PMC7474360_01
Radiology at age 43. (a) Chest CT scan with diffuse consolidations, bronchiectasis, and cysts. (b) MRI brain showing bilateral areas of acute infarction and left frontal encephalomalacia from prior insult.
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He also developed progressive respiratory disease (Figure 2(a)) associated with recurrent pneumonia (1-2 episodes per year). MRI of the brain revealed bilateral areas of acute infarction (Figure 2(b)).Additional evaluation failed to identify a primary thrombus.
NK cell cytotoxicity at age 43. Peripheral blood mononuclear cells (PBMCs) from healthy controls or the patient were used as effector cells and were incubated with target cells. (a) Target cells were the K562 monocytic cell line lacking MHC class I. Spontaneous cytotoxicity against these target cells was measured following a 4-hour stimulation +- IL-2. In the absence of IL-2, to lyse 10% of target cells, the patient sample required 25 NK cells per one target cell (25 : 1, NK: target cell ratio). Comparatively, the control required 19 NK cells per one target cell (19 : 1). In the presence of IL-2, the patient sample required 11 NK cells per one target cell (11 : 1) and the control required 9 NK cells per one target cell (9 : 1). (b) Target cells were human lymphoblast-like Raji B cells that express MHC class I CD19 and CD20. Antibody-dependent NK cell cytotoxicity against these target cells was measured following a 4-hour stimulation +- rituximab. No cytotoxicity was observed in the absence of rituximab. In the presence of rituximab, to lyse 5% of target cells, the patient sample required 97 NK cells per one target cell (97 : 1), whereas the control required 16 NK cells per one target cell (16 : 1). This test was performed in a CLIA-certified laboratory.
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NK cell counts (Table 1). NK cell cytotoxicity assays revealed normal spontaneous cytotoxicity but decreased antibody-dependent cytotoxicity (Figure 3).
Flow cytometry at age 43. Isotype staining is shaded in gray. SAP staining is shown in color: red in CD3+CD8+ T cells and blue in CD3-CD56+ NK cells. A healthy control is shown for reference. This figure is representative of repeated tests on two separate instances as performed in a CLIA-certified laboratory.
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By flow cytometry, we found no SAP expression in CD3+CD8+ T cells and CD3-CD56+ NK cells (Figure 4).
Family history with SH2D1A genotype. A full deletion of SH2D1A was detected using a commercial immunodeficiency panel (https://www.invitae.com/en/physician/tests/08100/) in the patient and his mother, while his half brother did not have the deletion. The arrow demarcates the case report patient.
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The patient's mother was a carrier of the same deletion, while his half brother did not have the deletion (Figure 5).
Bone marrow biopsy at age 43. There are large atypical cells on H&E, with a typical staining pattern for classical Hodgkin lymphoma. The neoplastic cells were positive for CD15, CD30, PAX5, and MUM1, while CD20 was negative.
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Hodgkin Lymphoma (Figure 6). He declined chemotherapy and died a few days after diagnosis.