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

Bruns, Luzia; Panagiota, Victoria; Hardenberg, Sandra von; Schmidt, Gunnar; Adriawan, Ignatius Ryan; Sogka, Eleni; Hirsch, Stefanie; Ahrenstorf, Gerrit; Witte, Torsten; Schmidt, Reinhold; Atschekzei, Faranaz; Sogkas, Georgios

doi:10.3389/fimmu.2022.742530

Cited by 20 publications

(20 citation statements)

References 64 publications

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“…CVID is a heterogeneous condition and clinical manifestations may vary from increased susceptibility to infections to a variety of inflammatory complications. In addition to GI manifestations, several autoimmune disorders [ 70 ], interstitial lung disease [ 71 ], polyclonal lymphoproliferations [ 72 ], and increased risk of malignancy [ 44 , 73 ] can occur in CVID patients. The hypothetical relationships between these heterogeneous inflammatory manifestations and gut microbioma are largely unknown.…”

Section: Gastrointestinal Manifestations Of Cvidmentioning

confidence: 99%

Is there a role for microbiome-based approach in common variable immunodeficiency?

et al. 2023

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Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.

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Section: Gastrointestinal Manifestations Of Cvidmentioning

confidence: 99%

Is there a role for microbiome-based approach in common variable immunodeficiency?

et al. 2023

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“…The expression of CTLA-4 by sorted Tregs has been performed as described previously [ 25 ]. Briefly, PBMCs, cryopreserved in freezing medium (heat-inactivated FCS, PAN-Biotech; 10% v/v dimethyl sulfoxide, Sigma), were thawed and cultured overnight in complete RPMI medium (at 37°C, 5% CO 2 ).…”

Section: Methodsmentioning

confidence: 99%

CTLA-4 Insufficiency due to a Novel CTLA-4 Deletion, Identified through Copy Number Variation Analysis

Olfe¹,

Hardenberg²,

Hofmann³

et al. 2022

Int Arch Allergy Immunol

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Background: The diagnostic yield of next-generation sequencing (NGS) technologies in the diagnosis of monogenic inborn errors of immunity (IEI) remains limited, rarely exceeding 30%. Monoallelic pathogenic germline variants in cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) result in variable immunodeficiency and immune dysregulation. The genetic diagnosis of CTLA-4 insufficiency can affect follow-up procedures and may lead to consideration of treatment with CTLA-4-Ig. Objectives: The aim of the study was to identify the genetic cause of familial immunodeficiency and immune dysregulation in cases where single nucleotide variant analysis of short-read NGS data yielded no diagnostic result. Methods: Analysis of copy number variants (CNVs) was applied on short-read NGS data. Results: We identified a novel monoallelic deletion-insertion variant in CTLA-4 (c.445_568-544delinsTTTGCGATTG) resulting in familial autoimmunity. This is the second larger scale variant in CTLA-4, which despite consistently reduced expression of CTLA-4 displayed variable expressivity, ranging from typical juvenile idiopathic arthritis to common variable immunodeficiency-like immunodeficiency. Conclusions: Our report suggests the significance of integration of CNV analysis in routine evaluation of NGS, which may increase its diagnostic yield in IEI.

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“…Thus far, the genesis of GC has been attributed to a myriad of factors, including environmental components, lifestyle choices and the presence of Helicobacter pylori infection (Fock, 2014). Furthermore, it is plausible that the interplay between genetic predisposition and immunological elements may contribute to the development of GC (Bruns et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

Correlation of CTLA‐4 polymorphism and the risk of gastric cancer in a Chinese Bai population

Kong

Zheng

Cheng

et al. 2023

Int J Immunogenetics

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Cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA‐4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case–control study. Four single nucleotide polymorphism sites of CTLA‐4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism ‘TC’ genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI): .47 (.35–.63), p < .001]. GC cases with dominant genetic model ‘TC + CC’ had a 47% reduced risk of GC [OR, 95%CI: .53 (.40–.71), p < .001]. Subgroup analyses revealed that the rs733618 ‘TC + CC’ genotype was associated with a lower risk of GC in male patients [OR, 95%CI: .42 (.31–.58), p < .001], those aged ≤60 years old [OR, 95%CI: .27 (.18–.42), p < .001], non‐drinkers [OR, 95%CI: .21 (.13–.33), p < .001], non‐smokers [OR, 95%CI: .38 (.25–.57), p < .001] and individuals without Helicobacter pylori infection [OR, 95%CI: .16 (.10–.26), p < .001]. Further multivariated analyses indicated that individuals with the ‘TC + CC’ rs733618 genotype who were aged ≤60 years old [OR, 95%CI: .42 (.29–.83), p = .032] and had no H. pylori infection [OR, 95%CI: .35 (.28–.76), p = .018] were found to have a protective effect against GC. Additionally, soluble CTLA‐4 were significantly lower in GC patients with ‘TC’ and ‘TC + CC’ genotypes (all p < .05). Our findings suggest that the rs733618 polymorphism of CTLA‐4 gene may play a critical role in the prevention of GC.

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

Cited by 20 publications

References 64 publications

Is there a role for microbiome-based approach in common variable immunodeficiency?

Is there a role for microbiome-based approach in common variable immunodeficiency?

CTLA-4 Insufficiency due to a Novel CTLA-4 Deletion, Identified through Copy Number Variation Analysis

Correlation of CTLA‐4 polymorphism and the risk of gastric cancer in a Chinese Bai population

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