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Title: Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

Abstract

The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunitymore » in GVHD and graft rejection in dogs is postulated.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
5011989
Resource Type:
Journal Article
Resource Relation:
Journal Name: Transplantation; (United States); Journal Volume: 6
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BONE MARROW; TRANSPLANTS; DOGS; GRAFT-HOST REACTION; BIOLOGICAL MODELS; BIOLOGICAL RADIATION EFFECTS; DOSE-RESPONSE RELATIONSHIPS; GAMMA RADIATION; IMMUNITY; IMMUNOGLOBULINS; TIME DEPENDENCE; WHOLE-BODY IRRADIATION; ANIMAL TISSUES; ANIMALS; BIOLOGICAL EFFECTS; BODY; ELECTROMAGNETIC RADIATION; EXTERNAL IRRADIATION; GLOBULINS; HEMATOPOIETIC SYSTEM; IONIZING RADIATIONS; IRRADIATION; MAMMALS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; RADIATION EFFECTS; RADIATIONS; TISSUES; VERTEBRATES; 560152* - Radiation Effects on Animals- Animals

Citation Formats

Vriesendorp, H.M., Halliwell, R.E., Johnson, P.M., Fey, T.A., and McDonough, C.M. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation. United States: N. p., 1985. Web. doi:10.1097/00007890-198506000-00002.
Vriesendorp, H.M., Halliwell, R.E., Johnson, P.M., Fey, T.A., & McDonough, C.M. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation. United States. doi:10.1097/00007890-198506000-00002.
Vriesendorp, H.M., Halliwell, R.E., Johnson, P.M., Fey, T.A., and McDonough, C.M. Sat . "Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation". United States. doi:10.1097/00007890-198506000-00002.
@article{osti_5011989,
title = {Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation},
author = {Vriesendorp, H.M. and Halliwell, R.E. and Johnson, P.M. and Fey, T.A. and McDonough, C.M.},
abstractNote = {The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.},
doi = {10.1097/00007890-198506000-00002},
journal = {Transplantation; (United States)},
number = ,
volume = 6,
place = {United States},
year = {Sat Jun 01 00:00:00 EDT 1985},
month = {Sat Jun 01 00:00:00 EDT 1985}
}
  • The restoration of immune functions was followed in dogs for 101 days after fractionated total body irradiation and autologous transfusion of peripheral blood leukocytes (PBL) or bone marrow (BM) cells. Median numbers of 0.9 X 10(5) granulocyte-macrophage progenitor cells per kilogram of body weight were transferred in either group of recipients. The following parameters recovered more rapidly in PBL recipients as opposed to BM recipients: total blood lymphocyte, T- and B-cell counts, serum levels of immunoglobulins IgM and IgA, in vitro blastogenic responses after stimulation with concanavalin A and pokeweed mitogen, and in vitro plasma cell formation after polyclonal B-cellmore » activation with pokeweed mitogen with or without lipopolysaccharide. No major differences were noted for the restoration of serum IgG levels. Circulating lymphocyte and T-cell numbers remained subnormal for more than three months in both groups, whereas B-cell numbers and serum levels of IgA continued to be depressed in BM recipients only. Thus, autologous PBL restored immune functions more rapidly than did BM. Transplantation of PBL, alone or in addition to autologous BM, might also shorten the period of immunodeficiency after cytoreduction in a variety of malignancies in man.« less
  • One hundred fifty-three dogs were given 6.1-21.3 Gy total body irradiation at 0.02-0.2 Gy/minute delivered from two opposing cobalt sources followed by allogeneic (131 dogs) or autologous (22 dogs) marrow grafts and observed for 6-127 (median 33) months. The incidence of malignant tumors in radiation chimeras was compared to that in 242 untreated dogs observed for 6-188 (median 81) months. Thirteen malignancies were observed in 11 radiation chimeras. Fifty-four malignancies were seen in 44 control dogs. On the basis of time-dependent Cox regression analysis, radiation chimeras had an estimated relative risk of developing a malignancy that was 5-fold higher thanmore » in control dogs (p < 0.001). No tumor has yet been observed in a group of 15 chimeras conditioned by cyclophosphamide or dimethyl busulfan and followed for 6-97 (median 24) months. The increased risk of cancer among canine radiation chimeras suggests that high-dose total body irradiation may increase the risk of developing a malignancy and should be avoided whenever possible in the conditioning for marrow transplantation of human patients with nonmalignant diseases.« less
  • We evaluated the effects of 16,16-dimethyl prostaglandin E2 (dm-PGE2), with and without syngeneic bone marrow transplantation (BMT) on the survival and hematopoietic recovery of mice given 14-20 Gy total body irradiation (TBI). Survival of mice given combined dm-PGE2 and BMT was improved significantly over that of mice given either treatment alone. The 30-day survival after 14, 15, 16 or 18 Gy TBI for combined treatment was 97, 90, 20 or 10 percent, respectively. The corresponding 30-day survival rates for mice given BMT alone were 69, 60, 7 or 0 percent, respectively. For dm-PGE2 alone, 30-day survival was 63, 20, 10more » or 0 percent, respectively. Deaths in both dm-PGE2 treated groups generally occurred after day 10 whereas deaths in the BMT group occurred before day 10. All irradiated controls were dead on or before day 10; after larger doses, deaths clustered around day 5. After 20 Gy TBI, all mice in all groups were dead by day 7. Studies of white blood cell recovery 1-9 days after 14 Gy TBI showed improvement with BMT, whereas dm-PGE2 did not enhance recovery. Nucleated cells per humerus, spleen weight, and spleen iron uptake (erythropoiesis) were also improved by BMT but not dm-PGE2.« less
  • The recovery of fibroblastic colony-forming units (CFU-F) in murine bone marrow hemopoietic stroma was studied during eighteen months after 9 Gy lethal total-body irradiation and reconstitution with syngeneic bone marrow cells. After an initial depletion, CFU-F numbers increased from 10% of normal values at three months to 40% at 18 months after treatment, irrespective of graft size and presence of CFU-F in the graft. Fourteen months after treatment 35% of all CFU-F present in the recipients bone marrow was donor-derived independent of graft size. When mice were treated with high-dose lipopolysaccharide-W three months after irradiation and bone marrow transplantation, CFU-Fmore » numbers decreased to hardly detectable levels within one day, and then recovered to normal numbers four weeks later--whereas radiation control mice still had low CFU-F numbers. These data suggest that after lethal total-body irradiation the stroma still contained viable fibroblastic cells that had lost their in vitro colony-forming capacity as a result of radiation damage. In consequence there was no need for replacement of these fibroblastic cells by donor-derived or host-derived CFU-F. Only depletion of CFU-F from the bone marrow, as was induced with lipopolysaccharide, stimulated repopulation of the stroma with colony-forming fibroblastic cells.« less