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Graft Versus Host Disease

Parotid salivary gland dysfunction in chronic graft-versus-host disease (cGVHD): a longitudinal study in a mouse model

Bone Marrow Transplantation volume 25, pages 1073–1078 (2000)Cite this article

Abstract

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like phenomenon resulting in morbidity and mortality following allogeneic bone marrow transplantation (BMT). Major salivary gland dysfunction and hyposalivation is one of the prevalent manifestations of cGVHD. We have used the B10.D2 to Balb/C cGVHD mice model in order to assess major salivary gland function in cGVHD, evaluating sialometric, sialochemical and histopathological parameters for almost 3 months. As cGVHD is a chronic debilitating disease it is of vast importance to evaluate these parameters on a prolonged longitudinal basis. We observed significant reduction in parotid salivary flow rate and disturbance in the salivary dynamic function in cGVHD mice in comparison to the normal and syngeneic transplanted controls. On days 18, 25, 46, 56 and 88 the mean flow rates of the cGVHD group were 37.4 ± 4.4 μl/30 min, 40.5 ± 4.6 μl/30 min, 32.5 ± 2.3 μl/30 min, 22.2 ± 3.2 μl/30 min and 14.8 ± 3.8 μl/30 min, respectively, values which were lower than those of the syngeneic transplanted controls group by 42% (P < 0.04), 32% (P < 0.03), 44% (P < 0.01), 49% (P < 0.01) and 64% (P < 0.01), respectively. these changes in flow rates were paralleled by changes in the biochemical composition of the saliva. moreover, the reduction in flow rates correlated with the degree of salivary gland destruction observed in the pathological slides. an inverse correlation was observed between the mean parotid salivary flow rate and the degree of fibrosis observed in the histopathological evaluation of the cgvhd mice (P < 0.01). maximal flow rate 34.8 ± 4.6 μl/30 min was observed when no fibrosis was observed while in mice with maximal fibrosis flow rates were minimal. this may point to the pathological mechanism leading to the major salivary gland dysfunction and hyposalivation observed in cgvhd. thus, it may broaden our knowledge and provide the scientific background for designing better therapeutic strategies for this complication. Bone Marrow Transplantation (2000) 25, 1073–1078.

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References

  1. Slavin S, Nagler A . New developments in bone marrow transplantation Curr Opin Oncol 1991 3: 254–271

    Article  CAS  Google Scholar 

  2. O'Reilly RJ . Allogeneic bone marrow transplantation: current status and future directions Blood 1982 62: 941–964

    Google Scholar 

  3. Slavin S (ed) . Bone Marrow And Organ Transplantation: Achievements And Goals Elsevier: Amsterdam 1984

    Google Scholar 

  4. Izutsu KT, Sullivan KM, Schubert MM et al. Disordered salivary immunoglobulin secretion and sodium transport in human disease graft-versus-host disease Transplantation 1983 35: 441–446

    Article  CAS  Google Scholar 

  5. Chaushu S, Chaushu G, Garfinkle AA et al. Salivary immunoglobulins in recipients of bone marrow grafts. II. Transient secretion of donor-derived salivary IgA following major transplantation of T cell-depleted bone marrow Bone Marrow Transplant 1994 14: 925–928

    CAS  PubMed  Google Scholar 

  6. Chaushu S, Chaushu G, Garfinkle AA et al. Salivary immunoglobulins in recipients of bone marrow grafts I. A longitudinal follow-up Bone Marrow Transplant 1994 14: 871–876

    CAS  PubMed  Google Scholar 

  7. Nagler RM, Laufer D, Nagler A . Parotid gland dysfunction in an animal model of chronic graft-versus-host disease Arch Otolaryngol Head Neck Surg 1996 122: 1057–1060

    Article  CAS  Google Scholar 

  8. Nagler R, Laufer D, Nagler A . Parotid gland dysfunction in a murine model of acute graft versus host disease Head Neck 1998 201: 58–62

    Article  Google Scholar 

  9. Nagler R, Marmary Y, Krausz Y et al. Salivary gland dysfunction in human acute and chronic graft versus host disease (GVHD) Bone Marrow Transplant 1996 17: 219–224

    CAS  PubMed  Google Scholar 

  10. Nagler RM, Nagler A . Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease patients: a sialometrical study Bone Marrow Transplant 1999 23: 1007–1111

    Article  CAS  Google Scholar 

  11. Mandel ID . The role of saliva in maintaining oral homeostasis J Am Dent Assoc 1989 119: 298–304

    Article  CAS  Google Scholar 

  12. Fox PC, Van Der Van P, Sonies BC et al. Xerostomia: evaluation of a symptom with increasing significance J Am Dent Assoc 1985 110: 519–525

    Article  CAS  Google Scholar 

  13. Jaffee BD, Claman HN . Chronic graft-vs-host disease (GVHD) as a model for scleroderma. I. Description of model systems Cell Immunol 1983 77: 1–12

    Article  CAS  Google Scholar 

  14. Ben-Aryeh H, Jungerman T, Szargel R et al. Salivary flow-rate and composition in schizophrenic patients on clozapine: subjective reports and laboratory data Biol Psychiatr 1996 39: 946–949

    Article  CAS  Google Scholar 

  15. Ben-Aryeh H, Serouya R, Kantger Y et al. Oral health and salivary composition in diabetic patients J Diab Comp 1993 7: 57–62

    Article  CAS  Google Scholar 

  16. Nagler R, Nagler A . Effects of ionizing irradiation and β-adrenergic stimulation on gene expression in rat submandibular glands Anticancer Res 1996 16: 2749–2756

    CAS  PubMed  Google Scholar 

  17. Nagler RM, Baum BJ, Fox PC . A 2 week pair-fed study of early X-irradiation effects on rat major salivary gland function Arch Oral Biol 1996 41: 713–719

    Article  CAS  Google Scholar 

  18. Nagler RM, Baum J, Fox PC . Acute effects of X-irradiation on the function of rat salivary glands Radiat Res 1993 1036: 42–47

    Article  Google Scholar 

  19. Nagler RM, Baum BJ, Fox PC . Effects of X-irradiation on the function of rat salivary glands at 3 and 40 days Radiat Res 1993 136: 392–396

    Article  CAS  Google Scholar 

  20. Tricot GJK, Zwaan FE, Kauffman RH et al. Extreme potassium loss in a patient with severe graft versus host disease Scan J Hematol 1980 25: 264–267

    Article  CAS  Google Scholar 

  21. Khairaallah M, Spach C, Maitre F, Motta R . Endocrine involvement in minor (non H-2) graft-versus-host reaction in mice: dissociated effect on corticosterone and aldosterone plasma levels Endocrinol 1988 123: 1949–1954

    Article  Google Scholar 

  22. Sale GE, Shulman HM, Schubert MM et al. Oral and ophthalmic pathology of graft-versus-host disease in man: predictive value of lip biopsy Hum Pathol 1981 12: 1022–1030

    Article  CAS  Google Scholar 

  23. Rudo B, Gockerman JP . Oral manifestations of chronic graft-v-host reaction JAMA 1983 249: 504–507

    Article  Google Scholar 

  24. Hiroki A, Nakamura S, Shinohara M, Oka M . Significance of oral examination in chronic graft-versus-host disease J Oral Pathol Med 1994 23: 209–215

    Article  CAS  Google Scholar 

  25. Schubert MM, Sullivan KM, Izutsu KT et al. Oral complications of bone marrow transplantation. In: Peterson DE, Sonis ST (eds) Oral Complications of Cancer Chemotherapy Martinus Nijhoff: The Hague 1983 93–112

    Chapter  Google Scholar 

  26. Marmary Y, Okon E, Katz J, Shiloni E . Effect of interleukin-2 on salivary gland morphology and function in mice Lympho Cyto Res 1994 13: 197–201

    CAS  Google Scholar 

  27. Nagler A, Nagler R, Ackerstein A et al. Major salivary gland dysfunction in patients with hematological malignancies receiving interleukin-2-based immunotherapy post-autologous blood stem cell transplantation Bone Marrow Transplant 1997 20: 575–580

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oral Medicine and Radiology, Hadassah University Hospital, Jerusalem, Israel

    S Levy & Y Marmary

  2. Department of Bone Marrow Transplantation and the Cancer Immunobiology Research Laboratory, Hadassah University Hospital, Jerusalem, Israel

    A Nagler

  3. Department of Pathology, Hadassah University Hospital, Jerusalem, Israel

    S Okon

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  1. S Levy
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Levy, S., Nagler, A., Okon, S. et al. Parotid salivary gland dysfunction in chronic graft-versus-host disease (cGVHD): a longitudinal study in a mouse model. Bone Marrow Transplant 25, 1073–1078 (2000). https://doi.org/10.1038/sj.bmt.1702383

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