Primary immunodeficiencies (PID) are frequently complicated by non-Hodgkin’s lymphomas (NHLs). We present three cases with compound heterozygous mutations in DOCK8, NBAS and PGM3 transcripts. All had an extraordinary disease course.
We compared DOCK8, NBAS and PGM3 versus IgG-RNA expression within plasma cell malignancy.
Case 1. A 19-year-old woman with compound heterozygous DOCK8 mutations, severe infections and impaired vaccination response developed undefined necrotic inflammations in liver and kidneys, after spontaneous involution she developed a large B-cell NHL, stage IV (EBV negative). Treatment was successful with chemo/radiotherapy. Three years later she developed refractory Hodgkin’s lymphoma. Bone marrow transplantation (BMT) was complicated by lethal GVH reaction.
Case 2. A 45-year-old woman with achromatopsia, dwarfism, hypothyroidism and hypogammaglobinemia due to a mutation in NBAS developed stage IV, pelvic marginal zone NHL. She had longstanding oligoclonal CD8+ T cell lymphocytosis and was EBV-DNA positive. Treatment was successful with chemotherapy/rituximab.
Case 3. A 37-year-old woman with hypogammaglobulinemia, B- and T-lymphopenia, granulopenia and hyper-IgE due to heterozygous mutations in PGM3 presented with gastrointestinal large cell diffuse B-cell NHL of the gut. She was successfully treated with BMT after chemotherapy/rituximab. No EBV infection was detected.
High expression of DOCK8, NBAS, and PGM3 correlated with high IgG production in myeloma samples (NCBI GEO dataset GSE19784).
DOCK8 and PGM3 mutation frequently develop NHL, we also present a NBAS patient with NHL and suggest that impairment of these genes may affect the IgG synthesis.