellular immunity is compromised owing to either immune-deficiency disease or iatrogenic intervention. When intervention is modest, most antibody-positive patients do not shed virus (19); when the group is treated with a higher mean dose of cytotoxic agents, almost all antibody-positive patients shed virus (6). In the instance where the chemotherapeutic program includes massive doses of these agents, as in heart or marrow transplantation, or when dysfunction of all cellular activity is extreme, as in the case of severe combined immune deficiency and far-advanced neoplasia, dissemination of infection with multiple-organ involvement ensues (17, 20-22). Primary infection may occur in some patients with neoplasia or in marrow-transplant recipients from either blood transfusions or from marrow, although data are insufficient to be certain (22). It has been conclusively shown, however, that seronegative renal-allograft recipients usually develop primary infection when they acquire a kidney from a seropositive donor. Clinical illness related to virus infection in the first few months after transplantation occurs in almost all patients with primary infection and seldom in those with reactivation infection (6, 25, 26). Three very intriguing observations have been made that should suggest avenues for future research: (a) Since illness occurs more closely related to development of antibody than it does to onset of virus shedding, this suggests that host response plays an important role in the disease that is obviously caused by a virus; a definition of the mechanism of this interaction could lead to an understanding of host-induced disease processes in man; (b) Graft-versus-host disease in marrow transplantation; and (c) allograft rejection in renal-graft recipients correlate with development of CMV infection (16, 22, 24, 26). Taken together, these observations are consistent with the hypothesis that virus antigens interrelate with most antigens in such a way as to lead to immune response to both antigens. Exploration of this clinical observation could lead to a greater understanding of the function of the HL-A system in man.
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PMID:Cytomegalovirus (CMV) in the compromised host(s). 19 29

Bone marrow transplantation is a major therapeutic approach for treatment of patients with severe aplastic anemia or acute leukemia refractory to chemotherapy. It is possible only if an HLA matched sibing is found. ABO compatibility is not necessary. The conditionning regimen includes high doses of cyclophosphamide associated or not with a 1 000 rads total body irradiation. In acute leukemia, the two year percentage survival is 17%, in aplastic anemia it is 40%. Complications are immunologic : rejection, graft versus host disease and persistent severe immune deficiency.
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PMID:[Allogenic bone marrow grafts (author's transl)]. 32 42

A chimeric model consisting of severe combined immune deficiency (SCID) mice populated with human peripheral blood leukocytes (PBL) has recently been described (bu-PBL-SCID mice). These reports indicated a limited reconstruction of the transferred human immune system and functionality of the human graft. Herein we described modifications of the PBL transfer method that minimize transfer time and cellular manipulations, leading to a more effective population of SCID mouse recipients. Severe combined immune deficiency mice given 15 x 10(6) PBL had human IgG serum levels reaching 2 to 5 g/l, and all mice had detectable human anti-tetanus toxoid antibody levels when they received cells from donors with such levels. These transfers were associated also with clinical and histologic evidence of graft-versus-host disease, suggesting responsiveness of the human graft in the recipients. When Epstein-Barr virus seropositive (EBV+) donors were used, the chimeric mice also showed a high incidence of fatal lymphoproliferative disease 1 to 3 months after transfer of 15 x 10(6) PBL. The high level of immunoglobulin synthesis and immunoresponsiveness of the human cells with this transfer procedure may expand the use of these chimeric mice for the manipulations of human immune cells in vivo.
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PMID:Characterization of hu-PBL-SCID mice with high human immunoglobulin serum levels and graft-versus-host disease. 133 84

Use of allogeneic bone marrow transplants continues to increase. During the 36-year period between 1955 and 1990, more than 33,000 patients received allogeneic bone marrow transplants; more than 45% of these were performed during the 3 years 1988-1990. Transplants are effective therapy for leukemia and other hematologic diseases. It is widely considered that transplants are the treatment of choice for aplastic anemia and chronic myelogenous leukemia, those who fail conventional therapy for acute leukemia and a variety of genetic, metabolic and immune deficiency disorders. Successful application of bone marrow transplantation is limited by complications such as graft failure, graft versus host disease GVHD and interstitial pneumonia and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants were performed using unrelated or HLA-partially matched related donors with some success. Development of post-transplant complications can often be predicted by risk factor assessment. In this report, current data from the IBMTR are summarized and several risk factors affecting outcome identified.
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PMID:Current status of allogeneic bone marrow transplantation. 142 Oct 39

The observation that malignant cells express antigens that may be recognized by immunocytes and that immune effector mechanisms have the capability of destroying tumor cells has increased our appreciation of the biology of cancer and its relationship to immune function as well as offered new options for therapeutic intervention. Clinical trials are in progress to evaluate several different approaches to modifying the host's immune response against tumor. One approach is to administer agents that have direct activity against the malignancy. For example, antibody conjugates bring cytotoxic molecules of chemotherapy, radioisotopes, or toxins directly to the tumor. A second approach is to administer agents that modulate the host's own antitumor response such as IFN-alpha and IFN-gamma. Adoptive cellular immunotherapy aimed at isolating and expanding the host's own tumor-specific lymphocytes and inducing activation and proliferation with lymphokines such as IL-2 has shown encouraging results. Even though clinical data are still quite premature, it is reasonable to assume that in the future immunomodulation including the stimulation of immune effector mechanisms to eradicate tumor, the reconstitution of immune deficiency in diseases such as AIDS, the suppression of immune function to avoid graft rejection and GVHD, and the isolation and insertion of genes encoding tumor antigens into recombinant vectors to immunize the host to the tumor antigen will be commonly and successfully employed.
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PMID:The role of the immune system in the pathogenesis of cancer. 154 19

Bone marrow transplantation is a therapeutic treatment for many life-threatening hematologic disorders, especially leukemia and certain immune deficiency diseases. However, acute graft-versus-host disease is often associated with bone marrow transplantation. In mice, allogeneic GVHD appears to be mediated by both host natural killer cells and donor T cells. In vitro and in vivo experiments demonstrate that treatment with either YN1/1.7 or M17/4.2 mabs is immunomodulatory and inhibits both the mixed lymphocyte reaction and natural killer cell activity. In addition, utilizing an allogeneic model of acute, lethal GVHD with C57B1/6 mice as donors and sublethally irradiated BDF1 mice as recipients, treatment of host mice with anti-LFA-1 alpha (M17/4.2) or anti-MALA-2 (YN1/1.7) mabs at a dose of 10 mg/kg/day for 10 days significantly reduced GVHD and enhanced survival. Mabs to lymphocyte adhesion molecules such as LFA-1 alpha and MALA-2 may provide a useful therapy for the treatment of GVHD.
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PMID:Reduction in the severity of graft-versus-host disease and increased survival in allogenic mice by treatment with monoclonal antibodies to cell adhesion antigens LFA-1 alpha and MALA-2. 165 92

A 7-year-old leukemic girl developed pancytopenia following chemotherapy and was given several transfusions of nonirradiated blood. Within 2 weeks she developed a maculopapular rash, fever, abnormal liver function, diarrhea, and wasting. She became septic and died 6 weeks later. Transfusion-associated graft-versus-host disease (GVHD) was suspected clinically. At autopsy, changes diagnostic of GVHD were present in the skin and liver. The remarkable feature of the case was the histopathology of the thymus, which was morphologically "dysplastic," i.e., minute, lymphoid depleted, devoid of a corticomedullary demarcation, and completely lacking in Hassall's corpuscles. These changes were virtually identical to those seen in the thymus of children with severe combined immunodeficiency disease (SCID). There was no evidence of preexisting immune deficiency. There is compelling experimental evidence that GVHD can produce changes in the thymus that are identical to those of "thymic dysplasia." These observations have led to the hypothesis that immunodeficiency associated with GVHD may stem, in part, from injury to thymic epithelium resulting in defective T cell maturation. As a corollary of this hypothesis, it has been suggested that the pathogenesis of some forms of SCID may involve GVHD-associated injury to the thymus by a maternal allograft acquired in utero. This report further documents thymic pathology in human GVHD and discusses these changes in the light of these ideas.
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PMID:Thymic involution with loss of Hassall's corpuscles mimicking thymic dysplasia in a child with transfusion-associated graft-versus-host disease. 186 63

Lung disease in patients with severe combined immune deficiency (SCID) undergoing bone marrow transplantation (BMT) is most commonly caused by infection. Noninfectious episodes of pulmonary disease following BMT are more frequently encountered in patients with hematologic disorders or malignancy and are probably related to ablation therapy or graft-versus-host disease (GVHD). In contrast, patients with SCID do not receive chemotherapy before an HLA-identical allogeneic BMT and they do not suffer significant GVHD. We report a patient who developed severe lung disease during the period of rapid engraftment following an HLA-identical allogeneic bone marrow transplantation. Lung biopsy showed dense lymphocytic infiltrates in the alveolar septae and no evidence of infection. Following the idea that the acute recruitment of engrafted lymphocytes may have contributed to or caused the pulmonary disease, we have attempted to suppress cellular immunity by administering high-dose methylprednisolone. The patient's lung disease rapidly improved and eventually completely resolved.
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PMID:Lymphocytic pneumonitis following bone marrow transplantation in severe combined immunodeficiency. 204 28


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