Abstract

Primary Immunodeficiencies (PNO) are a group of about 300 genetic disorders which result from the absence or dysfunction of the major components of the immune system. Among them an important subgroup constitute deficiencies associated with defects in DNA double strand breaks (DSBs) recognition and repair. These are primarily radiation-sensitive severe combined immune deficiencies (SCIDs) and combined immune deficiencies (CIDs) associated with genetic defects in the DNA-repair genes, which encode proteins necessary for T-cell and B cell maturation/differentiation. Due to increased risk of developing malignant neoplasms, mainly from hematopoietic origin, and over-reaction to standard anticancer radiotherapy and chemotherapy, treatment of these patients is a real challenge for clinicians. Clinical and laboratory manifestations, which may indicate increased radiosensitivity include: microcephaly, telangiectasias, lymphopenia, and translocation of chromosomes 7 and 14 in karyotype. A basic test showing increased radiosensitivity of lymphoblastoid cells lines or skin fibroblasts is percentage evaluation of their survival after exposition to ionizing radiation. Treatment of patients with impaired DNA repair depends on the clinical picture, immunological findings and type of immunodeficiency. Patients with SCID require immediate hematopoietic stem cell transplantation (HSCT) using reduced intensity conditioning (RIC). In patients with CID, standard treatment regimens require modification and/or avoidance of radiotherapy and some radiomimetic agents.

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