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

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 X 10(9) 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.

Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes

“…Serum IgG prior to transplantation was in most cases maternal or from intravenous immunoglobulin, but paraproteins were present in some. One of the IL-7Rα-deficient patients had both IgG and IgA paraproteins prior to transplantation, as has been noted previously in SCID(51–53). At their latest evaluation, 62 patients have normal serum IgA, 98 normal IgM and 52 have isohemagglutinins appropriate for host red blood cell type.…”

Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency

“…A similar process of donor T cells activating host B cells was previously described in other patients with SCID from our institution who had multiple monoclonal serum immunoglobulins (multiclonal gammopathy) after T celldepleted, haploidentical, bone marrow stem cell transplantation. 19,20 However, the possibility also exists that the B cells were transplacentally acquired maternal B cells, as has been noted previously. 21 In summary, we present 2 cases of transplacental T-cell engraftment leading to different clinical manifestations in patients with SCID.…”

Autoimmune hemolytic anemia in patients with SCID after T cell-depleted BM and PBSC transplantation

“…10,11 During the reconstitution of the immune system, after T cell-depleted transplants for SCID, multiple immune defects are present, including decreased cytokine production (IL-6, IL-4), lack of specific antibody production, and deficits in T cell/B cell cooperation. 12 Kent et al, 11 Ghory et al 13 and Hammarstrom et al 14 described the development of multiple monoclonal serum immunoglobulins 48-63 days following T celldepleted transplants in SCID patients, and their disappearance after reconstitution of T cell immunity. 11,13 Similarly, Chen et al 3 reported paraproteins in six of nine patients with post-transplant AIHA, which is more common than in other post-transplant patients.…”

“…12 Kent et al, 11 Ghory et al 13 and Hammarstrom et al 14 described the development of multiple monoclonal serum immunoglobulins 48-63 days following T celldepleted transplants in SCID patients, and their disappearance after reconstitution of T cell immunity. 11,13 Similarly, Chen et al 3 reported paraproteins in six of nine patients with post-transplant AIHA, which is more common than in other post-transplant patients. 14 Due to the retrospective nature of our study we do not have information on immunoelectrophoresis in our patients.…”