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

DISEASES - Tập 7 Số 2 - Trang 34
Georgios Sogkas1, Natalia Dubrowinskaja1, Anke K. Bergmann2, Jana Lentes2, Tim Ripperger2, Mykola Fedchenko3, Diana Ernst1, Alexandra Dopfer‐Jablonka1, Robert Geffers4, Ulrich Baumann5, Reinhold Schmidt1, Faranaz Atschekzei1
1Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany
2Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany
3Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany
4Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
5Department of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, 30625 Hannover, Germany

Tóm tắt

Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c.1222 T>G, p. (Cys408Gly)). Immune deficiency in these patients ranged from late-onset combined immunodeficiency (CID) with severe respiratory tract infections and recurrent shingles to asymptomatic selective antibody deficiency. Evident clinical heterogeneity manifested despite a common genetic background, suggesting the pathogenic relevance of epigenetic modification. Immunological follow-up reveals a previously unidentified gradual depletion of B and CD4+ T cells in all three presented patients with transition of a common variable immunodeficiency (CVID)-like disease to late-onset-CID in one of them. Considering all previously published cases with ICF2, we identify inadequate antibody responses to vaccines and reduction in CD27+ memory B cells as prevalent immunological traits. High mortality among ICF2 patients (20%) together with the progressive course of immunodeficiency suggest that hematopoietic stem cell transplantation (HSCT) should be considered as a treatment option in due time.

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Tài liệu tham khảo

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Tập 7 Số 2

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