In vitro chromosomal radiosensitivity in patients with common variable immunodeficiency

Mahmoodi, Majid; Abolhassani, Hassan; Mozdarani, Hossein; Rezaei, Nima; Azizi, Gholamreza; Yazdani, Reza; Farzanfar, Farideh; Rafiemanesh, Hosein; Mohagheghi, Mohammad Ali; Divsalar, Kouros; Kalmarzi, Rasoul Nasiri; Ramyar, Asghar; Aghamohammadi, Asghar

doi:10.5114/ceji.2018.77385

Cited by 17 publications

(15 citation statements)

References 35 publications

(33 reference statements)

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“…The latter is in accordance with the previously reported high frequency of genetic variation in DNA repair genes in CVID (57,58). A genetic background affecting DNA repair would be in line with studies demonstrating chromosomal radiosensitivity (59,60) and DSR defects in CVID (58) as well as with the identified higher prevalence of NMSC, whose key risk factor is the ultraviolet radiation through its DNA damage-inducing potential (61).…”

Section: Discussionsupporting

confidence: 91%

Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

et al. 2022

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ObjectiveThe aim of this study was to investigate the prevalence of cancer and associating clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID).MethodsIn this retrospective monocenter cohort study, we estimated the standardized incidence ratio (SIR) for different forms of cancer diagnosed in CVID patients. Furthermore, we evaluated the likely association of infectious and non-infectious CVID-related phenotypes with the diagnosis of cancer by calculation of the odds ratio. The genetic background of CVID in patients with cancer was evaluated with sequential targeted next-generation sequencing (tNGS) and whole-exome sequencing (WES). Patients’ family history and WES data were evaluated for genetic predisposition to cancer.ResultsA total of 27/219 patients (12.3%) were diagnosed with at least one type of cancer. Most common types of cancer were gastric cancer (SIR: 16.5), non-melanoma skin cancer (NMSC) (SIR: 12.7), and non-Hodgkin lymphoma (NHL) (SIR: 12.2). Immune dysregulation manifesting as arthritis, atrophic gastritis, or interstitial lung disease (ILD) was associated with the diagnosis of cancer. Furthermore, diagnosis of NMSC associated with the diagnosis of an alternative type of cancer. Studied immunological parameters did not display any significant difference between patients with cancer and those without. tNGS and/or WES yielded a definite or likely genetic diagnosis in 11.1% of CVID patients with cancer. Based on identified variants in cancer-associated genes, the types of diagnosed cancers, and family history data, 14.3% of studied patients may have a likely genetic susceptibility to cancer, falling under a known hereditary cancer syndrome.ConclusionsGastric cancer, NMSC, and NHL are the most frequent CVID-associated types of cancer. Manifestations of immune dysregulation, such as arthritis and ILD, were identified as risk factors of malignancy in CVID, whereas studied immunological parameters or the identification of a monogenic form of CVID appears to have a limited role in the evaluation of cancer risk in CVID.

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Section: Discussionsupporting

confidence: 91%

Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

et al. 2022

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“…Diagnosis of the patients was based on the European Society for Immunodeficiency (ESID) guideline (15), including ataxia and at least two of the following: oculocutaneous telangiectasia, elevated AFP, lymphocyte AT karyotype with translocation chromosome 7:14, and cerebellar hypoplasia on magnetic resonance imaging (MRI). The wholeexome sequencing and confirmatory Sanger sequencing method were carried out according to a pipeline published previously (16)(17)(18)(19)(20), and a radiosensitivity test using G0 and G2 phase assays on phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes were performed (21).…”

Section: Patients and Clinical Evaluationmentioning

confidence: 99%

Atypical Ataxia Presentation in Variant Ataxia Telangiectasia: Iranian Case-Series and Review of the Literature

et al. 2022

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Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype with an increased risk of cancer. Variant AT patients present with milder phenotype or atypical form of classical symptoms causing under- or mis- diagnosis. Although missense mutations are more frequent, an atypical presentation can be associated with deleterious mutations due to unknown modifying factors.

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“…The same phenomenon can be present in other entities of PAD with low IgA levels including congenital agammaglobulinemia and IgA deficiency (62,(66)(67)(68). Of note, a minority of CVID patients can present chromosomal radiosensitivity due to disruption of DNA repair machinery and must be considered for tumorigenesis due to genome instability and regular screening for cancer and avoidance of malignancy triggers must be added to their routine management (69,70).…”

Section: Tumor-promoting Inflammationmentioning

confidence: 81%

Hallmarks of Cancers: Primary Antibody Deficiency Versus Other Inborn Errors of Immunity

et al. 2021

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Inborn Errors of Immunity (IEI) comprise more than 450 inherited diseases, from which selected patients manifest a frequent and early incidence of malignancies, mainly lymphoma and leukemia. Primary antibody deficiency (PAD) is the most common form of IEI with the highest proportion of malignant cases. In this review, we aimed to compare the oncologic hallmarks and the molecular defects underlying PAD with other IEI entities to dissect the impact of avoiding immune destruction, genome instability, and mutation, enabling replicative immortality, tumor-promoting inflammation, resisting cell death, sustaining proliferative signaling, evading growth suppressors, deregulating cellular energetics, inducing angiogenesis, and activating invasion and metastasis in these groups of patients. Moreover, some of the most promising approaches that could be clinically tested in both PAD and IEI patients were discussed.

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In vitro chromosomal radiosensitivity in patients with common variable immunodeficiency

Cited by 17 publications

References 35 publications

Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

Atypical Ataxia Presentation in Variant Ataxia Telangiectasia: Iranian Case-Series and Review of the Literature

Hallmarks of Cancers: Primary Antibody Deficiency Versus Other Inborn Errors of Immunity

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