EBV-Related Hodgkin Lymphoma in an ICF2 Patient: Is EBV Susceptibility a Hallmark of This ICF Subtype?

Progressive Immunodeficiency with Gradual Depletion of B and CD4+ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2)

“…In vivo production of antibodies has been evaluated only in case of three previously reported patients [18,19,20] who all—similar to our patients—presented no or inadequate responses to vaccinations. Low B cell counts have been so far reported for 11 out of 27 patients for whom data are available (i.e., 41%) [9,13,18,19,20,21,22,23] including the here reported patient with hypogammaglobulinemia. Another rarely evaluated, though common abnormality among previously reported ICF2 patients, which we confirmed in our patients, is the substantially reduced CD27 + memory B cell count.…”

“…Here we detected adequate T cell responses to mitogens in all three reported patients. NK cell counts or function had been so far evaluated in 20 patients and only eight of them [3,13,18,19,21,22] including the here presented patients, displayed defects (i.e., 40%).…”

“…For most of them for whom data are available, T cell counts have been reported to be normal. Enhanced percentages of CD8 + T cells appear to be relatively common and are reported for eight among 23 patients for whom data are available (35%) [9,13,18,19,20,21,22]. Increased percentages of CD8 + T cell counts appear in most cases to be the consequence of increased absolute counts of CD8 + T cells in the absence of a relevant CD4 + T cell reduction.…”

Case Report: Primary Immunodeficiencies, Massive EBV+ T-Cell Lympoproliferation Leading to the Diagnosis of ICF2 Syndrome

“…These are usually divided in reactive proliferations (including reactive lesions with no malignant potential like infectious mononucleosis and reactive lesions with varied malignant potential), B cell proliferations (including Hodgkin lymphoma and plasma cell neoplasms), T/natural killer (NK)-cell proliferations and immunodeficiency-related lymphoid proliferations. Combined T-cell and B-cell immunodeficiencies account for about two thirds of PIDs associated with EBV-driven lymphoproliferative disorders ( 4 ).…”

“…There are several primary immunodeficiencies in which EBV+ B-cell LPDs are an important feature, but very few germline mutations have been associated to documented EBV+ T/NK-cell LPD ( 4 ). We report the case of a boy with massive EBV+ T-cell LPD caused by a novel homozygous ZTBZ24 mutation.…”