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Development of multiple monoclonal serum immunoglobulins (multiclonal gammopathy) following both HLA-identical unfractionated and T cell-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency

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Abstract

We have identified five patients with severe combined immunodeficiency (SCID) who developed multiple monoclonal serum immunoglobulin components (multiclonal gammopathy) following bone marrow transplantation. Four patients received haploidentical bone marrow stem cells depleted of T cells and other mature marrow cells by soy lectin agglutination and/or sheep erythrocyte rosetting. One patient received unfractionated HLA-identical bone marrow. Twenty-one distinct paraproteins were detected: 14 IgG, 5 IgM, and 2 IgA, all containing either kappa or lambda light chains. In the haploidentical stemcell recipients, these monoclonal immunoglobulins appeared immediately prior to, or concomitant with, a rise in T-cell numbers and function. Resolution or diminution of this multiclonal gammopathy occurred as T-cell function was established. Posttransplant karyotypic analyses revealed PHA-stimulated T cells to be of donor origin in all patients. Karyotyping of B-cell lines posttransplantation revealed them to be 100% donor in the patient receiving unfractionated HLA-identical marrow and 100% host (1/4), 100% donor (1/4), mixed (1/4), or not tested (1/4) in the patients receiving haploidentical marrow stem cells. There was no evidence of Epstein-Barr virus (EBV) infection in any of the patients. All patients are currently alive and well. Immunoglobulin synthesis is normal in the patient who received the HLA-identical marrow but remains below normal in the four patients who received T cell-depleted haploidentical stem cells. The posttransplantation development of monoclonal immunoglobulins in the absence of EBV infection did not adversely affect the outcome of either HLA-identical marrow or haploidentical stem-cell grafting. The development of these monoclonal components posttransplantation in SCID patients is a more common phenomenon than previously recognized (26% of 31 patients we have evaluated). The onset and resolution of multiclonal gammopathy in this patient population may have implications for the pathogenesis of other clonal B-cell and plasma disorders.

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Authors and Affiliations

  1. Department of Pediatries, Division of Allergy and Immunology, and Department of Microbiology and Immunology and Division of Hematology/Oncology, Department of Medicine, Protein Laboratory and Center for the Study of Aging and Human Development, Duke University Medical Center, and Geriatric Research Education and Clinical Center, Veterans Administration Medical Center, Durham, North Carolina

    E. F. Kent Jr., J. Crawford, H. J. Cohen & R. H. Buckley

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  1. E. F. Kent Jr.
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  2. J. Crawford
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  3. H. J. Cohen
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  4. R. H. Buckley
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Kent, E.F., Crawford, J., Cohen, H.J. et al. Development of multiple monoclonal serum immunoglobulins (multiclonal gammopathy) following both HLA-identical unfractionated and T cell-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency. J Clin Immunol 10, 106–114 (1990). https://doi.org/10.1007/BF00918192

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