Here we describe a 10-year-old girl with combined immunodeficiency presenting as recurring chest infections, lung disease and herpetic skin infections. The patient experienced two hematopoietic stem ...cell transplantations and despite full chimerism, she developed bone marrow aplasia due to adenovirus infection and died at post-transplant day 86. Immunologic investigation revealed low numbers of TRECs/KRECs, a severe reduction of memory B cells, absence of isohemagglutinins, and low IgG levels. Whole exome sequencing (WES) identified a novel heterozygous mutation in RAC2(c.275A > C, p.N92 T). Flow cytometric investigation of neutrophil migration demonstrated an absence of chemotaxis to fMLP. Cell lines transfected with RAC2 N92 T displayed characteristics of active GTP-bound RAC2 including enhanced NADPH oxidase-derived superoxide production both at rest and in response to PMA.
Our findings broaden the clinical picture of RAC2 dysfunction, showing that some individuals can present with a combined immunodeficiency later in childhood rather than a congenital neutrophil disease.
•We report a new case of heterozygous RAC2 deficiency, with the clinical presentation of recurrent respiratory infections, lung disease and susceptibility to varicella and herpetic infections.•Our report expands the phenotypic spectrum of RAC2 deficiency•Dominant activating mutations in RAC2 gene can lead to presentations of combined immunodeficiency where both myeloid and lymphoid lineages are affected
Neuroblastoma is an example of a difficult-to-treat tumor with high incidence of relapse. DNA vaccination could be applied as a relapse prophylactic option for patients with high-risk neuroblastoma. ...Its efficacy depends directly on a target antigen of choice and a delivery method. Three neuroblastoma-associated antigens (tyrosine hydroxylase, Survivin, PHOX2B) and two delivery methods were investigated. Our data suggest that antigen PHOX2B is a more immunogenic target that induces cellular immune response and tumor regression more effectively than tyrosine hydroxylase and Survivin. Immunogenicity testing revealed that the delivery of DNA vaccine by
Salmonella enterica
was accompanied by a stronger immune response (cytotoxicity and IFNγ production) than that by DNA–polyethylenimine conjugate. Nevertheless, intramuscular immunization with PEI led to higher decrease of tumor volume compared to that after oral gavage with Salmonella vaccine.
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder, characterized by spontaneous chromosomal instability with predisposition to immunodeficiency and cancer. We present a repeated ...NBS in two sons from one woman after two marriages. We describe the clinical data, cytogenetic, and molecular findings of a prenatally diagnosed fetus, and his brothers with NBS. The first patient developed peripheral T-cell lymphoma at the age of 16 years and died 5 months after the protocol start. The diagnosis of NBS was established after his death. The second patient was born after the fifth pregnancy, third delivery in the second marriage; he developed cortical T-cell leukemia at the age of 3 years, received hematopoietic stem cells transplantation (HSCT) and he is alive now. In a year after repeated NBS case in this family, mother became pregnant again and the mutation was detected in the male fetus after the prenatal diagnosis; the pregnancy was aborted. At the age of 41 years, mother's seventh pregnancy finished by miscarriage. In three months, she was pregnant again, only one mutation in NBN gene was detected during the prenatal diagnostics in the female fetus; healthy female was born at term. To our knowledge, this is the first time to describe the repeated cases of two patients born with Nijmegen breakage syndrome from one mother and two different fathers. This case highlights the value of checking NBN carrier in Belarusian families during genetic counselling.
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