Skip to main content

Advertisement

SpringerLink
Log in

Appearance of multiple benign paraproteins during early engraftment of soy lectin T cell-depleted haploidentical bone marrow cells in severe combined immunodeficiency

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Recent advances in the prevention of graft-versus-host disease through postthymic T-cell depletion have allowed the use of haploidentical bone marrow cells for immunologic reconstitution of severe combined immunodeficiency disease. We report a male infant with severe combined immunodeficiency (with normal adenosine deaminase) who developed two IgG kappa and one IgA lambda paraproteins 7 weeks following the administration of 1.4×109 maternal bone marrow cells depleted of postthymic T cells by soy lectin agglutination and sheep erythrocyte rosetting. Serum IgG rose from 128 to 820 mg/dl, and IgA from 0 to 2400 mg/dl, peaking at 10 weeks postgrafting. By 14 weeks posttransplantation T-cell numbers and function had risen to normal (all dividing T cells had the donor karyotype) and paraprotein concentrations began to decline. These observations strongly suggest that the later-appearing T cells regulated the B-cell clones from which the paraproteins were derived. Failure of such function to appear could account for the increased incidence of B-cell lymphomas in severe combined immunodeficiency.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bortin MM, Rimm AA: Severe combined immunodeficiency disease. Characterization of the disease and results of transplantation. JAMA 238:591–600, 1977

    Google Scholar 

  2. Reisner Y,et al.: Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 61:341–348, 1983

    Google Scholar 

  3. Friedrich W, Vetter U, Heymer B,et al.: Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T cell depleted bone marrow. Lancet 1:761–764, 1984

    Google Scholar 

  4. Fischer A, Durandy A, Vilmer E,et al.: Mismatched bone marrow transplantation for severe combined immunodeficiency (SCID) using E rosette fractionation and cyclosporin A.In Progress in Immunodeficiency Research and Therapy I, C Griscelli, J Vossen (eds). New York, Elsevier Science, 1984, pp 409–416

    Google Scholar 

  5. Reinherz E, Geha R, Rappaport J,et al.: Reconstitution after transplantation with T lymphocyte depleted HLA haplotype mismatched bone marrow for severe combined immunodeficiency. Proc Natl Acad Sci 79:6047–6051, 1982

    Google Scholar 

  6. DeKoning J, Van Bekkum DW, Dicke HA, Dooren LH, Van Rood JJ, Radl J: Transplantation of bone marrow cells and fetal thymus in an infant with lymphopenic immunological deficiency. Lancet 1:1223–1227, 1969

    Google Scholar 

  7. Buckley RH, Dees SC, O'Fallon WM: Serum immunoglobulins. I. Levels in normal children and in uncomplicated childhood allergy. Pediatrics 41:600–611, 1968

    Google Scholar 

  8. Buckley RH, Fiscus SA: Serum IgD and IgE concentrations in immunodeficiency. J Clin Invest 55:157–165, 1975

    Google Scholar 

  9. Buckley RH, Dees SC: Serum immunoglobulins. III. Abnormalities associated with chronic urticaria in children. J Allerg 40:294–303, 1968

    Google Scholar 

  10. Schiff RI, Buckley RH, Gilbertsen RB, Metzgar RS: Membrane receptors andin vitro lymphocyte responsiveness in immunodeficiency. J Immunol 112:376–385, 1974

    Google Scholar 

  11. Haynes BF: Human T lymphocyte antigens as defined by monoclonal antibodies. Immunol Rev 57:127–161, 1981

    Google Scholar 

  12. Koren HS, Amos DB, Buckley RH: Natural killing in immunodeficient patients. J Immunol 120:796–799, 1978

    Google Scholar 

  13. Spector BD, Perry GS, Kersey JH: Genetically determined immunodeficiency diseases (GDID) and malignancy: Report from the Immunodeficiency-Cancer Registry. Clin Immunol Immunopathol 11:12–29, 1978

    Google Scholar 

  14. Perussia B, Starr S, Abraham S, Fanning V, Trinchieri G: Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor function. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol 130:2133–2141, 1983

    Google Scholar 

  15. Phillips JH, Babcock GF: NKP-15: a monoclonal antibody reactive against purified human natural killer cells and granulocytes. Immunol Lett 6:143–149, 1983

    Google Scholar 

  16. Gelfand EW, Baumal R, Huber J, Crookston MC, Shumak KH: Polyclonal gammopathy and lymphoproliferation after transfer factor in severe combined immunodeficiency disease. N Engl J Med 289:1385–1389, 1978

    Google Scholar 

  17. Groshong T, Horowitz S, Lovchik J, David A, Hong R: Chronic cytomegalovirus infection, immunodeficieny, and monoclonal gammopathy—antigen-driven malignancy? J Pediat 88:217–223, 1976

    Google Scholar 

  18. Shirley LR, Buckley RH, Borowitz MJ, Welt SI, Kostyu DD: Monoclonal immunoglobulin-secreting lymphoma in a patient with severe combined immunodeficiency disease. Clin Exp Immunol 48:666–674, 1982

    Google Scholar 

  19. Borzy MS, Hong R, Horowitz SD,et al.: Fatal lymphoma after transplantation of cultured thymus in children with combined immunodeficiency disease. N Engl J Med 301:565–568, 1979

    Google Scholar 

  20. Reece ER, Gartner JG, Seemayer TA, Joncas JH, Pagano JS: Epstein-Barr virus in a malignant lymphoproliferative disorder of B cells occurring after thymic epithelial transplantation for combined immunodeficiency. Cancer Res 41:4243–4247, 1981

    Google Scholar 

  21. Peter HH, Friedrich W, Dopfer R,et al.: NK cell function in severe combined immunodeficiency (SCID): Evidence of a common T and NK cell defect in some but not all SCID patients. J Immunol 131:2332–2339, 1983

    Google Scholar 

  22. Shearer WT, Ritz J, Finegold MJ, Guerra IC,et al.: Epstein-Barr virus-associated B cell proliferations of diverse clonal origins after bone marrow transplantation in a 12 year old patient with severe combined immunodeficiency. N Engl J Med 312:1151–1159, 1985

    Google Scholar 

  23. Harboe M, Pandee H, Brandtzaeg P, Tveter KJ, Hjort PF: Synthesis of donor type gamma G globulin following thymus transplantation in hypogammaglobulinemia with severe lymphopenia. Scand J Hematol 3-351–374, 1966

    Google Scholar 

  24. De Fazio SR, Criswell BS, Kimzey SL, South MA, Montgomery JR: A paraprotein in severe combined immunodeficiency disease detected by immunoelectrophoretic analysis of plasma. Clin Exp Immunol 19:563–570, 1975

    Google Scholar 

  25. Radl J, Dooren LJ, Morell A, Skvaril F, Vossen JM, Uittenbogaart CH: Immunoglobulins and transient paraproteins in sera of patients with the Wiskott-Aldrich syndrome: A follow-up study. Clin Exp Immunol 25:256–263, 1976

    Google Scholar 

  26. Schaller J, Ching T-C, Williams CPS, Davis SD, Lagunoff D, Wedgwood RJ: Hypergammaglobulinemia, antibody deficiency, autoimmune hemolytic anemia, and nephritis in an infant with a familial lymphopenic immune defect. Lancet 2:825–829, 1966

    Google Scholar 

  27. Becroft DMO, Douglas R: Thymic alymphoplasia, monoclonal gammopathy, and Pneumocystis carinii pneumonia in an infant. Arch Dis Child 43:444–450, 1968

    Google Scholar 

  28. Geha RS, Schneeberger E, Gatien J, Rosen FS, Merler E: Synthesis of an M component by circulating B lymphocytes in severe combined immunodeficiency. N Engl J Med 290:726–728, 1974

    Google Scholar 

  29. Scalzo AA, Anders EM: Influenza viruses as lymphocyte mitogens. I. B cell mitogenesis by influenza A viruses of the H2 and H6 subtypes is controlled by the I-E/C subregion of the major histocompatibility complex. J Immunol 134:757–760, 1985

    Google Scholar 

  30. Penn I: Malignant lymphomas in organ transplant recipients. Transplant Proc 13:736–738, 1981

    Google Scholar 

  31. Cleary ML, Sklar J: Lymphoproliferative disorders in cardiac transplant recipients are multiclonal lymphomas. Lancet 2:489–493, 1984

    Google Scholar 

  32. Frizzera G, Hanto DW, Gajl-Peczalska KJ,et al.: Polymorphic diffuse B cell hyperplasias and lymphomas in renal transplant recipients. Cancer Res 41:4262–4279, 1981

    Google Scholar 

  33. Hanto DW, Frizzera G, Purtilo DT,et al.: Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Cancer Res 41:4253–4261, 1981

    Google Scholar 

  34. Starzl TE, Nalesnik MA, Porter KA,et al.: Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1:583–587, 1984

    Google Scholar 

  35. Trigg ME, Billing R, Sondel PM, Exten R, Hong R, Bozdech MJ, Horowitz SD, Finley JL, Moen R, Longo W, Erickson C, Peterson A: Clinical trial depleting T lymphocytes from donor marrow for matched and mismatched allogeneic bone marrow transplants. Cancer Treat Rep 69:377–386, 1985

    Google Scholar 

  36. Martin PJ, Shulman HM, Schubach WH,et al.: Fatal Epstein-Barr virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T cell antibody. Ann Intern Med 101:310–315, 1984

    Google Scholar 

  37. DeVoe PW, Buckley RH, Shirley LR, Darby CP, Ward FE, Mickey GH, Raab-Traub N, Vandenbark GR: Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections. Clin Immunol Immunopathol 34-48–59, 1985

    Google Scholar 

  38. Sindel LJ, Buckley RH, Schiff SE, Ward FE, Mickey GH, Huang AT, Naspitz C, Koren H: Severe combined immunodeficiency with natural killer cell predominance: Abrogation of graft-versus-host disease and immunologic reconstitution with HLA identical bone marrow cells. J Allerg Clin Immunol 73:829–836, 1984

    Google Scholar 

  39. Buckley RH, Schiff SE, Sampson HA, Schiff RI, Markert ML, Knutsen AP, Hershfield MS, Huang AT, Mickey GH, Ward FE: Development of immunity in human severe primary T cell deficiency following haploidentical bone marrow stem cell transplantation. J Immunol 136:(April), 1986

Download references

Author information

Authors and Affiliations

  1. Departments of Pediatrics and Microbiology and Immunology, Duke University Medical Center, 27710, Durham, North Carolina

    Patricia Ghory, Sherrie Schiff & Rebecca Buckley

Authors
  1. Patricia Ghory
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sherrie Schiff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebecca Buckley
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghory, P., Schiff, S. & Buckley, R. Appearance of multiple benign paraproteins during early engraftment of soy lectin T cell-depleted haploidentical bone marrow cells in severe combined immunodeficiency. J Clin Immunol 6, 161–169 (1986). https://doi.org/10.1007/BF00918749

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00918749

Key words

Search

Navigation