Abstract
Bloom’s syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene. This gene codes for BLM protein, which is a helicase involved in DNA repair. DNA repair is especially important for the development and maturation of the T and B cells. Since BLM is involved in DNA repair, we aimed to study if BLM deficiency affects T and B cell development and especially somatic hypermutation (SHM) and class switch recombination (CSR) processes. Clinical data of six BS patients was collected, and immunoglobulin serum levels were measured at different time points. In addition, we performed immune phenotyping of the B and T cells and analyzed the SHM and CSR in detail by analyzing IGHA and IGHG transcripts using next-generation sequencing. The serum immunoglobulin levels were relatively low, and patients had an increased number of infections. The absolute number of T, B, and NK cells were low but still in the normal range. Remarkably, all BS patients studied had a high percentage (20–80%) of CD4+ and CD8+ effector memory T cells. The process of SHM seems normal; however, the Ig subclass distribution was not normal, since the BS patients had more IGHG1 and IGHG3 transcripts. In conclusion, BS patients have low number of lymphocytes, but the immunodeficiency seems relatively mild since they have no severe or opportunistic infections. Most changes in the B cell development were seen in the CSR process; however, further studies are necessary to elucidate the exact role of BLM in CSR.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Bloom’s syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene located at 15q26
We describe three children (9–12 years) and three adult BS patients (36– 49 years)
We showed in a large number of rearrangements obtained from six BS patients low but normal frequency of somatic hypermutation (SHM) and normal SHM patterns
Summary
Bloom’s syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene located at 15q26. This gene codes for BLM protein, which is a DNA helicase involved in DNA replication and repair. BS is characterized by predisposition to malignancy, prenatal growth retardation, gastro-esophageal reflux, café-au-lait spots, characteristic butterfly-shaped erythema, and immunodeficiency [1, 2]. The immunodeficiency is characterized by low serum immunoglobulins and different infections. Otitis media is a very common infection among BS patients, especially in children. Up to 20% of the BS patients had pneumonia. [1] the pathophysiology behind the immunodeficiency in BS has not yet been elucidated Up to 20% of the BS patients had pneumonia. [1] the pathophysiology behind the immunodeficiency in BS has not yet been elucidated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
