Summary:Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention. Keywords: autoimmune thrombocytopenia; BMT; severe combined immunodeficiency Severe combined immunodeficiency (SCID) is a syndrome describing children with profound cellular and humoral immune dysfunction attributable to different causes such as enzyme deficiencies (ADA, PNP), 1,2 T cell defects, defective HLA expression, as well as the more common ␥c deficiency. 3 For these patients, with the exception of ADA deficiency, bone marrow transplantation (BMT) is the therapy of choice. 4,5 The time taken for engraftment of the marrow cells and immune reconstitution varies depending on multiple factors. These include: (a) the use of T cell depleted 6-8 vs unfractionated bone marrow cells; 9,10 (b) pre-transplant conditioning; (c) the presence or absence of graft-versushost disease (GVHD) and its treatment; 11 (d) concomitant infections; and (e) the general status of the patient. 12 During this early post-transplant period, the immune imbalance observed as the donor immune system emerges, modified by the host, results in well described symptom complexes such as GVHD. 11,[13][14][15][16] This underlying immune dysregulation may also result in autoimmune cytopenias. 12,17 We report two cases of severe AITP following a haploidentical, T cell-depleted allogeneic BMT for SCID. Case report Patient AA girl presented with recurrent respiratory infections and persistent diarrhea and was diagnosed with T − B + SCID with normal adenosine deaminase (ADA) and purine nucleophosphorylase (PNP) levels at 3 months of age. Her hematological and immunological profile at presentation were: hemoglobulin (Hb) 11.8 g/dl, white cell count (WCC) 4.6 × 10 9 /l, platelet count (plat) 225 × 10 9 /l, Ig G/A/M of 1.7, Ͻ 0.1, 0.3 g/l, respectively, CD3 Ͻ0.02 (normal 0.9-1.6), CD4 Ͻ0.02 (normal 0.7-1.2), CD8 Ͻ0.02 (0.3-9.7), CD19 1.74 (0.16-0.36) and NK cells 0.39 (0.13-0.35) × 10 9 /l. Response to mitogen was not performed due to the almost absent number of T cells. She underwent a T cell-depleted (soybean lectin sheep E-rosetting), haploidentical BMT without conditioning from her father at 4 months of age. Engraftment was documented on day +21 post-transplant by fluorescent in situ hybridization (FISH) studies for XY cells and the post-transplantation course was complicated by respiratory failure, acute renal failure and graft-versus-host disease (GVHD) involving skin and gastrointestinal tract...
X‐linked severe combined immunodeficiency (XSCID) is a lethal disease resulting in death in infancy. In many instances, haploidentical bone marrow transplantation (BMT) offers reconstitution of T‐cell immunity alone, with residual hypogammaglobulinaemia. The exact nature of B‐cell dysfunction in these patients is unclear, although differentiation arrest of the B cells is a potential explanation. To ascertain the differentiation status of peripheral blood B lymphocytes from XSCID patients after BMT, the surface expression of CD19, CD10, CD34, CD5, serum immunoglogulin (sIg)M, sIgD, sIgG and CD27 on these B cells was investigated using three‐colour flow cytometry. CD27 is a marker of memory B cells. Populations of CD19+IgM−D− B cells, CD19+IgM‐only, CD19+IgG+CD27+ and CD19+IgM+ CD27+ B cells were found to be diminished in the XSCID patients after BMT with persistent hypogammaglobulinaemia, compared with both post‐BMT patients with B‐cell function and age‐matched normal controls. This indicated the lack of CD19+IgM−D− B cells, which represent Ig isotype‐switched B cells, as well as CD19+IgM‐only and CD19+IgG+CD27+ or CD19+IgM+CD27+ memory B‐cell populations. Interaction between CD27 and its ligand CD70 has been shown to induce IgG and IgM production by CD27+ B cells. Therefore, the lack of CD27/70 interaction is a probable explanation for the hypogammaglobulinaemia in these patients after BMT.
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